2025 POSTER ABSTRACTS
Poster presenters will be available for questions during their assigned
days and times shown below in the Statler Room:
Thursday, October 23
11:00 – 11:30 AM and 12:30 – 1:00 PM
Friday, October 24
12:00 – 12:30 PM and 1:30 – 2:00 PM
Poster #
Title
01
Predicting Future Cardiovascular events by Lipid Core Burden index (LCBI)
Farrukh Malik
National Institute of Cardiovascular Diseases, Pakistan
Background:
Vulnerable coronary plaques, particularly those rich in lipid content, are key contributors to the onset of acute coronary syndromes. The Lipid Core Burden Index (LCBI) has gained attention as a promising imaging biomarker for detecting patients who may be at increased risk of experiencing future major adverse cardiovascular events (MACE). Near-infrared spectroscopy (NIRS) is a novel imaging technique that detects plaques with high lipid content, which is a critical indicator of plaque vulnerability.
Purpose:
This study evaluates the prognostic utility of NIRS-derived LCBI in predicting MACE in patients undergoing coronary angiography.
Methods:
We conducted a prospective study at National Institute of Cardiovascular diseases involving 100 patients undergoing NIRS-IVUS imaging during clinically indicated coronary catheterization. The primary endpoint was a composite of MACE (defined as cardiac death, myocardial infarction, or unplanned revascularization) at 12 months. Non-culprit lesions were imaged using Makoto NIRS-IVUS, and the highest LCBI was recorded for each patient. Patients were stratified into two groups based on LCBI values: high-risk (≥400) and low-risk (<400). Event rates were compared using Kaplan-Meier analysis, and Cox proportional hazards modeling was used to assess the independent predictive value of LCBI.
Results:
Among 100 patients (mean age 64±9 years; 72% male), 23 % had a non-culprit lesion with LCBI ≥400. At 12 month follow-up, the incidence of MACE was significantly higher in the high-LCBI group compared to the low-LCBI group (11.2% vs. 4.2%, p<0.001). After adjusting for traditional risk factors and angiographic stenosis severity, LCBI ≥400 remained an independent predictor of MACE (adjusted HR 3.6; 95% CI 2.1-6.2; p<0.001). Notably, most events occurred at sites with <70% angiographic stenosis, highlighting the added value of plaque characterization beyond lumen assessment.
Conclusions:
NIRS-derived LCBI is a robust and independent predictor of future MACE in patients undergoing coronary angiography. An LCBI threshold of ≥400 identifies high-risk plaques in non-culprit segments, often missed by angiography alone. Incorporating NIRS imaging into routine clinical practice may enhance risk stratification and guide targeted preventive therapies in patients with coronary artery disease.
Disclosures:
Nothing to disclose by any authors.
02
The NHHR index as a predictor of cardiovascular and all-cause mortality in patients with metabolic dysfunction-associated steaotic liver disease: evidence from NHANES III
Yu Zongliang a, b, Yu Binyang a, b, Li Lingling b, Yang Qiaoning b*, Gao Rui b*
a Beijing University of Chinese Medicine, Beijing, China
b Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
Background:
The present investigation introduces the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a new composition measure for assessing the risk of certain disorders. However, its relationship with mortality risk, particularly in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), warrants comprehensive investigation.
Purpose:
To explore the association between a novel lipid marker, NHHR, and cardiovascular death in patients with metabolic dysfunction-associated steatotic liver disease.
Methods:
This investigation encompassed 3,753 adult MASLD patients from NHANES III, with mortality data sourced from the National Death Index. To sightsee the connection between NHHR and mortality outcomes, we utilized weighted multivariate Cox proportional hazards models and restricted cubic splines (RCS). Segmented Cox models were utilized to discern hazard ratios around the identified inflection point. Furthermore, subgroup analyses were executed to evaluate the sensitivity and effects of interactions.
Results:
During the follow-up period, the group had 1,633 deaths, of which 455 were ascribed to cardiovascular disease. Following the adjustment for multiple covariates, the hazard ratios for all-cause mortality across the NHHR quartiles were found to be 1.00, 0.95, 1.14, and 1.27, respectively. Correspondingly, the hazard ratios for cardiovascular death were 1.00, 0.90, 1.51, and 1.73. The inclusion of RCS in the Cox model demonstrated a significant U-shaped correlation between NHHR and mortality from all causes, with a specific point of inflection at 3.54. Below this threshold, every incremental unit elevation in NHHR corresponded with a 2% decrease in all-cause mortality risk, whereas surpassing the inflection resulted in a 6% increase in risk per unit elevation in NHHR. Furthermore, a linear association was evident between NHHR and cardiovascular mortality, indicating a 14% increase in cardiovascular death risk for every unit rise in NHHR. Notably, the elevated risk of both all-cause and cardiovascular mortality among individuals under 60, women, and those classified as overweight with higher NHHR underscores the necessity for closer monitoring of this index in these populations.
Conclusions:
The NHHR index exhibits a distinct U-shaped correlation with mortality from all causes and a direct linear relationship with cardiovascular mortality. Regular observing of NHHR may offer valuable insights into mortality risk evaluation in MASLD patients.
Disclosures:
The study was financially supported by the Project of Integrated Platform for Clinical Research of Traditional Chinese Medicine of Xiyuan Hospital, China Academy of Chinese Medical Sciences (XYZX0405-32).
03
Peculiarities in the vitamin D-homocysteine-liver axis in men as potential contributors to the higher prevalence of metabolic dysfunction-associated fatty liver disease
S.Ljubic1, A. Jazbec2, I. Antal1, M. Tomic3, T. Bulum1, D. Rahelic4
1Department of Diabetes and Metabolic Diseases, Vuk Vrhovac University Clinic, Merkur Clinical Hospital, University of Zagreb, Zagreb, Croatia, 2University of Zagreb, Laboratory for design of experiment and statistical data analysis, Zagreb, Croatia, 3Department of Ophthalmology, Vuk Vrhovac University Clinic, Merkur Clinical Hospital, , Zagreb, Croatia, 4Merkur Clinical Hospital, Vuk Vrhovac University Clinic, University of Zagreb, Catholic University of Croatia School of Medicine, Zagreb, Croatia.
Background:
Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of renal and coronary artery disease. Vitamin D enhances the mRNA and protein expression of methionine synthase, thereby lowering the risk of hyperhomocysteinemia
Purpose:
An impact of vitamin D on the onset of metabolic dysfunction-associated fatty liver disease (MAFLD) has also been observed, with MAFLD being more frequently present in men.
Methods:
Hcy, 25-hydroxyvitamin D (25(OH)D), vitamin B12, lipids, renal function parameters, and several other diabetes-related markers, including the lipid accumulation product (LAP), a novel biomarker of central lipid accumulation related to the risk of cardiovascular disease, and MAFLD were tested in type 2 diabetic patients (type 2 DM), separately for women and men. LAP was calculated using the formula: male LAP = [waist (cm) − 65] × TG concentration (mmol/l) and female LAP = [waist (cm) − 58] × TG concentration (mmol/l).
Results:
Descriptive statistics for women; 25(OH)D 56.76±16.72; Hcy 19.22±11.77; LAP 84.70±51.14; estimated glomerular filtration rate (eGFR) 87.48±21.66 and men; 25(OH)D 58.43±18.43; Hcy 16.98±8.72; LAP 72.94±62.41; eGFR 84.17±20.89. There was no statistically significant difference for 25(OH)D (p=0.7148), Hcy (p=0.3748), LAP (p=0.4348) and eGFR (p=0.5389) by gender. A negative correlation was determined between 25(OH)D and Hcy. In women this correlation is statically significant (rw=-0.574, p=0.005; rm=-0.085, p=0.565). A negative correlation was also determined in women between 25(OH)D and LAP (rw=-0.204, p=0.350; rm=-0.324, p=0.0247). Hcy correlated significantly with eGFR in women (rw=-0.684. p<0.001) and in men (rm=-0.405, p=0.004). An increase in Hcy is associated with decrease in eGFR levels. The correlation between eGFR and 25(OH)D is positive and statistically significant in women (rw=0.427, p=0.042) and in men (rm=0.337, p=0.019). Univariate linear regression in women pointed at Hcy (R2=0.329) and eGFR (R2=0.182), but not at LAP (R2=0.042) as significant variables in prediction of 25(OH)D levels. In men eGFR (R2=0.113) and LAP (R2=0.105) were statistically significant in the prediction of 25(OH)D levels, but not Hcy (R2=0.007). This is consistent with the observation about a lack of correlation between Hcy and 25(OH)D in men.
Conclusions:
In our study, no difference in vitamin D levels was observed between men and women. In men there was no significant correlation between vitamin D and Hcy, and vitamin D and LAP. Hcy was not among the predictors of vitamin D in men. Peculiarities in the vitamin D – Hcy – LAP axis in men compared to women could be among the reasons for the more common onset of MAFLD in men compared to women, with possible explanations involving sex steroids, methionine catabolism, or inflammation.
Disclosures:
Nothing to disclose by any authors.
04
Clinical and Methodological Characteristics Analysis and Construction Recommendations of Inclusion and Exclusion Criteria in Clinical Study Protocols: A Case Study of Acute Myocardial Infarction with Type 2 Diabetes Mellitus
Guan Xinmiao, Fei Yutong
Background:
Inclusion and exclusion criteria define who can or cannot participate in clinical trials, based on characteristics such as age, health status, comorbidities, and physiological parameters. Their primary purpose is to protect participants by balancing potential risks and benefits. Well-designed criteria enhance internal validity, safety, and feasibility while ensuring ethical and scientific integrity. Regulatory bodies like the FDA recommend considering disease characteristics, intervention features, and recruitment feasibility. However, in China, standardized guidance remains limited, often leading to vague or incomplete criteria. Methodologically, a structured, goal-oriented framework can improve study transparency, reproducibility, and external validity.
Purpose:
This study systematically reviews and analyzes the design of inclusion and exclusion criteria in clinical studies involving patients with acute myocardial infarction combined with type 2 diabetes mellitus (AMI-T2DM). From the perspectives of real-world studies (RWS) and randomized controlled trials (RCTs), it summarizes the design characteristics and methodological elements of existing research. The goal is to provide methodological guidance for researchers conducting future studies related to AMI-T2DM.
Methods:
A comprehensive literature search was conducted in the following databases: CNKI, VIP, Wanfang, Embase, PubMed, and the Cochrane Library, covering records from the inception of each database up to November 9, 2024. Two independent researchers screened the retrieved studies and extracted relevant data, including fundamental study characteristics and the inclusion and exclusion criteria.
The analysis framework for diagnostic and eligibility criteria was refined from the project team’s existing “Risk Identification Checklist for Clinical Study Protocols.” This optimized evaluation tool comprised fifteen items, covering both clinical applicability and methodological rigor. The items included: Western medical diagnostic basis, participant age, sex, etiology and disease duration, comorbidities, treatment history, underlying conditions, outcome confounding factors, subgroup characteristic definition, data completeness, diagnostic and treatment process, drug contraindications and safety, ethical procedures, and duration of follow-up.
The inclusion and exclusion criteria were assessed along two principal dimensions-clinical applicability and methodological soundness-according to this structured framework.
Results:
A total of 81 studies were included: 19 in English (14 real-world studies [RWS] and 5 randomized controlled trials [RCTs]) and 62 in Chinese (30 RWS and 32 RCTs). The majority of studies specified inclusion and exclusion criteria, often referencing diagnostic guidelines issued by international organizations or professional societies. However, there were substantial discrepancies in implementation details, clause structure, and technical specifications.
In RWS, some studies relied solely on ICD codes or custom-defined diagnostic standards, while several RCTs lacked clear sources for diagnostic criteria or had missing items. Most studies did not explicitly list diagnostic components or specify quantitative thresholds, and the expression of criteria generally lacked a structured design.
Common issues identified in the inclusion and exclusion criteria included: inconsistent hierarchical structuring, unclear boundaries of eligibility conditions, and exclusion logic that was misaligned with study objectives. Furthermore, many studies lacked defined or clearly stated decision rules; terminology was often vague or generalized, and the criteria lacked consistency and operational clarity.
Notably, some studies introduced selection conditions after the intervention phase, a methodological flaw that limited the population at the analytical level. This design bias compromised the representativeness of the sample and weakened the interpretability of the study findings.
Conclusions:
The inclusion and exclusion criteria in studies of AMI combined with T2DM can be categorized into four core design elements: (1) defining the disease state, (2) standardizing intervention or exposure, (3) controlling comorbidities and underlying conditions, and (4) ensuring research quality. These elements aim to enhance clinical homogeneity among study participants, reduce variability in intervention pathways, control outcome heterogeneity, and improve the feasibility of study implementation.
RCTs tend to adopt more stringent eligibility criteria, prioritizing internal validity and experimental controllability. In contrast, RWS often apply relatively lenient criteria, placing greater emphasis on external validity and real-world applicability. Despite these differences, both study types generally follow a similar logical structure; the primary distinctions lie in the degree of control and the conditions under which the criteria are implemented.
Disclosures:
Nothing to disclose by any authors.
05
Insulin Resistance Mediates the Link Between Dietary Inflammatory Index and Advanced Cardiovascular-Kidney-Metabolic Syndrome Stages: NHANES 2007-2018
Hongzhao You; Ying Xiao; Jiansong Yuan; Weixian Yang
Background:
Cardiovascular-Kidney-Metabolic (CKM) syndrome represents a continuum of progressive dysfunction involving metabolic, renal, and cardiovascular systems, and is classified into five distinct stages. Individuals in advanced stages face substantially elevated risks of all-cause and cardiovascular-related mortality. Emerging evidence highlights chronic low-grade inflammation and insulin resistance (IR) as pivotal drivers of CKM progression. The Dietary Inflammatory Index (DII), a validated tool to quantify the inflammatory potential of diet, may play a role in CKM progression; however, its association with CKM staging remain unexplored.
Purpose:
The purpose of this study was to investigate whether dietary inflammatory potential, as assessed by the DII, is associated with progression to advanced stages of CKM syndrome in U.S. adults, and to explore whether IR mediates this relationship.
Methods:
We conducted a cross-sectional analysis using data from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning 2007-2018. DII scores were calculated from 24-hour dietary recall data. Advanced CKM was defined as stage 3 or 4 according to American Heart Association guidelines, representing individuals with established or high-risk cardiovascular disease. IR was estimated using the HOMA-IR index, calculated by fasting plasma glucose (mmol/L) × fasting insulin (mIU/L) / 22.5. Statistical analyses were performed after adjusting for covariates, including age, sex, race, education level, smoking status, physical activity, and total energy intake.
Results:
Among 12,993 eligible participants, 2,167 (16.68%) were classified as having advanced CKM stages. The weighted mean DII was 0.87 ± 2.04, and the weighted median HOMA-IR was 2.51 (1.51-4.32). Participants in advanced CKM stages exhibited significantly higher DII scores (1.20 ± 2.03 vs. 0.82 ± 2.03, P<0.001) and HOMA-IR levels (3.18 [1.77-5.70] vs. 2.43 [1.48-4.15], P < 0.001) compared to those in earlier stages (0-2). Weighted logistic analysis showed that individuals in the highest DII quartile (≥2.42) had a significantly increased risk of advanced CKM (adjusted odds ratio: 1.39; 95% confidence interval: 1.08-1.78; P = 0.010) compared to those in the lowest quartile (<0.69). Weighted Restricted cubic spline models demonstrated a linear positive association between DII and advanced CKM stages (Poverall < 0.001; Pnonlinear = 0.12). Mediation analysis indicated that TyG accounted for 45.5% of the positive association between DII and advanced CKM stages.
Conclusions:
A diet with higher inflammatory potential, reflected by elevated DII scores, is significantly associated with progression to advanced CKM stages. This relationship is partially mediated by IR. These findings underscore the potential of DII as a modifiable risk factor for CKM prevention and highlight the importance of anti-inflammatory dietary strategies in managing cardiometabolic health.
Disclosures:
Nothing to disclose by any authors.
06
Efficacy of empagliflozin in heart failure with preserved ejection fraction is related to the presence of echocardiographic features of diastolic dysfunction in the EMPEROR-Preserved trial
- Andrew J. Coats, 2. Javed Butler, 3. Hendrik S. Zimmet, 4. Stefan D. Anker
- Heart Research Institute, Newtown, Sydney, NSW, Australia.
- Baylor Scott and White Research Institute, Dallas, TX, United States.
- Cardiac Clinical Sciences Institute, Epworth, Melbourne, VIC, Australia
- German Heart Center Charité, Berlin, Germany
Background:
Efficacy of empagliflozin in patients with heart failure (HF) is seen across the left ventricular ejection fraction (LVEF) spectrum and in multiple clinical subgroups, with diverse mechanisms of action.
Purpose:
To investigate whether diastolic dysfunction (DD) in patients with HF with preserved ejection fraction (HFpEF) predicted empagliflozin response in the EMPEROR-Preserved trial (NCT03057951).
Methods:
DD was defined as left atrial volume index ≥34 mL/m2, early mitral inflow velocity/early diastolic mitral annular velocity ratio ≥13 or left ventricular mass index >115 (males) or >95 (females). Three categories of patients were defined with 0, 1 or ≥2 DD criteria. We report the impact of baseline DD on response to empagliflozin therapy and adverse effects. Analyses were performed using the intention-to-treat principle. For time-to-first-event analyses, differences in treatment effects across the three DD categories were assessed by a Cox proportional hazards model, with pre-specified covariates of age, gender, region, diabetes, LVEF, and estimated glomerular filtration rate (eGFR). Total events were assessed using a joint frailty model, with cardiovascular (CV) death as a competing risk.
Results:
Of the 5988 participants, 3766 (63%) had no baseline DD, 1619 (27%) had one measure and 603 (10%) had ≥2. The percentage of males decreased with increasing DD category (57.2% for none, 54.2% for one and 46.6% for ≥2, p <0.0001). Race, ethnicity, age, HR, diastolic blood pressure, left ventricular ejection fraction, ischemia etiology, body weight and estimated glomerular filtration rate were also associated with DD categories. A progressive treatment effect across DD categories was seen for time to hospitalization for HF (HHF) or CV death (hazard ratio [HR]: 0.91 for none, 0.64 for one and 0.49 for ≥2; interaction p-value 0.0014), and total number of HHF (HR: 0.95 for none, 0.52 for one and 0.29 for ≥2). In the responder analysis, a ≥10-point improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) at Week 52 showed a consistent treatment-induced change across DD categories (interaction p-value 0.92). The safety profile was consistent across DD categories.
Conclusions:
Baseline echocardiographic diastolic dysfunction predicted improved clinical response to empagliflozin in a graded fashion, suggesting the mode of action may target specific changes in diastolic performance.
Disclosures:
AJC has received consulting fees from Actimed, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, and Respicardia; has received payment or honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards, Eli Lilly, Menarini, Novartis, Servier, Vifor, and Viatris; and has participated on a data safety monitoring board or advisory board from Impulse Dynamics.
JB is a consultant to Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Eli Lilly, Faraday, Idorsia, Imbria, Impulse Dynamics, Innolife, Intellia, Inventiva, Levator, Lexicon, Mankind, Medtronic, Merck, New Amsterdam, Novartis, NovoNordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, SC Pharma, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromic, Vera, Zoll.
HSZ – Honoraria: Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Lilly, Menarini, Novartis, Novo Nordisk, Pfizer, Servier, Vifor, Zoll. Sponsorship: Astra Zeneca, Boehringer Ingelheim, MSD, Menarini, Servier. Site Principal Investigator: AMGEN, George Clinical, Luitpold/Vifor, Boehringer Ingelheim, V-Wave Ltd. Advisory Board Membership: Novartis, Otsuka, Vifor
SDA reports grants and personal fees from Abbott Vascular and Vifor, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Cytokinetics, Edwards, Faraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Novartis, Occlutech, Pfizer, Repairon, Sensible Medical, Servier, Vectorious, and V-Wave.
The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the abstract. Jonathon Gibbs, of Envision Ignite, an Envision Medical Communications agency, a part of Envision Pharma Group, provided editorial support, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI) and Lilly USA, LLC. BIPI was given the opportunity to review the abstract for medical and scientific accuracy, as well as intellectual property considerations. The study was supported and funded by the Boehringer Ingelheim & Eli Lilly and Company Alliance.
07
Effects of telehealth coaching on health-promoting behaviours in middle-aged adults with cardiometabolic risk: A randomised controlled trial
Zoe Ching-man Kwok1, Hon-lon Tam1, Helen Yue-lai Chan1
1The Nethersole School of Nursing, Faculty of Medicine, the Chinese University of Hong Kong
Background:
Cardiometabolic disease remains the leading causes of global disability-adjusted life-years among middle-aged population. Modifiable cardiometabolic risk factors, such as physical inactivity, unhealthy diet, stress and poor sleep, are common among middle-aged adults. Proactive measures are lacking in primary care because existing lifestyle modification interventions are for secondary care. Health coaching, which promotes behavioural change through enlightenment and empowerment, has been widely adopted and was effective in chronic disease management, but its effect on cardiometabolic health in primary care was unclear. Telehealth coaching significantly improves health outcomes, such as weight loss and glycemic control, in facilitating cardiometabolic risk reduction. Our systematic review found telehealth coaching was acceptable by middle-aged adults in primary care. Therefore, a telehealth coaching programme was developed for middle-aged population at risk of developing cardiometabolic disease.
Purpose:
To test the effects of a telehealth coaching programme among middle-aged adults with moderate-to-high cardiometabolic risk.
Methods:
This was a two-arm, parallel, assessor-blinded, multisite randomised controlled trial. Adults aged 40 – 60 with moderate-to-high cardiometabolic risk, i.e. non-laboratory INTERHEART risk score (IHRS) ≥ 10, were recruited from local district health centres and via social media. They were randomised into intervention or control group in a 1:1 ratio. All participants received the results of outcome assessment, while the participants in the intervention group additionally received four monthly, individual, nurse-facilitated telehealth coaching sessions over three months. Participants in the control group were recommended to seek health information from local government website as usual care. Outcome measures included health-promoting behaviours, self-efficacy, cardiometabolic risk, psychological distress, sleep quality, physical activity level, and physiological parameters (blood pressure, pulse, body mass index (BMI), waist-hip ratio (WHR), and blood glucose, lipid and urate). Outcome measures assessments were conducted at baseline (T0), three-month (T1) and six-month (T2) after group allocation. Generalized estimating equations (GEE), significance level of 0.05 and two-tailed test were used for data analysis. All analyses were based on the intention-to-treat principle. This trial was registered at ClinicalTrials.gov (identifier: NCT05284162). Ethical approval was sought from the Chinese University of Hong Kong-NTEC Research Ethics Committee (CRECT RefNo. 2021.257).
Results:
A total of 202 participants were recruited with a mean age of 53.3 years (SD 7.33). The mean telehealth coaching attendance rate was 90.1%. Compared with the control group, participants receiving telehealth coaching demonstrated a significantly greater improvement in health-promoting behaviours towards physical activity at T2 (β = 0.170, 95% CI [0.039, 0.301], p = .011) and a greater reduction in diastolic blood pressure at T1 (β = −2.618, 95% CI [−5.206, −0.030], p = .047). Participants in the intervention group also demonstrated significant improvements in other health-promoting behaviours, including health responsibility, nutrition, physical activity, and stress management, self-efficacy, cardiometabolic risk, depression, anxiety, stress level, and sleep quality, at both T1 and T2 compared with T0. However, the between-group differences in these outcome measures did not reach statistical significance.
Conclusions:
A telehealth coaching programme was developed and found to have some effects on improving health-promoting behaviours and cardiometabolic health outcomes of middle-aged adults with cardiometabolic risk. This study revealed the potential of health coaching to be incorporated into primary care for cardiometabolic disease prevention. The study findings also inform future research exploring the optimal dose and long-term effects of health coaching in primary care.
Disclosures:
Nothing to disclose by any authors.
08
Silencing APOC3: A Novel Olezarsen Therapy in Familial Chylomycronemia Syndrome
Karen N. Yelton Torres, Milton Rivera Valentin, Jose M. Garcia Mateo, Karen Sanabria
Damas Hospital Internal Medicine Residency Program, Ponce, Puerto Rico
Background:
Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia due to impaired clearance of chylomicrons. Most cases result from biallelic pathogenic variants in genes essential for lipolysis, most commonly LPL, but also APOC2, APOA5, GPIHBP1, or LMF1. APOA5 is thought to stabilize the LPL-lipoprotein complex, and rare mutations that abolish apoA-V function lead to classic FCS with severely impaired lipolysis. Patients present with fasting hypertriglyceridemia (>885 mg/dL), recurrent pancreatitis, eruptive xanthomas, and lipemia retinalis. Heterozygous carriers may exhibit variable phenotypes depending on environmental and genetic modifiers. The condition is frequently underrecognized due to diverse clinical presentations including xanthomas, hypercholesterolemia, thrombocytopenia, or hemolytic anemia, sometimes leading to misdiagnosis. Epidemiologic data show FCS remains exceedingly rare across populations, including Latinos, with prevalence estimates of <0.05% among those with triglycerides >500 mg/dL. Early recognition is critical since conventional lipid-lowering therapies such as fibrates often prove ineffective, given their reliance on upregulating functional LPL. Novel therapies such as antisense oligonucleotides targeting APOC3 offer promising new options by enhancing triglyceride clearance. Timely diagnosis and intervention are essential to prevent complications and improve quality of life.
Purpose:
The purpose of this case report is to highlight the diagnostic process, genetic findings, and therapeutic management of a Hispanic patient with Familial Chylomicronemia Syndrome. This case is noteworthy because it illustrates the presentation of FCS in a Puerto Rican female, an ethnic group where this condition is rarely reported, underscoring the importance of genetic evaluation in patients with persistent hypertriglyceridemia. It also demonstrates the therapeutic potential of olezarsen, an antisense oligonucleotide targeting APOC3, in reducing triglyceride levels in patients with genetically confirmed FCS who exhibit poor response to conventional therapies such as fibrates and omega-3 fatty acids. By presenting this case, we aim to increase awareness of FCS in underrepresented populations, emphasize the utility of genetic testing for accurate diagnosis, and provide clinical evidence supporting the integration of novel targeted therapies into practice for effective triglyceride reduction and prevention of recurrent pancreatitis.
Methods:
We report the case of a 37-year-old Puerto Rican female referred to endocrinology clinic by her cardiologist for evaluation of persistent hypertriglyceridemia since childhood. She was managed with fenofibrate 160 mg daily and omega-3 fatty acids 1 g daily. Family history was significant for hypertriglyceridemia and pancreatitis in her mother, without premature cardiovascular disease. Physical exam revealed no eruptive xanthomas or lipemia retinalis. Laboratory evaluation showed total cholesterol 283 mg/dL and triglycerides 1117 mg/dL, with normal liver function tests, hematology, and platelets. ApoB levels were elevated at 114 mg/dL. A genetic panel identified a heterozygous mutation in APOA5 (c.56C>G, p.(Ser19Trp), confirming the diagnosis of FCS. Nutritional counseling and a very low-fat diet (<20 g/day) were initiated. Pharmacologic management included olezarsen 80 mg subcutaneous monthly. Olezarsen, exerts its effect by binding APOC3 mRNA, reducing APOC3 protein synthesis, thereby disinhibiting LPL and improving triglyceride clearance. Follow-up lipid panels were obtained at baseline and after therapy initiation.
Results:
At baseline, the patient’s triglycerides were 1117 mg/dL, despite ongoing treatment with fenofibrate and omega-3 fatty acids. ApoB was elevated at 114 mg/dL. Genetic testing confirmed heterozygosity for an APOA5 pathogenic variant. Following diagnosis, the patient was counseled on strict dietary fat restriction (<20 g/day) and initiated on olezarsen 80 mg monthly. After one week of therapy, lipid profile demonstrated improvement with triglycerides reduced to 749 mg/dL, total cholesterol 319 mg/dL, and HDL-C 43 mg/dL. This represented approximately a 70% reduction in triglyceride levels within the first month, surpassing reductions reported in the BALANCE trial, where olezarsen demonstrated significant triglyceride lowering in patients with hypertriglyceridemia. Importantly, the patient reported no adverse effects during treatment initiation, and adherence was facilitated by the once-monthly injection schedule. This outcome underscores the therapeutic potential of targeting APOC3 in patients with genetically mediated chylomicronemia syndromes, even when heterozygous variants are involved. Conventional pharmacotherapies, such as fibrates, are largely ineffective in this population due to their reliance on functional LPL activity. Olezarsen, by directly downregulating APOC3, bypasses the genetic impairment and restores triglyceride metabolism, offering a targeted approach. The magnitude of triglyceride reduction observed in this case highlights the role of novel therapies in managing rare genetic dyslipidemias.
Conclusions:
This case illustrates the clinical presentation and management of Familial Chylomicronemia Syndrome in a Hispanic patient, emphasizing the importance of genetic testing in populations where this condition is rarely reported. It demonstrates that even heterozygous APOA5 variants can result in clinically significant hypertriglyceridemia and pancreatitis risk, necessitating careful diagnostic workup. The dramatic triglyceride reduction achieved with olezarsen supports its role as a highly effective therapeutic option in FCS, particularly in cases refractory to standard therapies such as fibrates and omega-3 fatty acids. For clinical practice, this case highlights the need for heightened awareness among clinicians to consider genetic dyslipidemias in young patients with severe, persistent hypertriglyceridemia. For future research, larger studies are warranted to evaluate olezarsen efficacy across diverse populations and genetic variants, including Hispanic cohorts, and to assess long-term cardiovascular outcomes. Expanding genetic screening and improving access to novel lipid-lowering therapies will be crucial to reducing morbidity and improving quality of life for patients with FCS worldwide.
Disclosures:
Nothing to disclose by any authors.
09
Free fatty acids: independent predictors of long-term adverse cardiovascular outcomes in heart failure patients
Guang-zhi Liao, Hui-hui Liu, Yu-hui Zhang, Jian Zhang
Background:
The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear.
Purpose:
This study aimed to investigate the prognostic significance of FFA in patients with heart failure.
Methods:
A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index).
Results:
Among the 4,109 HF patients, FFA levels exceeding 0.4-0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11-1.58) for CV death & HHP, 1.45 (95% CI: 1.16-1.82) for CV death, and 1.39 (95% CI: 1.15-1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01).
Conclusions:
Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients.
Disclosures:
Nothing to disclose by any authors.
10
High medication burden in individuals with difficult-to-control type 2 diabetes: clinical characteristics from the CATALYST study
Richard Pratley,1 Ralph A. DeFronzo,2 John Buse,3 Bradley Eilerman,4 Vivian Fonseca,5 Yehuda Handelsman,6 John C. Parker,7 Julio Rosenstock,8 Guillermo Umpierrez,9 Daniel Einhorn10
1AdventHealth Translational Research Institute, Orlando, FL; 2University of Texas Health Science Center, San Antonio, TX; 3University of North Carolina School of Medicine, Chapel Hill, NC; 4St. Elizabeth Physicians, Covington, KY; 5Tulane University, New Orleans, LA; 6Metabolic Institute of America, Tarzana, CA; 7Accellacare Research/Wilmington Health, Wilmington, NC; 8Velocity Clinical Research at Medical City, Dallas, TX; 9Emory University School of Medicine, Atlanta, GA; 10Corcept Therapeutics Incorporated, Redwood City, CA
Background:
Excess cortisol activity (hypercortisolism) can contribute to hyperglycemia and may lead to poor control of type 2 diabetes (T2D), even with adherence to typically effective treatments. CATALYST (NCT05772169) was the largest prospective study to date to assess the prevalence of hypercortisolism in individuals with difficult-to-control T2D, finding a prevalence of 23.8% (n=252/1,057). With a participant cohort of >1,000, the study was uniquely positioned to explore demographic and clinical characteristics associated with difficult-to-control T2D.
Purpose:
Here we describe the characteristics of the CATALYST Part 1 population.
Methods:
Individuals aged 18-80 years with hemoglobin A1c (HbA1c) 7.5-11.5%, despite taking multiple antihyperglycemic medications, were screened for hypercortisolism using the 1-mg overnight dexamethasone suppression test (DST). Those with known causes of false-positive DSTs were excluded. The study was conducted in accordance with the ethics review committees, local regulations, and the International Council for Harmonisation’s Guideline for Good Clinical Practice.
Results:
The study population had a mean age of 60.7 years, 45% were female, 71% were White, 19% were African American, and 24% were Hispanic/Latino. Mean HbA1c was 8.8% and mean systolic blood pressure (SBP) was 127.6 mmHg. Overall, 31% had SBP ≥135 mmHg and 43% were taking ≥4 glucose-lowering medications, including sodium-glucose cotransporter 2 inhibitors (52%), glucagon-like peptide-1 receptor agonists (48%), and tirzepatide (10%). Antihypertensive medications were used by 82% of participants, with 27% taking ≥3 antihypertensives. Lipid-modifying medications (primarily statins) were used by 83%, psychiatric medications by 30%, and analgesic medications by 30% of participants. Cardiac disorders were present in 33% and 21% and hypertension was present in 89% and 79% of participants with and without hypercortisolism, respectively.
Conclusions:
CATALYST participants had a high medication and comorbid disease burden, with T2D that remained difficult to control despite multiple glucose-lowering medications. In addition, many participants had elevated SBP despite extensive use of antihypertensive medications.
Disclosures:
Richard Pratley reports consulting for Bayer, Corcept Therapeutics Incorporated, Gasherbrum Bio, Hanmi, Hengrui USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Sun Pharma, Sanofi, Scohia Pharma, Dexcom; grants from Hanmi, Metavention, Novo Nordisk, Poxel SA; speaker for Novo Nordisk.
Ralph A. DeFronzo reports: research support from AstraZeneca, Boehringer Ingelheim; speaker’s bureau with AstraZeneca; advisory board with AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics Incorporated, Intarcia, Novo Nordisk, Renalytix.
John Buse reports: grants or contracts from Bayer, Boehringer-Ingelheim, Carmot, Dexcom, Eli Lilly, Fractyl, Insulet, MannKind, Novo Nordisk, and vTv Therapeutics; institutional contracts with Novo Nordisk; consulting for Alkahest, Altimmune, American Diabetes Association, Anji, Aqua Medical Inc, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics Incorporated, Dasman Diabetes Institute (Kuwait City), Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Mediflix, Medscape, Medtronic MiniMed, Mellitus Health, Metsera, Moderna, Novo Nordisk, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Tandem, Terns Inc., and Vertex; honoraria from Boehringer-Ingelheim; expert testimony for Medtronic MiniMed and Novo Nordisk; stock ownership in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health; formerly on board of directors of the Association for Clinical and Translational Science.
Bradley Eilerman reports: speaker/consulting for AbbVie, Corcept Therapeutics Incorporated, Dexcom, Eli Lilly, and Novo Nordisk.
Vivian Fonseca reports: research support (to Tulane) with grants from Corcept Therapeutics Incorporated, Fractyl Health, Jaguar Gene Therapy; honoraria for consulting and lectures from Abbott, Asahi, Bayer, Boehringer Ingelheim, Corcept Therapeutics Incorporated; stock options in BRAVO4Health, Mellitus Health; stock in Abbott, Amgen; patents pending for 1) BRAVO risk engine for predicting diabetes complications and 2) PAX4 gene therapy for type 1 diabetes.
Yehuda Handelsman reports: research grant from Amgen, Applied Therapeutics, Corcept Therapeutics Incorporated, Ionis, Eli Lilly, Merck, Regeneron; advisory/consultant role with 89Bio, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics Incorporated, Esperion, MannKind, Merck, Pfizer, Novartis, Novo Nordisk, Sanofi, Regeneron; speaker’s bureau with Novo Nordisk.
John C. Parker reports: consultant/advisor: Corcept Therapeutics Incorporated, Novo Nordisk, and Insulet.
Julio Rosenstock reports: advisory panels with Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Hanmi, Intarcia, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals, Zealand Pharma; research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer, Sanofi.
Guillermo Umpierrez reports: research grants from the National Institutes of Health (NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program and the National Institutes of Health and National Center for Research Resources (NIH/National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] 2P30DK111024-06); research funding (to Emory University) for studies from Abbott, Bayer, Corcept Therapeutics Incorporated, Dexcom; member of advisory boards for Corcept Therapeutics Incorporated, Dexcom, GlyCare.
Daniel Einhorn reports: employed by and own stock in Corcept Therapeutics Incorporated.
11
The design of MOMENTUM: a prospective study of the prevalence of endogenous hypercortisolism in individuals with resistant hypertension
Jorge Plutzky,1 Jan N. Basile,2 Deepak L. Bhatt,3 Michael J. Bloch,4 Matthew A. Cavender,5 Yehuda Handelsman,6 Silvio E. Inzucchi,7 Neha J. Pagidipati,8 Raymond R. Townsend,9 Daniel Einhorn10
1Cardiovascular Medicine Division, Brigham and Women’s Hospital, Boston, MA; 2Division of Cardiology, Medical University of South Carolina, Charleston, SC; 3Mount Sinai Fuster Heart Hospital, New York, NY; 4Renown Institute for Heart and Vascular Health, Reno, NV; 5University of North Carolina at Chapel Hill, Chapel Hill, NC; 6Metabolic Institute of America, Tarzana, CA; 7Yale School of Medicine, New Haven, CT; 8Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; 9University of Pennsylvania School of Medicine, Philadelphia, PA; 10Corcept Therapeutics Incorporated, Redwood City, CA
Background:
Hypertension affects up to 50% of US adults and resistant hypertension (rHTN) occurs in 10-20% of cases. Endogenous hypercortisolism may contribute to rHTN in some individuals, but its prevalence in individuals with rHTN is currently unknown. The CATALYST study, which assessed the prevalence of endogenous hypercortisolism in individuals with difficult-to-control type 2 diabetes, reported a prevalence of 36.6% in participants with systolic blood pressure (BP) ≥135 mmHg despite taking ≥3 BP medications. The ongoing MOMENTUM study (ClinicalTrials.gov Identifier: NCT06829537) is the first large, prospective US study to examine the prevalence of endogenous hypercortisolism in individuals with rHTN.
Purpose:
The MOMENTUM study’s primary objective is to assess the prevalence of endogenous hypercortisolism in individuals with rHTN. Secondary objectives include evaluating associated clinical and laboratory characteristics in people with rHTN.
Methods:
MOMENTUM is an observational study of ~1,000 adults with rHTN defined using American Heart Association criteria. Key exclusion criteria are investigator-determined white coat hypertension, nonadherence to BP medications, and individuals in whom the dexamethasone suppression test is difficult to interpret. The primary endpoint is to assess the prevalence of endogenous hypercortisolism in this population. Key secondary endpoints are to assess clinical and laboratory features associated with increased risk of endogenous hypercortisolism. Hyperaldosteronism screening will also occur in the study. Descriptive statistics will be used to characterize participants with and without endogenous hypercortisolism. The study is being conducted in accordance with the ethics review committees, local regulations, and the International Council for Harmonisation’s Guideline for Good Clinical Practice.
Results:
The study is ongoing; final results are not yet available.
Conclusions:
The MOMENTUM study, as designed and currently enrolling, will provide an estimate of the prevalence of endogenous hypercortisolism and its associated clinical characteristics in people with rHTN.
Disclosures:
Jorge Plutzky reports: Consultant to Altimmune, Amgen, Boehringer Ingelheim, Corcept, New Amsterdam, Novo Nordisk, Toku Eyes; Clinical trial steering committee membership at Esperion, Novo Nordisk; research grant support from Boehringer Ingelheim, Novartis.
Jan N. Basile reports: Consultant to Eli Lilly, Novo Nordisk, Recor, Medtronic, Idorsia, Mineralys, Corcept; Research support from Recor, Ablative Solutions, Eli Lilly.
Deepak L. Bhatt reports: Consultant to Corcept.
Michael J. Bloch reports: Research support from Recor, Amgen, and SoniVie; Consultant/Honoraria for Recor, Medtronic, Amgen, Esperion, Janssen, Novartis, Idorsia, Barologics, and Corcept.
Matthew A. Cavender reports: Research support from Amgen, Boehringer Ingelheim, Cleerly, CSL Behring, Janssen, Novo Nordisk, Novartis, Silence Therapeutics, Massachusetts General Hospital/PCORI; Consulting for AbbVie, Bayer, Corcept, CSL Behring, Faraday Pharma, New Amsterdam Pharma, Novo Nordisk.
Yehuda Handelsman reports: Research grant from Amgen, Applied Therapeutic, Corcept, Ionis, Lilly, Merck, Regeneron; Advisory/Consultant role with 89Bio, Amgen, Applied Therapeutic, Arrowhead, AZ, Bayer, BI, Corcept, Esperion, Mankind Pharma, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Sanofi, and Regeneron; Speaker’s Bureau with Novo Nordisk.
Silvio E. Inzucchi reports: Consultant/advisor to Boehringer Ingelheim/Lilly, AstraZeneca, Novo Nordisk, Merck, Pfizer and Bayer.
Neha J. Pagidipati reports: Research support from Alnylam, Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, and Merck; Consultation/Advisory Panels for Amgen, Bayer, Boehringer Ingelheim, Corcept, Coursera, Eli Lilly, Esperion, AstraZeneca, Merck, New Amsterdam, Novartis, and Novo Nordisk; Medical advisory board for Miga Health.
Raymond R. Townsend reports: Consultant to Medtronic, Regeneron, AstraZeneca, BD, and Orchestra Backbeat; Data and Safety Monitoring Board at Axio/Cytel and Novartis; Royalty from UpToDate
Daniel Einhorn reports: employed by and own stock in Corcept Therapeutics.
12
Stage-Specific Impact of Chronic Kidney Disease on 30-Day Cardiac Outcomes After Endovascular Revascularization for Peripheral Artery Disease
Namra Khan, BS¹; Hana Shah, BS¹; Pura Rodriguez de la Vega, MPH²; Rupa Seetharamaiah, MD, FACS³˒⁴; Georgeta Vaidean, MD, MPH, PhD¹
¹ Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
² Department of Medical Education, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
³ Department of Surgery, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
⁴ Department of Surgery, Baptist Hospital of Miami, Miami, FL, USA
Background:
Chronic kidney disease (CKD) lies at the intersection of cardiovascular and metabolic disease, frequently overlapping with diabetes and hypertension. In patients with peripheral artery disease (PAD), CKD accelerates systemic vascular dysfunction and amplifies short-term cardiovascular vulnerability. While endovascular revascularization has become the predominant approach for PAD management, the stage-specific influence of CKD on perioperative outcomes remains poorly characterized. Understanding this relationship is critical for improving care within the cardio-renal-metabolic continuum.
Purpose:
This study evaluates the stage-specific impact of CKD on 30-day major adverse cardiac events (MACE) following lower extremity endovascular revascularization.
Methods:
We performed a retrospective cohort study of adults in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) registry from 2013-2022 who underwent lower extremity endovascular revascularization for PAD. Patients were stratified by preoperative estimated glomerular filtration rate (eGFR), calculated via the CKD-EPI 2021 equation, into five categories: G1 ≥90, G2 60-89, G3 30-59, G4 15-29, and G5 <15 mL/min/1.73m² or dialysis dependent. The primary outcome was 30-day MACE, defined as myocardial infarction, stroke, or death. Covariates included age, sex, race/ethnicity, admission type, American Society of Anesthesiologists (ASA) class, presenting symptoms (asymptomatic, claudication, rest pain, or tissue loss), preoperative hematocrit, and comorbidities including diabetes, hypertension, and congestive heart failure. Crude and adjusted associations between CKD severity and MACE, expressed as odds ratios (OR) with 95% confidence intervals (CI), were assessed using multivariable logistic regression.
Results:
The analytic cohort comprised 22,424 patients; 64.6% were ≥65 years, 36.1% were women, and 35.6% were non-White. Baseline characteristics demonstrated a clear gradient across CKD severity. Diabetes prevalence increased from about half of patients in G1 to more than 70% in G5. The prevalence of congestive heart failure, hypertension, and preoperative anemia also increased with worsening renal function, with anemia affecting the majority of patients in G5. Clinical severity and procedural complexity followed a similar pattern, as critical limb ischemia with tissue loss affected 38.5% of G1 patients compared with 74.9% in G5, while tibial-level interventions increased from 21.0% to 38.9% across the renal function spectrum. Within 30 days, 556 patients (2.5%) experienced a MACE. Event rates increased stepwise by CKD stage: 1.5% in G1, 1.6% in G2, 2.7% in G3, 4.9% in G4, and 6.0% in G5 (p<0.001). In the fully adjusted model, compared with G1, advanced stages were independent predictors for MACE, with OR (95% CI) 2.30 (1.50-3.52) for G4 and 3.15 (2.28-4.35) for G5. Patients in G2 and G3 showed no statistically significant excess risk after full adjustment.
Conclusions:
Advanced CKD conferred a two- to three-fold higher risk of perioperative MACE after endovascular PAD revascularization. This likely reflects the compounded effects of renal dysfunction, metabolic comorbidities, anemia, systemic inflammation, and vascular calcification. In contrast, mild-to-moderate CKD stages were not independently associated with MACE risk. These findings suggest the need for stage-specific perioperative assessment and integrated cardiometabolic management, including anemia correction, optimization of diabetes and hypertension, and tailored revascularization strategies. Future research should evaluate whether a nuanced incorporation of CKD staging into perioperative cardiac risk models enhances prediction, guides procedural selection, and improves outcomes for this vulnerable population.
Disclosures:
Nothing to disclose
13
The dual glucagon/GLP-1 receptor agonist survodutide improved cardiovascular risk biomarkers in adults with obesity in a phase 2 trial
Matthias Blüher1, Sandra González Maldonado2, Anita M. Hennige3, Elena Startseva4, Corinna Schoelch2
1Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI MAG) of the Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany
2Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
3Boehringer Ingelheim International GmbH, Biberach, Germany
4Boehringer Ingelheim International GmbH, Ingelheim, Germany
Background:
Survodutide is a unimolecular dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist in phase 3 clinical trials for chronic weight management in people living with obesity and, separately, for treating people with metabolic dysfunction-associated steatohepatitis. Survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks in a multinational phase 2 clinical trial in individuals with obesity without diabetes (NCT04667377).
Purpose:
To explore changes in molecular markers of adiposity, inflammation, insulin resistance, coagulation, and atherosclerosis.
Methods:
387 people aged ≥18 to <75 years with body mass index (BMI) ≥27 kg/m2 without diabetes were randomized to double-blind treatment for 46 weeks with once-weekly subcutaneous placebo or survodutide (doses escalated to 0.6, 2.4, 3.6 or 4.8 mg over up to 20 weeks with option to adjust dose for gastrointestinal tolerability, then maintained for the rest of the trial duration for each participant). In this pre-specified analysis, we evaluated plasma levels of multiple analytes, including leptin, intercellular adhesion molecule (ICAM)-1, E-selectin, apolipoprotein A, C-reactive protein (CRP), pigment epithelium-derived factor (PEDF), coagulation factor VII, and CC chemokine ligand 18 (CCL18) using a multiplex assay platform (Luminex xMAP). All participants receiving ≥1 dose of trial drug with data for ≥1 efficacy endpoint (the full analysis set [FAS]) were analyzed according to doses received during maintenance (actual treatment) using on-treatment data only and a mixed model for repeated measures.
Results:
Baseline demographic and clinical characteristics were similar between treatment groups in the FAS (n=384). Overall mean age was 49.1 years and BMI 37.1 kg/m2; 262 participants (68.2%) were female, 301 (78.4%) white, 40 (10.4%) Asian and 37 (9.6%) black. Compared to placebo, survodutide treatment was associated with significant decreases in plasma levels of leptin, ICAM-1 and E-selectin over time, as well as CRP, PEDF, coagulation factor VII, and CCL18. At week 46, adjusted fold changes for 4.8 mg survodutide versus placebo were 0.53 (95% confidence interval [CI], 0.43-0.66; p<0.0001) for leptin, 0.87 (0.81-0.94; p=0.0005) for ICAM-1, 0.74 (0.67-0.81; p<0.0001) for E-selectin, 0.60 (0.42-0.86; p=0.005) for CRP, 0.87 (0.81-0.93; p=0.0001) for PEDF, 0.83 (0.75-0.91; p=0.0001) for coagulation factor VII, and 0.87 (0.81-0.94; p=0.0005) for CCL18. Conversely, apolipoprotein A levels were increased in participants receiving survodutide compared with those receiving placebo over time; the adjusted fold change at week 46 for 4.8 mg versus placebo was 1.30 (95% CI, 1.12-1.51; p=0.0007).
Conclusions:
In this pre-specified exploratory analysis of a phase 2 trial, treatment with the dual GCGR/GLP-1R agonist survodutide was associated with improvements in molecular markers of cardiometabolic health and cardiovascular risk in people living with obesity.
Disclosures:
Blüher has received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer and Sanofi; and has participated on a data safety monitoring board/advisory board for Boehringer Ingelheim. S. González Maldonado, A. M. Hennige, E. Startseva and C. Schoelch are employees of Boehringer Ingelheim.
The study was supported and funded by Boehringer Ingelheim (BI). Survodutide is licensed to BI from Zealand Pharma, with BI solely responsible for development and commercialization globally; Zealand has a co-promotion right in the Nordic countries. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the abstract. Giles Brooke, PhD, CMPP, of Envision Ignite, an Envision Medical Communications agency, a part of Envision Pharma Group provided writing support, which was contracted and funded by BI. BI was given the opportunity to review the abstract for medical and scientific accuracy as well as intellectual property considerations.
14
Factors Influencing the Progression of Target and Non-target Coronary Lesions with a Focus on High Glucose
Shiqi Liu, Dong Wang, Chengchun Tang
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University
Background:
With improvements in lifestyle and shifts in dietary habits, the prevalence of aging- and metabolism-related diseases has increased, making coronary heart disease a major public health concern. With the exploration of the mechanism of atherosclerosis and the development of clinical drug, stent and balloon technologies, the treatment of coronary heart disease has risen to the level of how to prevent in-stent restenosis and the rapid progression of non-target lesions. Identifying potential risk factors for in-stent restenosis and the progression of non-target lesions through large-scale data analysis provides valuable guiding for clinical practice. Blood glucose plays a significant role in the progression of atherosclerosis. Evidence indicates that patients with hyperglycemia experience a higher incidence of coronary heart disease and worse clinical outcomes. In this study, we focus on the indicators of abnormal blood glucose fluctuations to explore their impact on the prognosis of coronary artery disease.
Purpose:
The purpose of this study is to investigate the association between stress hyperglycemia ratio (SHR) and adverse coronary outcomes, specifically the progression of non-target lesions (NTLs) and the development of in-stent restenosis (ISR) in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). While drug-eluting stents and drug-coated balloons have markedly reduced the incidence of ISR over the past decade, the progression of NTLs has emerged as an important cause of recurrent ischemic events and remains a major challenge in long-term management after PCI. Abnormal glycemic states, including glucose fluctuations and intermittent hyperglycemia, have been increasingly recognized as contributors to systemic inflammation, oxidative stress, and vascular dysfunction, which may accelerate atherosclerotic progression. This study aims to clarify the predictive value of SHR for ISR and NTL progression, and to further elucidate the underlying pathophysiological mechanisms.
Methods:
This study retrospectively enrolled patients with acute coronary syndrome who underwent stent implantation and follow-up coronary angiography at Zhongda Hospital between January 2020 and January 2025. Patients were followed for up to 24 months, and the incidence of in-stent restenosis (ISR) and progression of non-target lesions (NTLs) was assessed. Baseline clinical characteristics and laboratory data were collected. Stress-induced hyperglycemia ratio (SHR) was calculated using the formula: ABG (mmol/L) ÷ (1.59 × HbA1c [%] – 2.59). Logistic regression model, restricted cubic spline analysis (RCS), and machine learning algorithms (LightGBM, decision tree, and XGBoost) were used to analyze the relationship between SHR and ISR and NTLs progression.
For experimental validation, a carotid guidewire injury model was established in ApoE⁻/⁻ mice to assess vascular injury progression in target and non-target lesions under abnormal glycemic conditions. Intermittent hyperglycemia, simulating postprandial fluctuations in non-diabetic individuals, was induced by intraperitoneal glucose injection every 2 hours during daytime, 2-3 times per week, and maintained for 12 weeks. Atherosclerotic changes in both carotid arteries were then examined. In vitro, vascular endothelial cells were exposed to similar intermittent high glucose stimulation, and proliferation, apoptosis, inflammatory cytokine release, and oxidative stress were assessed.
Results:
A total of 1,644 patients with acute coronary syndrome (ACS) were enrolled. During follow-up, 12.7% experienced in-stent restenosis (ISR) and 24.3% developed non-target lesions (NTLs) progression. Logistic regression analysis identified stress-induced hyperglycemia ratio(SHR), left ventricular ejection fraction (LVEF), and the number of implanted stents were identified as risk factors for ISR, SHR, blood pressure, high-density lipoproteincholesterol (HDL-c) , as well as the number and severity of NTLs as risk factors for NTLs progression. After multivariable adjustment, SHR remained independently associated with both ISR and NTLs progression (OR = 2.33, 95% CI: 1.26-4.31, p = 0.007, OR = 2.04, 95% CI: 1.12-4.02, p = 0.007). Restricted cubic spline (RCS) analysis demonstrated a near-linear association between SHR and both outcomes, with risks significantly increasing when SHR exceeded 0.96 (P=0.026, P=0.0047, respectively).
Among machine learning models, the AUC of the XGboost prediction model for ISR was 0.70 (95% CI: 0.67, 0.78). Higher SHR, more stents, higher age, and poorer cardiac function predicted the occurrence of ISR. The hybrid model combining logistic regression and XGBoost had the best predictive effect of NTLs progression, with an AUC of 0.78 (95% CI: 0.71, 0.86), taking into account SHR, the number of non-target lesions (NTLs), the degree of stenosis, hypertension and high-density lipoprotein cholesterol (HDL-c). Subgroup analysis showed that compared with diabetic patients, elevated SHR in non-diabetic patients was a stronger predictor.
In the animal experiments, ApoE⁻/⁻ mice subjected to carotid guidewire injury exhibited endothelial damage. After a 12-week high-fat diet with intermittent hyperglycemia, injured carotid artery (target lesion) developed severe plaque, while the contralateral uninjured carotid artery (non-target lesions) was more severe than that in mice without intermittent hyperglycemia or diabetic mice. Histological staining confirmed more severe plaque burden (HE), lipid deposition (Oil Red O), and macrophage infiltration (CD68⁺). In vitro, endothelial cell exposed to intermittent high glucose exhibited markedly reduced cell viability, increased apoptosis and elevated secretion of IL-6, IL-1β and TNF-α, along with higher intracellular ROS levels.
Conclusions:
Five-year data indicate that the incidence of ISR has markedly declined since the introduction of drug-coated balloons, falling below 10% in the past two years. However, the progression of NTLs remains consistently high and has become a major source of potential risk and adverse events after PCI in patients with acute coronary syndrome. This study demonstrated that abnormal glucose fluctuations in non-diabetic patients trigger a more pronounced systemic inflammatory and oxidative stress response than sustained hyperglycemia, thereby accelerating the progression of both target and non-target lesions. Compared with in-stent restenosis, the risk of NTLs progression is not only related to the number and severity of NTLs, but also strongly linked to systemic conditions such as dysglycemia, dyslipidemia, and hypertension. Poor control of these risk factors aggravates systemic inflammation and oxidative stress, further promoting atherosclerosis. These findings provide new insights into the long-term management of ACS following PCI and highlight the importance of strict control of glucose to reduce future adverse cardiovascular events.
Disclosures:
Nothing to disclose by any authors.
15
Eicosapentaenoic acid ethyl ester mitigates triglyceride-induced liver-adipose axis dysregulation and enhances insulin sensitivity
Zeeba Saeed1, Sebastià Alcover2, Lisaidy Ramos-Regalado2, Sergi Otero2, Gabriela O Girón2, Sergi López2, Giulia Renda1,3, Gemma Vilahur2
1 Center for Advanced Studies and Technology, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
2 Research Institut Sant Pau (IR SANT PAU), Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
3Department of Neuroscience, Imaging and Clinical Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
Background:
Hypertriglyceridemia (HTG) is associated with elevated risk of cardiovascular events. Clinical studies have demonstrated that eicosapentaenoic acid ethyl ester (EPA-E) treatment significantly reduces triglyceride levels and improves cardiovascular outcomes. However, the mechanisms underlying these beneficial effects are not yet fully understood.
Purpose:
This study investigates the potential of EPA-E treatment to mitigate triglyceride (TG)-induced metabolic dysregulation, focusing on the liver-adipose tissue cross-talk.
Methods:
Male Wistar-Hannover rats (n=42) were fed a high-sucrose diet for 6 weeks. HTG was confirmed at week 4 (TG levels ≥175mg·dL-1) and, thereafter, HTG rats were divided into two groups; 1) EPA-E treated group (HTG+EPA, n=15), receiving a high dose of EPA-E (0.3g·kg-1) for 2 weeks, and 2) an untreated group (HTG, n=14). A control diet group (CD, n=13) was also run for comparative purposes. We determined serum lipid profiles, lipoprotein particle distribution, glycoprotein inflammatory biomarkers and liver and subcutaneous adipose tissue lipid contents using proton-nuclear magnetic resonance (¹H-NMR). Liver protein expression of Akt and phosphorylated (activated) Akt were also evaluated.
Results:
Insulin resistance was confirmed at 4 weeks by an increased triglyceride-glucose (TyG) index in both HTG and HTG+EPA. Interestingly, EPA-E treatment reduced the TyG index after just 2 weeks. This improvement was accompanied by increased Akt activation in the liver of EPA-E treated rats, supporting enhanced insulin signalling pathway.
As per lipid profile, EPA-E treatment ameliorated the HTG-derived atherogenic dyslipidemic profile, evidenced by a significant decline in VLDL-TG, HDL-TG and larger diameters of VLDL and LDL particles. Serum levels of inflammatory biomarkers, including glycoprotein A (a marker associated with high cardiovascular risk) and glycoprotein F, were significantly reduced in the EPA-E treated group compared to the HTG rats. Furthermore, an inverse correlation was observed between glycoprotein A levels and atherogenic profile. Liver lipidomic analyses revealed a significant increase in omega-3 fatty acids, particularly EPA, in EPA-E treated animals. No differences were detected as per omega-3 content in the subcutaneous adipose tissue across groups. However, EPA-E treatment reduced TG levels in both liver and adipose tissue as compared to the non-treated group. High TG and saturated fatty acids in the adipose tissue of HTG rats seemingly contributed to an increase in serum levels of non-esterified fatty acids and liver TG accumulation. EPA-E mitigated this dysregulation, indicating a beneficial effect on the liver-adipose tissue connection.
Conclusions:
Our findings provide evidence that EPA-E treatment exerts metabolic beneficial effects within the liver-adipose tissue axis by reducing atherogenic dyslipidemia, TG accumulation, and low-grade inflammation while improving insulin sensitivity. These data support the metabolic benefits of EPA-E beyond its hypotriglyceridemic properties.
Disclosures:
Nothing to disclose by any authors.
16
Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk
Stephen J Nicholls MBBS PhD1, Adam J Nelson MBBS PhD1, Marc Ditmarsch MD2, John JP Kastelein MD PhD2,3, Christie M Ballantyne MD4, Kausik K Ray MD MPhil FMedSci5, Ann Marie Navar MD6, Steven E Nissen MD7, Mariko Harada(NCT05142722)-Shiba MD8, Andrew Hsieh PharmD2, for the BROADWAY investigators*
From the 1Victorian Heart Institute, Monash University, Clayton, Australia; 2NewAmsterdam Pharma, Amsterdam, Netherlands; 3Department of Vascular Medicine, University of Amsterdam, Amsterdam, Netherlands; 4Baylor College of Medicine and the Texas Heart Institute, Houston, TX; 5Imperial College London, London, UK; 6UT Southwestern Medical Center, Dallas, TX; 7Cleveland Clinic, Cleveland, OH; 8Cardiovascular Center, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Background:
Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that lowers low-density lipoprotein (LDL) cholesterol levels.
Purpose:
The efficacy and safety of obicetrapib have not been fully characterized in patients at high risk of cardiovascular events.
Methods:
BROADWAY (NCT05142722) enrolled 2530 patients with familial hypercholesterolemia (FH) or a history of atherosclerotic cardiovascular disease (ASCVD), treated with maximally tolerated lipid lowering therapy. Patients with either LDL cholesterol ³100 mg/deciliter and/or non-high-density lipoprotein (non-HDL) cholesterol ³130 mg/deciliter or LDL cholesterol 55-100 mg/deciliter and/or non-HDL cholesterol 85-130 mg/deciliter with at least one additional cardiovascular risk factor were randomized (2:1) to obicetrapib 10 mg or matching placebo daily for 365 days. The primary endpoint was the percent change from baseline to Day 84 in LDL cholesterol.
Results:
Patients (mean age 65 years, female 33%, White race 74%, ASCVD 89%, FH 16%, statin use 90%) had a mean baseline LDL cholesterol level of 98 mg/deciliter. The difference between placebo and obicetrapib for the change in LDL cholesterol was -32.7% (95% confidence interval [CI] -35.8, -29.5), P<0.0001. The percent change from baseline in LDL cholesterol at day 84 was +2.7% (95% CI -0.4, 5.8) with placebo and -29.9% (95% CI -32.1, -27.8) with obicetrapib. The incidence of adverse events was similar across treatment groups.
Conclusions:
Obicetrapib was well tolerated and produced placebo-adjusted LDL cholesterol reductions of 32.7% in patients at high risk of cardiovascular events with elevated lipid levels despite treatment with maximally tolerated lipid-lowering therapy.
Disclosures:
SJN received grant/research support from AstraZeneca, NewAmsterdam Pharma, Amgen,Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo,Silence Therapeutics, CSL Seqirus and Vaxxinity.
AJN has received research support from Astra Zeneca, Amgen, Eli Lilly, Novartis and is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, CSL Sequiris, Eli Lilly, GSK, Novartis, Novo Nordisk, Sanofi Pasteur, Vaxxinity.
CMB has received grant or research support from Abbott Diagnostic, Akcea, Amgen,Arrowhead, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Roche Diagnostics, NIH, AHA and ADA and is a consultant for 89Bio, Abbott Diagnostics, Amarin, Amgen,Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Illumina, Ionis, Eli Lilly, Merck,NewAmsterdam Pharma, Novartis, Novo Nordisk and Roche Diagnostic.
KKR reports Research grants- Amgen, Sanofi, Regeneron, Daiichi Sankyo, and Ultragenyx to Imperial College London.
Consultancy-Novartis, Daiichi Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, SilenceTherapeutics, AZ, NewAmsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio,Scribe, Crispr, Vaxxinity, Amarin, Regeneron, Ultragenyx, Sanofi Cargene, and Resverlogix.Fees for lectures-Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi,Amgen, Esperion, Daiichi Sankyo, Mankind, Macleod Pharma for symposia at international meetings. Holding stock options from NewAmsterdam Pharma, SCRIBE therapeutics andPemi31.
AMN has received research support to her institution from Amgen and Esperion and personal fees for consulting from Amgen, Arrowhead, Astra Zeneca, Bayer, Eli Lilly, Esperion,Janssen, Merck, NewAmsterdam, Novartis, Novo Nordisk, Pfizer, Roche, and Silence Therapeutics. SEN has received research funding to perform clinical trials from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Esperion Therapeutics, Medtronic, MyoKardia, NewAmsterdam Pharma, Novartis, Pfizer, and Silence Therapeutics.
MHS has received fees for consulting or lectures from Amgen, Boehringer, MEDPACE Japan, BML, Protosera, Novartis, Ultragenyx, Recordati Rare Disease, Kaneka Medics, Kowa and Alexion, stock from Liid Pharma.
BAF has received research grants and consulting fees from Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, dalCOR, Eli Lilly, Esperion, Ionis Pharmaceuticals, KrKa Pharmaceuticals, Merck, Mylan, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, The Medicines Company and Viatris.
UL has received fees for consulting or lectures from Amgen, Boehringer, Daiichi Sankyo, NewAmsterdam Pharma, Novartis, Sanofi. Leipzig University received research funding from Amgen, Daiichi Sankyo, Novartis, Sanofi.
MB has received grant(s)/research support from Amgen, Daiichi-Sankyo, Mylan/Viatris, Sanofi and Valeant, and has served as a consultant and/or received speaker’s fees from Adamed, Amgen, Exceed Pharma, Daiichi-Sankyo, Esperion, Kogen, KRKA, Lilly, MSD, Mylan/Viatris, NewAmsterdam Pharma, Novartis, Novo-Nordisk, Polpharma, Sanofi, Teva and Zentiva.
RM reports institutional research payments from Abbott, Alleviant Medical, Beth Israel Deaconess Medical Center, Concept Medical, Cordis, Elixir Medical, Faraday Pharmaceuticals, Idorsia Pharmaceuticals, Janssen, MedAlliance, Mediasphere Medical, Medtronic, Novartis, Protembis GmbH, RM Global Bioaccess Fund Management, Sanofi US Services, Inc and has received personal fees from Elixir Medical, IQVIA, Medtronic, Medscape/WebMD Global and Novo Nordisk and has equity in Elixir Medical, Stel and ControlRad (spouse).
ALC has received honoraria, lecture fees or research grants from Amarin, Amgen, AstraZeneca, Chiesi, Daiichi Sankyo, Eli Lilly, Esperion, Ionis Pharmaceutical, Medscape, Menarini, MSD, Novartis, Novo Nordisk, Regeneron, Sanofi, Ultragenyx and Viatris. MS serves as a consultant for and/or has received research support from Lexicon, Amarin, NewAmsterdam Pharma, Silence, Sanofi, Regeneron, and Tourmaline. MS also receives salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2024 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA biopharma, Inc., Arrowhead Pharmaceuticals, AstraZeneca Pharma India, AstraZeneca UK Ltd, Bayer, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, Cleerly, Inc., Colorado Dept of Public Health and Environment, Congress Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd., Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc., HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc, Janssen Research & Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc., Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Nectero Medical, Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham and Women’s Hospital, Thrombosis Research Institute, Tourmaline Bio, Inc, University of Colorado, University of Colorado Denver, University of Pittsburgh, VarmX, Verve Therapeutics, WraSer, LLC.
VB is an employee of MedPace.
MD, JJPK, DLC, AN, DK, AH and MHD are employees of NewAmsterdam Pharma and hold stocks or options.
JB and YH have no potential conflicts to disclose.
17
Impact Of Obicetrapib On Major Adverse Cardiovascular Events: A Pooled Analysis Of Phase 3 Clinical Trials
Stephen J Nicholls MBBS PhD1, Adam J Nelson MBBS PhD1, Kausik K Ray MD MPhil FMedSci3,Marc Ditmarsch MD4, Douglas Kling MBA4, Andrew Hsieh, PharmD4, Michael Szarek, PhD5, John JP Kastelein, MD, PhD4, Michael H.Davidson, MD4
From the 1Victorian Heart Institute, Monash University, Clayton, Australia; 2Imperial College London, London, UK; 3NewAmsterdam Pharma, Amsterdam, Netherlands; 4State University of New York Downstate School of Public Health, Brooklyn, NY
Background:
The highly selective cholesteryl ester transfer protein inhibitor, obicetrapib, decreases levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] and raises high-density lipoprotein cholesterol (HDL-C) in patients treated with maximally tolerated statin therapy as evident within the Phase III BROOKLYN (NCT05425745) trial assessing the effects of daily administration of obicetrapib 10 mg compared with matching placebo (2:1) for 365 days on changes in lipid and lipoprotein parameters in 364 patients with heterozygous familial hypercholesterolemia (HeFH)) and in the Phase III BROADWAY (NCT05142722) trial involving 2530 patients with atherosclerotic cardiovascular disease (ASCVD) with or without HeFH.
Purpose:
Since the effect of obicetrapib on cardiovascular events is unknown, a pooled analysis of both BROOKLYN and BROADWAY trials was conducted.
Methods:
The time to first occurrence of major adverse cardiovascular events was compared between the treatment groups in a pooled analysis of both trials in an analysis that included stratification by the presence of HeFH, statin intensity at baseline and study.
Results:
The pooled cohort had a median age of 66 years, 36% were female with a history of ASCVD in 82%, HeFH in 27% and diabetes in 35%. Baseline medication use included statins in 91%, high-intensity statins in 69%, ezetimibe in 30% and PCSK9 inhibitors in 5%. Median baseline lipid levels included LDL-C of 92 mg/dL, HDL-C of 48 mg/dL, apoB of 87 mg/dL and Lp(a) of 40.5 nmol/L. Treatment with obicetrapib produced greater reductions in LDL-C (-37.8% vs -4.6%), apoB (-21.7% vs -3.6%) and Lp(a) (-32.5% vs 0%) and greater increases in HDL-C (+140.0% vs +1.5%) compared with placebo. The incidence of the composite of coronary heart disease death, myocardial infarction, ischemic stroke or coronary revascularization was lower in the obicetrapib group (3.9% vs 5.0%, HR (95% CI) 0.77 (0.54, 1.11), P=0.16). A time-based analysis revealed no effect of obicetrapib in the first 6 months (HR (95% CI) 1.03 (0.59, 1.78), P=0.92) and a reduction in risk in the second 6 months (HR (95% CI) 0.60 (0.37, 0.99), P=0.04). The incidence of the composite of coronary heart disease death, myocardial infarction or coronary revascularization was lower in the obicetrapib group (3.2% vs 4.7%, HR (95% CI) 0.68 (0.46, 1.00), P=0.048). A time-based analysis revealed no effect of obicetrapib in the first 6 months (HR (95% CI) 1.06 (0.60, 1.90), P=0.83) and a reduction in risk in the second 6 months (HR (95% CI) 0.45 (0.26, 0.77), P=0.003). Mediation analysis will investigate whether changes in LDL-C, apoB, Lp(a) and HDL-C contribute to the reduction in cardiovascular events.
Conclusions:
Treatment of high cardiovascular risk patients with obicetrapib resulted in a decrease in LDL-C, apoB and Lp(a), increase in HDL-C and a reduction in coronary events, which became evident beyond 6 months of treatment. This highlights the potential for obicetrapib to be a useful adjunctive therapy to lower cardiovascular risk.
Disclosures:
SJN received grant/research support from AstraZeneca, NewAmsterdam Pharma, Amgen,Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company,Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant forAbcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo,Silence Therapeutics, CSL Seqirus and Vaxxinity.
AJN has received research support from AstraZeneca, Amgen, Eli Lilly, Novartis and is a consultant for Amgen, AstraZeneca,Boehringer Ingelheim, CSL Sequiris, Eli Lilly, GSK, Novartis, Novo Nordisk, Sanofi Pasteur,Vaxxinity. CMB has received grant or research support from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Roche Diagnostic,NIH, AHA and ADA and is a consultant for 89Bio, Abbott Diagnostics, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Illumina, Ionis, Eli Lilly, Merck,NewAmsterdam Pharma, Novartis, Novo Nordisk and Roche Diagnostics.
KKR reports Research grants- Amgen, Sanofi, Regeneron, Daiichi Sankyo, and Ultragenyx to Imperial College London.
Consultancy-Novartis, Daiichi Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, Silence Therapeutics, AZ, NewAmsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio,Scribe, Crispr, Vaxxinity, Amarin, Regeneron, Ultragenyx, Sanofi Cargene, and Resverlogix. Fees for lectures-Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi,Amgen, Esperion, Daiichi Sankyo, Mankind, Macleod Pharma for symposia at international meetings. Holding stock options from NewAmsterdam Pharma, SCRIBE therapeutics and Pemi3
MS reports consultancy fees for and/or has received research support from Lexicon, Amarin, NewAmsterdam, Silence, Sanofi, Regeneron, and Tourmaline. MS also receives salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2024 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA biopharma, Inc., Arrowhead Pharmaceuticals, AstraZeneca Pharma India, AstraZeneca UK Ltd, Bayer, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, Cleerly, Inc., Colorado Dept of Public Health and Environment, Congress Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd., Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc., HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc, Janssen Research & Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc., Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Nectero Medical, Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham and Women’s Hospital, Thrombosis Research Institute, Tourmaline Bio, Inc, University of Colorado, University of Colorado Denver, University of Pittsburgh, VarmX, Verve Therapeutics, WraSer, LLC.
MD, DK, AH, JJPK and MHD are employees of NewAmsterdam Pharma and hold stocks or options.
Acknowledgements:
These data have been previously presented as a Late Breaker oral presentation at the European Society of Cardiology (ESC) 2025 Scientific Sessions, on Monday, September 1, 2025.
Obicetrapib is an experimental/investigational CETP inhibitor that is intended to treat dyslipidemia and is currently not regulatory approved.
18
Effect of Obicetrapib on New Onset Diabetes In Patients with Elevated LDL-C Receiving Maximally Tolerated Statin Therapy: Pooled Analyses of the Broadway and Brooklyn Trials
Kausik K. Ray1, Michael Szarek2, Ann Marie Navar3, Adam J. Nelson6, Christie M. Ballantyne4, Douglas Kling5, Marc Ditmarsch5, Michael H. Davidson5, John J.P. Kastelein5, Stephen J. Nicholls6
From the 1Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, UK;
2State University of New York, Downstate School of Public Health, Brooklyn, NY;
3UT Southwestern, Dallas, TX; 4Baylor College of Medicine, Houston, TX; 5NewAmsterdam Pharma, Amsterdam, Netherlands; 6Victorian Heart Institute, Monash University, Clayton, Australia
Background:
Clinical trials and genetic studies indicate that the cardiovascular benefits of low-density lipoprotein cholesterol (LDL-C) lowering are proportional to their degree of LDL-C lowering, not the mechanism by which it is achieved. By contrast, the effects of LDL-C lowering on glycemic control and new onset diabetes (NoD) vary by intervention. Although genetics predict an on-target effect on HMGCoA, NCP1L1 and PCSK9 lowering on risk of NoD, this has only been observed in trials of statins (HMGCoA inhibition). Obicetrapib is a cholesteryl ester transfer protein inhibitor (CETPi) that reduces LDL-C and Lp(a) and raises apoA1/HDL-C. Meta-analyses of early CETPi trials demonstrated a 16% lower risk of NoD.
Purpose:
Given that the effects of Obicetrapib on glycaemia and risk of NoD are unknown, we have conducted a pooled analysis of obicetrapib’s Phase III trials.
Methods:
Pooled analysis of patients in the Phase III BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) trials which randomized patients with ASCVD or HeFH with elevated LDL-C despite maximally tolerated statins to Obicetrapib 10mg once daily or placebo for 1 year. The effect of Obicetrapib on HbA1c at days 84 and 365 and risk of NoD was assessed in patients without a known history of diabetes at baseline and by glycemia strata (prediabetes, or normoglycemia) using standard criteria with adjustment for baseline HbA1c, trial and statin use at baseline. We also conducted an updated meta-analysis of the risk of NoD with CETPi including Obicetrapib data assess whether any observed associations were consistent with prior class-level observations.
Results:
A total of 1848 patients were included; mean age 63.4, women 38.1%, 89.7% on statin. Baseline median LDL-C was 96 mg/dl (IQR 78-126), HbA1c was 5.7% (5.4%-5.9%). Placebo corrected median changes in LDL-C, Lp(a) and HDL-C were -35.3%, -35.6%, and +136.7%, respectively, all P <0.0001. Post-baseline HbA1c was lower with Obicetrapib vs Placebo, p <0.0297), with consistent by glycemia stratum . The treatment HR for NoD was 0.77 (95% CI 0.57-1.04), p=0.09 with consistent trends in those within normoglycemia and prediabetes. In an updated meta-analysis, including obicetrapib data with that from 4 prior large RCTS produced an overall RR for NoD of 0.83 (CI 0.77-0.90), I2 13.5%, p-value for heterogeneity 0.493, consistent with an overall class effect for CETPi.
Conclusions:
Obicetrapib reduced HbA1c with a trend towards a lower risk of NoD in those with prediabetes and normoglycemia at baseline. Although obicetrapib led to greater LDL-C reductions than other CETPi, the effects of Obiceterapib on NoD were consistent with other CETPi. As risk of NoD accrues over time, larger and longer trials are needed to determine the full degree of potential protective effects of Obicetrapib on risk of NoD.
Disclosures:
KKR reports Research Grants- Amgen, Sanofi, Regeneron, Daiichi Sankyo, and Ultragenyx to Imperial College London.
Consultancy-Novartis, Daiichi Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, SilenceTherapeutics, AZ, NewAmsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio,Scribe, Crispr, Vaxxinity, Amarin, Regeneron, Ultragenyx, Sanofi Cargene, and Resverlogix.Fees for lectures-Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi,Amgen, Esperion, Daiichi Sankyo, Mankind, Macleod Pharma for symposia at international meetings. Holding stock options from NewAmsterdam Pharma, SCRIBE therapeutics andPemi31.
MS serves as a consultant for and/or has received research support from Lexicon, Amarin, NewAmsterdam Pharma, Silence, Sanofi, Regeneron, and Tourmaline. MS also receives salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2024 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA biopharma, Inc., Arrowhead Pharmaceuticals, AstraZeneca Pharma India, AstraZeneca UK Ltd, Bayer, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, Cleerly, Inc., Colorado Dept of Public Health and Environment, Congress Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd., Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc., HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc, Janssen Research & Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc., Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Nectero Medical, Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham and Women’s Hospital, Thrombosis Research Institute, Tourmaline Bio, Inc, University of Colorado, University of Colorado Denver, University of Pittsburgh, VarmX, Verve Therapeutics, WraSer, LLC.
AMN has received research support to her institution from Amgen and Esperion and personal fees for consulting from Amgen, Arrowhead, Astra Zeneca, Bayer, Eli Lilly, Esperion, Janssen, Merck, NewAmsterdam, Novartis, Novo Nordisk, Pfizer, Roche, and Silence Therapeutics. SEN has received research funding to perform clinical trials from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Esperion Therapeutics, Medtronic, MyoKardia, NewAmsterdam Pharma, Novartis, Pfizer, and Silence Therapeutics.
AJN has received research support from Astra Zeneca, Amgen, Eli Lilly, Novartis and is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, CSL Sequiris, Eli Lilly, GSK, Novartis, Novo Nordisk, Sanofi Pasteur, Vaxxinity.
CMB has received grant or research support from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Roche Diagnostics, NIH, AHA and ADA and is a consultant for 89Bio, Abbott Diagnostics, Amarin, Amgen,Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Illumina, Ionis, Eli Lilly, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk and Roche Diagnostic
DK, MD, MHD, JJPK are employees of NewAmsterdam Pharma and hold stocks or options.
SJN received grant/research support from AstraZeneca, NewAmsterdam Pharma, Amgen, Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo,Silence Therapeutics, CSL Seqirus and Vaxxinity. AJN has received research support from AstraZeneca, Amgen, Eli Lilly, Novartis and is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, CSL Sequiris, Eli Lilly, GSK, Novartis, Novo Nordisk, Sanofi Pasteur, Vaxxinity. CMB has received grant or research support from Abbott Diagnostic, Akcea, Amgen,Arrowhead, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Roche Diagnostics, NIH, AHA and ADA and is a consultant for 89Bio, Abbott Diagnostics, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Illumina, Ionis, Eli Lilly, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk and Roche Diagnostic.
Acknowledgements
These data have been previously presented at the National Lipid Association (NLA) 2025 Scientific Sessions, in Miami, Florida.
Obicetrapib is an experimental/investigational CETP inhibitor that is intended to treat dyslipidemia and is currently not regulatory approved.
These data have been previously presented at the National Lipid Association (NLA) 2025 Scientific Sessions, in Miami, Florida.
19
Impact of Cholesteryl Ester Transfer Protein Inhibitor, Obicetrapib, on Lipoprotein(a) Levels: Pooled Data from Phase 3 Clinical Trials
Stephen J Nicholls MBBS PhD1, Kausik K Ray MD MPhil FMedSci2, Michael Szarek, PhD3, Marc Ditmarsch, MD4, Douglas Kling, MBA4, Andrew Hsieh PharmD4, Adam J Nelson MBBS PhD1, Michael H. Davidson, MD4 and John JP Kastelein, MD, PhD4
From the 1Victorian Heart Institute, Monash University, Clayton, Australia; 2Imperial College London, London, UK; 3Mt Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY; 4NewAmsterdam Pharma, Amsterdam, Netherlands
Background:
Increasing evidence implicates lipoprotein(a) [Lp(a)] in the causality of atherosclerotic cardiovascular disease (ASCVD). This has stimulated efforts to develop therapies that lower Lp(a) levels. While all patients with ASCVD require low-density lipoprotein cholesterol (LDL-C) lowering, 50% have Lp(a) levels greater than 50 nmol/L that are likely to promote residual risk. Therapies that lower both LDL-C and Lp(a) in this setting have the potential to produce cardiovascular benefit, since they are both independent risk factors. The highly selective cholesteryl ester transfer protein (CETP) inhibitor, obicetrapib, reduced LDL-C by up to 51% and raised high-density lipoprotein cholesterol (HDL-C) up to 165% in early trials.
Purpose:
Given that the impact of obicetrapib on Lp(a) levels remains to be fully elucidated, a pooled analysis of obicetrapib’s Phase III studies was conducted to investigate the impact of obicetrapib on changes in Lp(a) levels in patients with baseline levels greater than 50 nmol/L.
Methods:
A pooled analysis was performed of Phase III clinical trials evaluating the impact of obicetrapib on lipid levels including (1) BROADWAY (NCT05142722) evaluating obicetrapib and placebo in patients with heterozygous familial hypercholesterolemia (HeFH) or ASCVD, (2) BROOKLYN (NCT05425745) evaluating obicetrapib and placebo in patients with HeFH and (3) TANDEM (NCT06005597) evaluating the fixed dose combination of obicetrapib, ezetimibe, obicetrapib/ezetimibe and placebo in patients with or at high risk of ASCVD. Median differences in placebo-adjusted percentage and absolute changes in LDL-C and Lp(a) from baseline to day 84 were determined by Hodges-Lehman analyses.
Results:
Patients (n=2538) had median baseline levels of LDL-C of 92 mg/dL and Lp(a) of 42.7nmol/L. Obicetrapib produced placebo-adjusted reductions in LDL-C by 37.4% and 35.0 mg/dL. The correlation between absolute changes in apoB and LDL-C was r=0.88, however the correlation between absolute change in apoB and Lp(a) was r=0.18. In patients with baseline Lp(a) levels > 50 but below 150 nmol/L, obicetrapib produced placebo-adjusted percent reductions in Lp(a) by 44.8% and absolute reductions in Lp(a) by 37.4 nmol/L. While patients with baseline Lp(a) > 150 nmol/L demonstrated a lower percentage reduction in Lp(a) with obicetrapib than those with baseline levels between 50 and 150 nmol/L, the absolute reduction in Lp(a) was similar in both groups (-33.1 vs. -37.4 nmol/L).
Conclusions:
Obicetrapib administration results in reductions in levels of both LDL-C and Lp(a). The absolute reduction in Lp(a) was similar in patients with mildly elevated Lp(a) levels, who are unlikely to qualify for administration of RNA targeted Lp(a) lowering agents. These combined effects of obicetrapib on both LDL-C and Lp(a) have the potential to be an effective approach to lowering cardiovascular risk. This is undergoing evaluation in a large cardiovascular outcomes trial.
Disclosures:
SJN received grant/research support from AstraZeneca, NewAmsterdam Pharma, Amgen, Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and was a consultant for Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo,Silence Therapeutics, CSL Seqirus and Vaxxinity. AJN has received research support from AstraZeneca, Amgen, Eli Lilly, Novartis and is a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, CSL Sequiris, Eli Lilly, GSK, Novartis, Novo Nordisk, Sanofi Pasteur, Vaxxinity. CMB has received grant or research support from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Ionis, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk, Roche Diagnostics, NIH, AHA and ADA and is a consultant for 89Bio, Abbott Diagnostics, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Illumina, Ionis, Eli Lilly, Merck, NewAmsterdam Pharma, Novartis, Novo Nordisk and Roche Diagnostic.
KKR reports Research Grants- Amgen, Sanofi, Regeneron, Daiichi Sankyo, and Ultragenyx to Imperial College London.
Consultancy-Novartis, Daiichi Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, SilenceTherapeutics, AZ, NewAmsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio,Scribe, Crispr, Vaxxinity, Amarin, Regeneron, Ultragenyx, Sanofi Cargene, and Resverlogix.Fees for lectures-Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi,Amgen, Esperion, Daiichi Sankyo, Mankind, Macleod Pharma for symposia at international meetings. Holding stock options from NewAmsterdam Pharma, SCRIBE therapeutics andPemi31.
MS serves as a consultant for and/or has received research support from Lexicon, Amarin, NewAmsterdam Pharma, Silence, Sanofi, Regeneron, and Tourmaline. MS also receives salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2024 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA biopharma, Inc., Arrowhead Pharmaceuticals, AstraZeneca Pharma India, AstraZeneca UK Ltd, Bayer, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, Cleerly, Inc., Colorado Dept of Public Health and Environment, Congress Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd., Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc., HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc, Janssen Research & Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc., Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Nectero Medical, Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham and Women’s Hospital, Thrombosis Research Institute, Tourmaline Bio, Inc, University of Colorado, University of Colorado Denver, University of Pittsburgh, VarmX, Verve Therapeutics, WraSer, LLC.
MD, DK, AH, AJN, MHD, JJPK are employees of NewAmsterdam Pharma and hold stocks or options.
Acknowledgements
These data have been previously presented at the National Lipid Association (NLA) 2025 Scientific Sessions, in Miami, Florida.
Obicetrapib is an experimental/investigational CETP inhibitor that is intended to treat dyslipidemia and is currently not regulatory approved.
20
Therapy Use, Glycemic Control, and Obesity Status among U.S. Adults with Type 2 Diabetes: A Comparison Between 2018 and 2024
Jay Patrick Bae 1, Taylor Ryan 2, Kendra Terrell 1, Christopher Adams 2, Jennifer Peleshok 1, Brendan Limone 2, Fatih Tangi 1, Elizabeth H. Marchlewicz 2
1 Eli Lilly, Indianapolis, IN
2 Veradigm LLC, Chicago, IL
Background:
The American Diabetes Association (ADA) made a major update in the pharmacotherapy guidelines for adults with Type 2 Diabetes (T2DM) in 2019. The revised guidelines recommended selecting patient-centric therapies from the first line rather than following the linear intensification of therapies starting with metformin. It is unclear to what degree T2DM therapies have changed in real-world patients since the guidelines change.
Purpose:
To examine changes in prescribing pattern among real-world patients with T2DM, and their glycemic control and body mass index (BMI) status between 2018 and 2024.
Methods:
This study used Veradigm Network Electronic Health Records (EHR) to analyze medication prescribing patterns, glycemic control, and obesity status among patients diagnosed with T2DM. The multi-year cross-sectional study identified adults active in the EHR for two consecutive years (i.e., baseline year and study year) between 2017 and 2024. Individuals who met this requirement for two consecutive years were subjected to the following inclusion criteria: T2DM diagnosis in the study year with no T1DM diagnosis in the study year or baseline year; minimum 1 HbA1c and BMI measurement in the study year following T2DM diagnosis.
In the study year, anti-hyperglycemic medication (AHM) prescribing was identified via EHR prescription record. Patients receiving multiple AHM classes were represented in multiple drug classes. The last observed HbA1c and BMI measures in each study year were reported. HbA1c was assessed categorically (<6.5%, ≥6.5%-<7%, ≥7%-<8%, ≥8%-<9%, ≥9%). BMI was reported categorically as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obesity class I (30.0-34.9 kg/m2), obesity class II (35.0-39.9 kg/m2), and obesity class III (≥40 kg/m2). For Asians, the BMI cutoffs were adjusted by the WHO definition. Patient demographic and clinical characteristics were obtained from the baseline year.
Out of the 7 years, we selectively reported 2018 and 2024 data focusing on glycemic outcomes and obesity for the overall T2DM patient population and the subset of patients treated with incretins.
Results:
In the EHR, 1,919,968 patients met inclusion criteria in 2018 and 1,291,287 in 2024. Patient characteristics were similar over time, with mean age 63-64 years, 48% male, 60-63% white, and mean Charlson Comorbidity Index of 2.
As for T2DM therapy pattern, metformin usage was 76.8% in 2018 and 64.8% in 2024 but remained the most widely prescribed AHM class; metformin monotherapy share was 30.2% in 2018 and 19.4% of T2D patients in 2024. Sulfonylurea use rate was 32.7% in 2018 and 23.1% in 2024. DPP-4i use rate was 19.4% in 2018 and 12.5% in 2024, and SGLT2i use rate was 11.6% in 2018 vs. 32.3% in 2024. Incretin use rate was 11.7% in 2018 and 41.5% in 2024. Insulin user share remained relatively stable (29.7% to 26.5%) during the period. The proportion of diagnosed but untreated T2DM patients was 21.1% in 2018 but rose to 35.7% in 2024.
In the overall T2DM group, mean (SD) HbA1c was 7.42% (5.18) in 2018 and 7.30% (2.72) in 2024. In 2018 and 2024, patients reporting HbA1c <7% was 44.9% and 49.8%, while patients reporting HbA1c >9% was 16.8% and 13.2%. Obesity prevalence was 64.3% in 2018 and 60.2% in 2024. Dually uncontrolled patients (HbA1c ≥8% and obesity) were 20.9% of T2DM population in 2018 and 15.2% in 2024.
In the metformin monotherapy group, mean HbA1c (SD) was 6.80% (4.42) in 2018 and 6.88% (2.17) in 2024. Patients reporting HbA1c <7% was 60.5% in 2018 and 59.2% in 2024, while HbA1c ≥9% was seen in 5.7% and 4.7% over the same period. In this metformin monotherapy group, 40.8% of the patients had HbA1c of 7% or higher in 2024, which was virtually unchanged from 39.5% in 2018. Obesity prevalence was 62.9% in 2018 and 55.8% in 2024.
In the incretin treated group, mean (SD) HbA1c was 8.10% (6.73) in 2018 and 7.52% (2.91) in 2024. Patients reporting HbA1c <7% was 27.5% in 2018 and 43.9% in 2024, while HbA1c ≥9% was seen in 27.6% and 18.1% over the same period. In this group, obesity prevalence was 79.2% in 2018 to 72.6% in 2024. Patients with obesity class 2 or higher were 51.0% in 2018 and 44.4% in 2024.
Conclusions:
This was a multi-year cross-sectional description of T2DM patient population, their prescribed AHMs, and glycemic and obesity status. Since we did not follow the same patients over time, changes seen between years do not necessarily imply changes are taking place in the same patients over time. Patients receiving multiple therapies belong to multiple groups, too, unless noted otherwise.
We found prescribing patterns in T2DM therapy changed considerably since the ADA pharmacotherapy updates. Use of SGLT2i and the incretin classes increased considerably. This is consistent with the recommendations to optimize therapies based on patients’ risk factors, e.g., ASCVD, HF, CKD, and obesity. Planned additional analyses will examine whether patients with such risk factors are more likely to be prescribed the recommended AHM classes.
Glycemic outcomes have improved in the overall T2DM population. We found the proportion of patients with HbA1c of 8% or higher decreased by 18.8% between 2018 and 2024, while standard deviation of the mean HbA1c shrank from 5.18% to 2.72%. This suggests a big decline in glycemic variability among T2DM patients. Particularly notable in the incretin therapy group, was the proportional shift of the patients with HbA1c ≥9% from 27.6% to 18.1%, meaning more than a third of the patients in the uncontrolled status in 2018 have transitioned to a better controlled state by 2024. Guideline changes, health plan quality metrics in the health care environment, and availability of more effective therapies may have helped improve glycemic control. However, the data show the majority of T2DM patients still do not achieve HbA1c <7% in 2024. Individuals who receive metformin monotherapy are approximately one out of five T2DM patients in 2024, and in this subgroup 40.5% have HbA1c ≥ 7%, virtually unchanged from the 2018 level of 39.5%.
The need to control weight remains a challenge; however, the data showed some positive shifts. The improvement is most apparent in the group receiving incretin therapy but also showing in the overall T2DM. Reducing obesity in T2DM would help improve their cardio-metabolic health and might even reverse the pathophysiology of T2DM in some patients.
Disclosures:
This project was funded by Eli Lilly.
21
Tirzepatide for Weight Management in a Patient with Gastroparesis Secondary to Vagal Nerve Injury: A Case Study
Chau Hoang, PharmD1,2,3, Jacqueline Burke, PharmD3, Giovanna Leddy, MD3, Danbi Choi, NP3
1Boston Medical Center, Brighton, MA, USA
2Massachusetts College of Pharmacy and Health Sciences
3Atrius Health, Watertown, MA, USA
Background:
Tirzepatide is the first and only FDA approved dual incretin receptor agonist (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) for weight loss demonstrating substantial benefit compared to other anti-obesity medications, including those that are GLP-1 receptor agonists alone. Adverse effects between both GLP-1 and GLP-1/GIP receptor agonists are similar, as are the precautions and contraindications to use. One notable adverse effect of these medications is delayed gastric emptying. Medications containing GLP-1 receptor agonists mimic the incretin hormone, GLP-1, in response to food intake, thereby increasing insulin sensitivity, decreasing glucagon production and delaying gastric emptying (GE). Studies have found increased risks of gastrointestinal (GI) adverse events, including gastroparesis, with use of GLP-1 receptor agonists and therefore, use is not generally recommended in those with underlying gastric emptying abnormalities. These medications have not been studied in individuals with pre-existing severe GI disease, including severe gastroparesis. There is concern that use of these medications may exacerbate gastroparesis in individuals with underlying gastric motility disorders. Here, we report the first case of tirzepatide use for weight loss in a patient with a history of severe gastroparesis secondary to vagal nerve injury.
Purpose:
The purpose of this case report is to provide information regarding the use of tirzepatide in a patient with severe gastroparesis. To our knowledge, this is the first reported case of tirzepatide use for weight management in a patient with a history of severe gastroparesis secondary to vagal nerve injury. The need for weight loss in this patient was multifactorial but driven by the need for a surgery to minimize perioperative risk.
Methods:
We present the case of a 57-year-old female referred to the weight management clinic for class II obesity with a complex past medical history including hypertension, obstructive sleep apnea, hypothyroidism, depression, anxiety, post-traumatic stress disorder (PTSD), chronic migraine, osteoarthritis, history of kidney stones, iron deficiency, and recently diagnosed heart failure with preserved ejection fraction (HFpEF). Her initial weight was 356 lb and body mass index (BMI) was 55.65 kg/m2. A weight loss goal of BMI under 50 kg/m² (290 lb) was identified to qualify her for bilateral knee surgery. She had either failed or was contraindicated for other anti-obesity pharmacotherapies. Due to her history of Toupet fundoplication and partial small bowel resection, which resulted in the patient developing severe gastroparesis with profound nausea and vomiting episodes, she was deemed unsuitable for bariatric surgery after evaluation by multiple bariatric teams. Following consultation with a multidisciplinary team including weight management, gastroenterology, nutrition, and clinical pharmacy, the patient agreed to a trial of tirzepatide with close clinical monitoring by the weight management team.
Results:
Because weight loss was required for this patient to qualify for bilateral knee replacement, surgical and pharmaceutical strategies for weight reduction were explored. Since she was unable to pursue a surgical method and had exhausted or was contraindicated to use other non-GLP-1 receptor agonist options, benefits versus risks of use of a GLP-1 medication was considered where it may have otherwise been avoided. A multidisciplinary team evaluated available GLP-1 and GLP-1/GIP receptor agonist options. Tirzepatide was chosen due to duration of action and because of limited availability of semaglutide at the time of prescribing due to shortages. The patient was initiated on tirzepatide 2.5 mg weekly and was able to titrate up to the maximally available dose of 15 mg weekly.
During the course of tirzepatide use, she tolerated treatment well but did not experience any weight loss due in part to fluid retention from newly diagnosed heart failure and food insecurity. She was also admitted to the hospital frequently during the follow up period but never due to use of tirzepatide or a flare of gastroparesis. The tirzepatide was stopped for unclear reasons by the patient as noted during one of her inpatient notes.
Despite lack of therapeutic response, the patient was able to tolerate tirzepatide at maximum dose without significant adverse effects, including no exacerbation of gastroparesis. However, due to the presence of complicating comorbidities, the efficacy of tirzepatide for weight loss in this patient could not be conclusively assessed.
Conclusions:
Patients with obesity are often asked to achieve a 5-10% weight loss, or BMI under 40 kg/m2 prior to elective surgeries to minimize perioperative risk. For this patient, additional benefits could also be realized from weight loss such as improvement in chronic pain, improvement in HFpEF, and improvement in obstructive sleep apnea. Given the need for clinically significant weight reduction and patient’s suboptimal response to previous pharmacologic and lifestyle-based interventions, GLP-1 or GLP-1/GIP receptor agonist represents the most effective pharmacologic for weight reduction among the available options.
We present the first reported case of a patient with severe gastroparesis secondary to vagal nerve injury who was able to tolerate tirzepatide without significant adverse effects. However, due to the presence of complicating comorbidities, the efficacy of tirzepatide for weight loss in this patient could not be conclusively assessed. This case highlights the importance of interprofessional collaboration across healthcare teams and institutions to optimize the management of complex obesity. GLP-1 or GLP-1/GIP receptor agonists should therefore be used with extreme caution and close monitoring in patients with a history of gastric emptying disorders. Further research is needed to clarify the safety and effectiveness of these agents in this high-risk population.
Disclosures:
Nothing to disclose by any authors.
22
The Relationship Between Homocysteine and Vascular Aging in a Health Examination Population Based on Coronary CT Angiography
Zhang Mochou1, Jing Yuan2
1 School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, China
2Shengli Oilfield Central Hospital, Dongying, Shandong 257000, China.
Background:
In recent years, vascular aging has become a crucial target for the early prevention and control of cardiovascular and cerebrovascular diseases. Homocysteine (Hcy), as a potential cardiovascular risk factor, is closely associated with atherosclerosis. However, its relationship with early vascular aging remains unclear. Coronary computed tomography angiography (CCTA) is a non-invasive and accurate technique that can assess the coronary artery wall structure, plaque characteristics and vascular function. It provides an advanced method for quantifying vascular aging. Based on the physical examination population, this study intends to use CCTA to objectively evaluate the state of vascular aging and explore the association between Hcy levels and vascular aging. The aim is to provide imaging evidence for the early identification of populations at high risk of vascular aging and the implementation of interventions.
Purpose:
To investigate the relationship between plasma homocysteine (HY) and vascular aging.
Methods:
A total of 343 participants (172 males and 171 females) who underwent health examinations at the Health Management Center of Shengli Oilfield Central Hospital from January 2022 to December 2023 were enrolled. General clinical data, plasma HCY levels, biochemical indicators, and blood pressure were collected. Coronary artery calcification scores (CACS) were calculated using coronary computed tomography angiography (CCTA) to evaluate vascular aging. Participants were grouped based on CACS severity to analyze trends in indicators. Pearson correlation analysis was used to assess the relationship between CACS and HCY, blood pressure, lipid profiles, and blood glucose. Logistic regression models were employed to evaluate the association between HCY and the risk of vascular aging.
Results:
With increasing CACS, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (GLU), and HCY levels showed a significant upward trend (P < 0.05). Pearson correlation analysis revealed that CACS was positively correlated with age (r = 0.322, P = 0.000), SBP (r = 0.197, P = 0.000), DBP (r = 0.135, P = 0.017), and HCY (r = 0.400, P = 0.000), and negatively correlated with HDL-C (r = -0.144, P = 0.007). Logistic regression analysis demonstrated that HCY remained an independent risk factor for vascular aging across different models adjusted for confounding factors (P < 0.05). ROC curve analysis indicated that HCY had predictive value for vascular aging, with an area under the curve (AUC) of 0.629 (95% CI: 0.571-0.688, P < 0.001). The optimal HCY cutoff was 11.95 μmol/L, yielding a sensitivity of 0.484 and specificity of 0.709.
Conclusions:
In a health examination population, HCY levels are closely associated with coronary artery calcification scores, and HCY exhibits significant predictive value for vascular aging.
Disclosures:
Medical and Health Science and Technology Program of Shandong Province (No. 202003100467)
23
Determinants of Lipid-Lowering Therapy Adherence After Acute Coronary Syndromes in Patients with Cardiometabolic Disease
Katherine A. Tak1, Cassie R. Shao1, Elisa M. Taylor-Yeremeeva1, Carrie R. Shao1, Khanh-Van Tran1, Asem Ali2,3
1 Division of Cardiovascular Medicine, Department of Medicine, UMass Chan Medical School, Worcester, MA
2 Division of Endocrinology and Diabetes, Department of Medicine, UMass Chan Medical School. Worcester, MA
3 Division of Endocrinology, Diabetes, Nutrition & Weight Management. Department of Medicine. Boston University Chobanian & Avedisian School of Medicine. Boston, MA
Background:
Cardiovascular-Kidney-Metabolic Syndrome significantly increases residual cardiovascular risk following acute coronary syndromes. Lipid-lowering therapy (LLT) is critical for secondary prevention; however, adherence remains suboptimal. Using the Transitions, Risks, and Actions in Coronary Events (TRACE-CORE) cohort, we evaluated patient-level determinants of LLT adherence in the context of broader cardiometabolic risk factors.
Purpose:
The purpose of this study is to better understand factors that influence LLT adherence in patients hospitalized for Acute Coronary Syndrome following discharge. This information can help us develop strategies for improving LLT adherence and improving cardiometabolic outcomes.
Methods:
We analyzed 1,200 TRACE-CORE participants (mean age 63.2 ± 10.8 years; 39% female) hospitalized for Acute Coronary Syndrome (ACS) at six hospitals across Massachusetts and Georgia. Baseline demographics, comorbidities, and cardiometabolic risk factors were obtained via structured interviews and medical record abstraction. LLT adherence was assessed at time of discharge, 6, and 12 months. Full adherence was defined as being on LLT at all follow-up interviews, all others were considered partially adherent. Multivariable logistic regression identified independent predictors of partial adherence.
Results:
Overall, 27% of participants were partially adherent to LLT. The overall model was significant (χ² = 22.4, df = 7, p = 0.002). Adherence varied significantly by race (White race (OR 1.62, 95% CI 1.16-2.28, p = 0.006)) and was lower in women than in men (OR 0.69, 95% CI 0.53-0.90, p = 0.005). A history of type 2 diabetes showed a non-significant trend toward greater adherence (OR 1.28, p = 0.087), suggesting a potential gap in secondary prevention for high-risk cardiometabolic patients. In contrast, age, body mass index, chronic kidney disease, and coronary heart disease were not significant predictors.
Conclusions:
In our multicenter ACS cohort, partial LLT adherence was common and disproportionately affected women, racial/ethnic minorities, and patients with T2DM. These findings underscore the need for integrated, patient-centered strategies targeting cardiometabolic disease management to improve LLT adherence and reduce recurrent cardiovascular events.
Disclosures:
Nothing to disclose by any authors.
24
Comparative risk of statin exposure on adverse cardiovascular outcomes in heart transplant recipients
Stephen J. Foley, MD; Shruti Hegde, MD
Affiliations: University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
Background:
The incidence of heart transplantation has increased over time, primarily due to expansions and improvements in donor organ allocation and post-transplant management. However, long-term survival for heart transplant recipients remains affected by the development of a form of rapidly progressive atherosclerosis, known as cardiac allograft vasculopathy (CAV). Along with immunological/inflammatory factors, post-transplant dyslipidemia has been shown to contribute to the pathogenesis of CAV, highlighting the importance of preventative strategies including early implementation of lipid-lowering therapies. Prior studies revealed improved survival and reduced rates of rejection in heart transplant recipients treated with statins. Notably, most recipients require immunosuppressive therapy to prevent acute allograft rejection, although agents such as cyclosporine and corticosteroids may precipitate metabolic dysfunction leading to the rise in LDL cholesterol after transplant. Additionally, current guidelines recommend lower intensity or dosing of statins to reduce the risk of drug-drug interactions with calcineurin inhibitors. As a result, available evidence for LDL-lowering efficacy and cardiovascular outcomes in heart transplant recipients is restricted mainly to low- or moderate-intensity statins, such as pravastatin. Given the risk for drug interactions and statin intolerance, there is a need to investigate alternative antilipemic therapies or combinations with immunosuppressants for CAV prevention in heart transplant recipients.
Purpose:
Briefly, this prospective cohort study using the large global federated electronic medical record database (TriNetX) aims to add to the current literature regarding the perioperative management heart transplant recipients, specifically in relation to the safety and efficacy of statin exposure in preventing CAV and adverse cardiovascular events. Compared to other single-center studies, this study accesses the most current electronic health record (EHR) data from dozens of healthcare organizations (HCOs) to provide a distinctively broad representation of the long-term cardiovascular outcomes after heart transplant across the United States. Moreso, while the beneficial effects of statins on preventing graft failure/dysfunction and CAV in heart transplant recipients has been examined in low- and moderate-intensity groups, this study uniquely includes high-intensity statins within the exposure cohort.
Methods:
A TriNetX query was conducted using EHR data within the US Collaborative Network, including 65 HCOs. Patients aged 18 to 75 years with ICD or CPT codes for diagnosis, procedure, or evaluation related to heart transplant (index event) between January 1, 2015 and December 31, 2024 were included. All study patients were prescribed an immunosuppressant within the first year after the index event (IE). Patients prescribed GLP-1 agonists during the study period were excluded. Cohorts were distinguished based on treatment with or without statins, and the statin group must have been prescribed for at least three instances within the first year after IE. Propensity score matching by baseline demographics (age at IE, race, sex), comorbidities (T2DM, PVD, nicotine dependence), and characteristics (BMI, systolic BP, HbA1c, creatinine, LDL-C) yielded 1,860 subjects within each group. Outcomes were analyzed from 30 days to 10 years following IE. The primary outcome was combined 5-Point Major adverse cardiac event (MACE) (angina/myocardial infarction, stroke, cardiac arrest, heart failure, invasive cardiac procedure). Secondary outcomes included all-cause mortality, cardiovascular disease (CVD), ischemic heart disease, cerebrovascular disease, heart failure, invasive cardiac procedures, and myalgia. Patients with outcomes prior to the follow-up window were excluded from risk calculations.
Results:
Patients in the statin cohort were predominantly White (63.0% vs 61.1%, p=0.237) and male (64.0% vs 62.6%, p = 0.377), and the average age at IE was 48.1 +/- 16.4 years (vs 47.6 +/- 16.5, p=0.374). Notably, the statin cohort reported lower systolic BP (115.7 +/- 24.2 vs 121.0 +/- 24.2, p <0.001) and LDL-C (79.6 +/- 34.2 vs 85.6 +/- 37.1, p <0.001) at baseline. For immunosuppression, most patients were prescribed tacrolimus (49.7% in statin cohort vs 50.3% in non-statin cohort, p = 0.718). In the non-statin cohort, alternative lipid-lowering therapies were omega-3 fatty acids (3.6%) and ezetimibe (3.5%), while PCSK9 inhibitors accounted for less than 0.5%. From this, while having similar comorbidities, the statin group demonstrated an appreciable advantage in baseline vitals and lipid profile prior to study window.
Despite these findings, the risk of any 5-Point MACE occurring during the 10-year follow-up was significantly higher in the statin cohort, RR = 2.688 (95% CI: 2.243-3.220). The statin cohort also experienced higher rates of overall cardiovascular morbidity, RR = 2.545 (95% CI: 2.127-3.045); ischemic heart disease, RR = 2.551 (95% CI: 1.969-3.306); heart failure, RR = 2.581 (95% CI: 2.124-3.137); and invasive cardiac procedures, RR = 4.693 (95% CI: 3.889-5.662). The risk of cerebrovascular events was slightly increased in the statin group, RR = 1.675 (95% CI: 1.202-2.333), but the hazard ratio was insignificant, HR = 1.313 (95% CI: 0.936-1.842). Notably, all-cause mortality was lower in the statin cohort, RR = 0.831 (95% CI: 0.725-0.952). By excluding patients with prior outcomes from analysis, these data highlight higher rates of new onset cardiovascular disease (CVD) or first incidence of MACE but do not account for benefits of continuing statins in the context of pre-existing CVD.
Patients in the statin cohort were more likely to experience the adverse effect of myalgia, RR = 1.576 (95% CI: 1.191-2.086), which may be useful for speculating the burden of statin intolerance. While graft failure was not specifically measured, the impact of drug-drug interactions contributing to worse outcomes appears minimal, as both cohorts were equally prescribed calcineurin inhibitors.
Conclusions:
Similar to nontransplant patients, current guidelines for heart transplant recipients recommend statins as primary therapy to target aggressive and early LDL lowering for the benefit of reduced cardiovascular disease burden. However, the results from this large, propensity-matched cohort study demonstrated no significant all-cause mortality benefit in transplant recipients treated with statins. Instead, the statin group exhibited significantly higher risk of 5-point MACE, cardiovascular disease, ischemic heart disease, new onset heart failure, and invasive cardiac procedures.
Evidently, heart transplant recipients are a unique population and should be considered high risk for CVD even and especially after transplant. It is possible that these patients do not receive the same caliber of preventive therapy with high-intensity statins due to concerns for drug interactions with CNIs and the potential for statin intolerance or discontinuation. However, our data suggest that the poorer outcomes are not impacted by these reactions. Therefore, these findings may benefit from studies comparing outcomes in heart transplant recipients by statin intensity.
These results challenge the consensus on post-transplant CVD risk reduction with statin therapy and indicate a need for further investigation into potential alternative or adjunct therapies, such as PCSK9 inhibitors, to achieve the necessary mortality benefit in these populations.
Disclosures: Nothing to disclose by any authors.
25
Comparative risk of statin exposure on adverse cardiovascular outcomes in kidney transplant recipients
William G. Morrison, MD; Stephen J. Foley, MD; Shruti Hegde, MD
Affiliations: University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
Background:
The prevalence of hypercholesterolemia in post-kidney transplant patients is estimated to be as high as 80%. After transplant, total cholesterol often falls from pre-transplant levels due to improved protein metabolism and lipoprotein clearance. However, lipid levels typically rise again within months of transplant, due to initiation of immunosuppressives (especially calcineurin inhibitors and mTOR inhibitors) and post-transplant metabolic syndrome. Many patients continue to have elevated LDL and triglycerides long-term compared to the general population, and statin therapy is often required chronically. Current guidelines designate statins as the first-line antilipemic in transplant recipients, as prior studies have demonstrated lower all-cause mortality, improved cardiovascular risk profiles, and even reduced graft rejection. Most notably, the Assessment of Lescol in Renal Transplantation (ALERT) trial observed significant reductions in cardiac death and nonfatal myocardial infarction in kidney transplant patients receiving statins; follow-up studies have shown support for these findings.
Purpose:
Briefly, this prospective cohort study using the large global federated electronic medical record database (TriNetX) aims to add to the current literature regarding the perioperative management of kidney transplant recipients, specifically relating to the safety and efficacy of statin exposure in preventing CAV and adverse cardiovascular events. Compared to other single-center studies, this study accesses the most current electronic health record (EHR) data from dozens of healthcare organizations (HCOs) to provide a broad characterization of long-term cardiovascular outcomes after kidney transplant in patients across the United States. Moreover, while the beneficial effects of statins on preventing graft failure/dysfunction and CAV in kidney transplant recipients has been examined in low- and moderate-intensity groups, this study uniquely includes high-intensity statins within the exposure cohort. exposure cohort.
Methods:
A TriNetX query was conducted using EHR data within the US Collaborative Network including 69 healthcare organizations (HCOs). Patients aged 18 to 75 years with ICD or CPT codes for diagnosis, procedure, or evaluation related to kidney transplant (index event) between January 1, 2015 and December 31, 2024 were included. All study patients were prescribed an immunosuppressant within the first year after the index event (IE). Patients prescribed GLP-1 agonists during the study period were excluded. Cohorts were distinguished based on treatment with or without statins, and the statin group must have been prescribed for at least three instances within the first year after IE. Propensity score matching by baseline demographics (age at IE, race, sex), comorbidities (T2DM, PVD, nicotine dependence), and characteristics (BMI, systolic BP, HbA1c, creatinine, LDL-C) yielded 24,139 subjects within each group. Outcomes were analyzed from 30 days to 10 years following IE. The primary outcome was combined 5-Point MACE (angina/myocardial infarction, stroke, cardiac arrest, heart failure, invasive cardiac procedure). Secondary outcomes included all-cause mortality, cardiovascular disease, ischemic heart disease, cerebrovascular disease, heart failure, invasive cardiac procedures, and myalgia. Patients with outcomes prior to the time window were excluded from risk calculations.
Results:
After propensity score matching, patients in both the statin and non-statin cohorts were predominantly White (58.0% vs 56.8%, p=0.006) and male (59.4% vs 59.3%, p=0.831). The average age at index event was 51.6 +/- 12.0 years in the statin cohort vs 51.8 +/- 12.8 years in the non-statin cohort (p=0.123). At the 10-year timepoint following kidney transplant, the risk of any 5-Point MACE occurring was significantly higher in the statin cohort, risk ratio (RR) = 1.881 (95% CI: 1.788-1.980). The statin cohort also experienced similarly elevated risk of overall cardiovascular morbidity, RR = 1.862 (95% CI: 1.769-1.960) and new-onset heart failure, RR = 1.989 (95% CI: 1.876-2.109).
The statin group also exhibited an even greater increased risk for cerebrovascular mortality, RR = 2.370 (95% CI: 2.123-2.647) and need for invasive cardiac procedures, RR = 3.919 (95% CI: 3.482-4.411). Notably, all-cause mortality was not significantly different between groups, RR = 1.016 (0.973, 1.061), though hazard ratio did show some benefit in patients receiving statin therapy, HR = 0.831 (95% CI: 0.725-0.952). Additionally, patients in the Statin group were slightly more likely to be prescribed glucocorticoids, RR = 1.231 (95% CI: 1.217-1.245). Moreover, patients in the Statin group exhibited higher rates of type 2 diabetes (35.5% vs 34.6%, p=0.036), a higher average serum LDL cholesterol (94.0 +/- 43.1 vs 90.6 +/- 39.9, p=<0.001), and a higher HbA1c (6.2 +/- 1.6 vs 5.8 +/- 1.5, p=<0.001).
Conclusions:
In this large, cohort study of kidney transplant recipients, statin exposure was not associated with a reduction in MACE or overall cardiovascular morbidity over a 10-year follow-up. In fact, patients receiving statins demonstrated significantly higher risk of MACE and invasive cardiac procedures compared with non-statin users, despite similar all-cause mortality between groups. Although the risk ratio for all-cause mortality was not statistically significant at 10 years, the lower hazard ratio in statin users suggests an early survival benefit after transplantation that normalizes over time. This pattern likely reflects both a complex interplay of competing risks and possible confounding, as patients in the statin cohort entered transplantation with higher LDL-C, HbA1c, and greater glucocorticoid exposure, factors that both necessitate statin use and predispose to adverse cardiovascular outcomes despite therapy.
Our results underscore the need for careful patient selection and individualized lipid management strategies in kidney transplant recipients rather than routine statin initiation. It is also likely that kidney transplant recipients constitute a unique, high-risk population that require adjunctive or alternative lipid-lowering therapy to achieve optimal cardiovascular benefits similar to non-transplant populations. These findings challenge existing guideline assumptions and underscore the importance of individualized therapeutic strategies in kidney transplant recipients.
Disclosures:
Nothing to disclose by any authors.
26
Comparative risk of statin exposure on adverse cardiovascular outcomes in liver transplant recipients
Benjamin Laliberte, MD; Stephen J. Foley, MD; Shruti Hegde, MD
Affiliations: University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
Background:
Availability of liver transplantation has expanded in recent years due to multiple factors including advances in preserving donor organs, reducing incidence of immune rejection, and improved surgical technique. The increased number of patients living with liver transplants has focused attention on optimizing long-term outcomes after transplantation. Liver transplant recipients have an increased risk of cardiovascular events after transplantation, partly due to elevated risk factors such as dyslipidemia, hypertension, and diabetes. As a result, coronary heart disease has emerged as a significant cause of long-term mortality. Prior studies have focused on modifiable risk factors such as dyslipidemia which is present in 46% of patients 2-years post-transplant despite pre-transplant screening. Previous studies have shown a reduction in overall mortality and improved survival associated with statin use after liver transplant. However, concern for drug-drug interactions and statin intolerance can limit the utilization of statin therapy in liver transplant recipients. Common post-transplant immunosuppressive agents, such as corticosteroids, cyclosporin, and tacrolimus have been linked to impaired statin metabolism. Given these considerations, there is a need for further investigation of optimal management of dyslipidemia in liver transplant recipients to establish clear guidelines.
Purpose:
This prospective cohort study aims to utilize TriNetX, a global federated electronic medical record database, to expand the existing literature surrounding cardiovascular risk modification and long-term outcomes post liver transplant. The safety and efficacy of statin exposure for cardiovascular risk modification will be investigated using medical records from a large network of healthcare organizations. This enabled a more expansive analysis than previous studies which utilized a smaller cohort or were limited to a single center.
Methods:
A TriNetX query was conducted using EHR data within the US Collaborative Network including 64 healthcare organizations (HCOs). Patients aged 18 to 75 years with ICD or CPT codes for diagnosis, procedure, or evaluation related to liver transplant (index event) between January 1, 2015 and December 31, 2024 were included. All study patients were prescribed an immunosuppressant within the first year after IE. Patients prescribed GLP-1 agonists during the study period were excluded. Cohorts were distinguished based on treatment with or without statins, and the statin group must have been prescribed for at least three instances within the first year after IE. Propensity score matching by baseline demographics (age at IE, race, sex), comorbidities (T2DM, PVD, nicotine dependence), and characteristics (BMI, systolic BP, HbA1c, creatinine, LDL-C) yielded 6,645 subjects within each group. Outcomes were analyzed from 30 days to 10 years following IE. The primary outcome was combined 5-Point MACE (angina/myocardial infarction, stroke, cardiac arrest, heart failure, invasive cardiac procedure). Secondary outcomes included all-cause mortality, cardiovascular disease, ischemic heart disease, cerebrovascular disease, heart failure, invasive cardiac procedures, and myalgia. Patients with outcomes prior to the time window were excluded from risk calculations.
Results:
Patients in the statin cohort were predominantly White (72.4% vs 71.9%, p=0.450) and male (66.1% vs 66.2%, p = 0.927), and the average age at IE was 57.6 +/- 10.3 years (vs 57.8 +/- 9.7, p=0.188). Notably, the statin cohort reported a generally poorer baseline metabolic profile with higher HbA1c (6.0 +/- 1.5 vs 5.8 +/- 1.5, p <0.001), LDL-C (96.4 +/- 55.0 vs 85.5 +/- 44.7, p <0.001), and creatinine (1.8 +/- 3.4 vs 1.6+/- 1.8, p <0.001). In the non-statin cohort, alternative lipid-lowering therapies were omega-3 fatty acids (2.2%) and ezetimibe (1.1%), while PCSK9 inhibitors accounted for less than 0.2%. For immunosuppression, most patients were prescribed tacrolimus (64.3% in statin cohort vs 64.8% in non-statin cohort, p = 0.586).
At the 10-year timepoint following liver transplant, the risk of any 5-Point MACE occurring was significantly higher in the statin cohort, RR = 1.839 (95% CI: 1.661-2.036). The statin cohort also experienced higher rates of overall cardiovascular morbidity, RR = 1.890 (95% CI: 1.706-2.094); ischemic heart disease, RR = 2.286 (95% CI: 1.982-2.637); new-onset heart failure, RR = 2.061 (95% CI: 1.834-2.317); and invasive cardiac procedures, RR = 3.269 (95% CI: 2.645-4.040); cerebrovascular morbidity, RR = 2.387 (95% CI: 1.661-2.036). Notably, all-cause mortality was lower in the Statin group, RR = 0.869 (95% CI: 0.810-0.932). Patients in the Statin group were more likely to be prescribed glucocorticoids, RR = 1.181 (95% CI: 1.148-1.214), and experience the adverse effect of myalgia, RR = 1.554 (95% CI: 1.332-1.814).
Conclusions:
The results of this study suggest that while statin exposure is associated with a reduced risk of all-cause mortality, it also demonstrated an increased risk of all other studied outcomes, including the primary outcome of 5-point MACE. These results contrast with the cardiovascular risk reduction associated with statin exposure in the general population and indicate a need for further research into possible mechanisms to explain these findings. By excluding patients with prior outcomes from analysis, the current study focused only on new-onset cardiovascular disease or first incidence of MACE. While this is helpful in isolating outcomes related to transplant, it does not account for the benefits of continuing statin therapy for pre-existing disease. Despite propensity score matching, unmeasured factors may limit understanding of a causal relationship. Further stratification of these results by race and sex is warranted.
Current hepatology guidelines continue to recommend statins as first-line therapy for dyslipidemia. Although statins will likely remain the standard of care for the general population, further research is needed regarding alternative therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for dyslipidemia may be indicated for unique populations such as transplant recipients.
Disclosures:
Nothing to disclose by any authors.
27
Comparative risk of adverse cardiovascular outcomes in heart transplant recipients by statin intensity
Benjamin Price, MD; Stephen J. Foley, MD; Shruti Hegde, MD
Affiliations: University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
Background:
Heart transplant recipients face a high risk of adverse cardiovascular outcomes, including cardiac allograft vasculopathy (CAV), graft failure, and major adverse cardiovascular events (MACE). Dyslipidemia is prevalent in this population, driven by immunosuppressive therapy and metabolic changes, and is strongly linked to accelerated atherosclerosis and poor long-term outcomes. Statins are routinely prescribed post-transplant to lower lipid levels and improve survival in post-transplant patients with current guidelines recommending targeting LDL < 100 mg/dL. Evidence from meta-analyses suggests that statins may also reduce rejection episodes and mortality beyond lipid lowering alone. However, the impact of statin intensity on outcomes remains less clear. While some studies report no significant differences in CAV progression between low and high-intensity statin therapy, both groups often maintain relatively low LDL cholesterol levels, potentially obscuring differential effects. Given the progressive nature of CAV-with incidence rising from 8% at 1 year to nearly 50% at 10 years-understanding the role of statin intensity in mitigating CAV risk and progression is critical. Clarifying this relationship could optimize lipid management strategies and improve long-term graft and patient survival in heart transplant recipients.
Purpose:
Here, this study utilizes the large global federated electronic medical record database (TriNetX) to compare the relative mortality benefit of lipid lowering therapy in heart transplant recipients based on statin intensity. This study accesses the most current electronic health record (EHR) data from dozens of healthcare organizations (HCOs) to provide a distinctively broad representation of the long-term cardiovascular outcomes after heart transplant across the United States. The results of this study are intended to add to the current literature regarding perioperative management of cardiovascular disease in heart transplant recipients.
Methods:
A TriNetX query was conducted using EHR data within the US Collaborative Network including 45 HCOs. Patients aged 18 to 75 years with ICD or CPT codes for diagnosis, procedure, or evaluation related to heart transplant (index event) between January 1, 2015 and December 31, 2024 were included. All study patients were prescribed an immunosuppressant (excluding cyclosporine) within the first year after the index event (IE). Patients prescribed GLP-1 agonists during the study period were excluded. Cohorts were distinguished based on treatment with high-intensity (HI) vs low- and moderate-intensity (LMI) statins, and patients must have been prescribed for at least three instances within the first year after IE. Propensity score matching by baseline demographics (age at IE, race, sex), comorbidities (hypertension, dyslipidemia, T2DM, PVD, nicotine dependence), and characteristics (BMI, HbA1c, creatinine) yielded 797 subjects within each group. Outcomes were analyzed from 30 days to 10 years following IE. The primary outcome was combined 5-Point MACE (angina/myocardial infarction, stroke, cardiac arrest, heart failure, invasive cardiac procedure). Secondary outcomes included all-cause mortality, cardiovascular disease, ischemic heart disease, cerebrovascular disease, heart failure, invasive cardiac procedures, and myalgia. Patients with outcomes prior to the time window were excluded from risk calculations.
Results:
Patients in the HI statin cohort were predominantly White (62.5% vs 62.4%, p=0.959) and male (73.7% vs 73.3%, p = 0.865), and the average age at IE was 56.1 +/- 11.4 years (vs 57.0 +/- 11.7, p=0.110). Prior to heart transplant, the baseline metabolic profile was similar between the HI vs LMI cohorts: BMI 28.1 +/- 5.6 vs 27.7 +/- 5.0 (p=0.221), LDL-C 83.4 +/- 39.3 vs 80.7 +/- 34.4 (p=0.172), and systolic BP 122.2 +/- 22.9 vs 120.8 +/- 24.0 (p=0.322). For immunosuppression, most patients were prescribed tacrolimus (66.4% in HI cohort vs 68.6% in LMI cohort, p = 0.336).
At the 10-year timepoint following heart transplant, there was no significant difference in risk of any 5-Point MACE occurring in the HI vs LMI cohorts, RR = 0.918 (95% CI: 0.609-1.383). Similarly, there was no significant difference in risk of secondary outcomes including: all-cause mortality RR = 0.913 (95% CI: 0.732-1.138), cardiovascular disease RR=0.722 (95% CI: 0.491-1.062), ischemic heart disease RR=1.027 (95% CI: 0.696-1.515), cerebrovascular disease RR=1.539 (95% CI: 0.860, 2.756), heart failure RR=1.050 (95% CI: 0.709-1.556). However, the risk of invasive cardiac procedures was significantly lower in the HI cohort, RR=0.736 (95% CI: 0.590-0.918). Also, the hazard ratio for cardiovascular disease was significantly lower, HR=0.717 (95% CI: 0.556-0.924). By excluding patients with prior outcomes from analysis, these data highlight higher rates of new onset cardiovascular disease (CVD) or first incidence of MACE but do not account for benefits of continuing statins in the context of pre-existing CVD.
Interestingly, the HI cohort was less likely to report the adverse effect of myalgia, RR = 0.478 (95% CI: 0.313-0.732). This may be attributed to the observed lower rates of statin intolerance in patients prescribed rosuvastatin due to its water solubility leading to reduced penetration and accumulation in muscle tissue.
Conclusions:
In heart transplant patients, higher intensity statin therapy was not associated with a statistically significant reduction in any 5-Point MACE, all-cause mortality, cardiovascular disease, ischemic heart disease, new onset heart failure or cerebrovascular disease. These findings were examined despite the perceived lower rates of myalgia as a surrogate marker for statin intolerance, suggesting that the HI cohort may have recorded lower rates of statin discontinuation.
Nonetheless, heart transplant recipients are a uniquely high-risk population that require special considerations when determining the appropriate and effective regimen for preventing CAV. Evidently, these results challenge the consensus of preferring low- or moderate- intensity statins after heart transplant out of caution for drug-drug interactions with certain immunosuppressants, when in fact statin intensity had no impact on observed post-transplant outcomes. Future randomized control studies are warranted to confirm and elucidate the mechanism for these findings. Regardless, the lack of benefit from higher intensity statins in this study indicates an opportunity for further investigation of alternative or adjunct lipid-lowering therapies in these patients to achieve adequate post-transplant cardiovascular risk reduction.
Disclosures:
Nothing to disclose by any authors.
28
Understanding Cardiovascular Risk Awareness and Intervention Preferences Among Sedentary Employees in Karachi, Pakistan
Samina Akhtar1, Aysha Almas1, Zainab Samad1, Gerald S. Bloomfield2, Salim S. Virani1, Khairulnissa Ajani1
1Aga Khan University, Karachi, Pakistan
2Duke Global Health Institute, Duke University, USA
Background:
Physical inactivity and unhealthy dietary patterns are major modifiable drivers of cardiovascular disease (CVD) morbidity and mortality worldwide. In South Asian settings, rapid urbanization, sedentary occupations, and shifts toward energy-dense diets have accelerated the cardiometabolic burden. Office-based workers who spend prolonged periods sitting such as bank employees face high risk due to occupational sedentary behavior, long working hours, and workplace stressors that hinder healthy lifestyles. Despite the occupational vulnerability of this group, few context-specific interventions have been developed or evaluated in Pakistan. Workplace interventions that are feasible, acceptable, and tailored to employees’ preferences are required to improve uptake and sustainability. This study explored bank employees’ awareness of CVD risk, beliefs and perceptions about risk and prevention, existing workplace supports, and preferences for CVD prevention interventions to inform the co-design of a contextually relevant, scalable program.
Purpose:
The study aimed to: (1) explore awareness and perceptions of CVD risk among bank employees in urban Karachi; and (2) identify employee preferences for workplace CVD prevention interventions to inform the development of a culturally and contextually tailored mHealth-supported intervention for sedentary employees in Karachi, Pakistan.
Methods:
This exploratory qualitative study is part of the m-LIfE (mobile-based Lifestyle Intervention for Employees), a pilot cluster randomized controlled trial (NCT06981247) focused on developing and testing contextually relevant CVD prevention strategies. Bank employees aged 20-65 years across 3 bank organizations (1 public and 2 private) were purposively selected. Employees with self-reported CVD were excluded. Data were collected from focus group discussions (FGDs, n=6, 34 participants) and in-depth interviews (IDIs) (n=9) between April and June 2025. IDIs were conducted with employees in leadership positions. A semi-structured guide informed by the Health Belief Model was used. All interviews and FGDs were audio-recorded, transcribed verbatim, and thematically analyzed using Braun and Clarke’s six-step approach. We used inductive and deductive approaches to ensure both theory-informed and data-driven insights.
Results:
Participant characteristics: Among FGD participants, 60% were male, with a median age of 37 years (range: 27-60) and a median work experience of 7 years (range: 2-20). Among IDI participants, 66% were male, with a median age of 40 years (range: 35-51) and median work experience of 13 years (range: 8-20). Most participants held a master’s degree.
Four major themes emerged: (1) Awareness (Knowledge of specific behaviors/factors): Participants demonstrated moderate awareness of CVD risks and acknowledged banking as a high-risk profession due to prolonged sitting and job-related stress. However, a consistent gap was observed between knowledge and actual health behaviors, primarily due to time constraints and competing priorities. (2) Perceptions (Interpreting or expressing personal beliefs): Participants attributed CVD risk to urban lifestyles, poor dietary habits, and physical inactivity. Many cited dual-income households, where both husband and wife are working as barriers to healthy living. Occupational stress was widely reported, with participants highlighting performance pressure, job demands, customer-driven stress, long working hours, and a deadline-driven culture where customer needs were prioritized above employee well-being. (3) Existing Workplace Initiatives: While banks occasionally organized health campaigns, typically in response to acute situations such as COVID-19, none addressed long-term strategies for promoting physical activity or healthy eating. (4) Preferences for CVD Risk Prevention Interventions: Participants preferred low-burden, context-sensitive interventions such as digital health applications featuring goal-setting, reminders, dietary guidance on calories, and real-time progress tracking. In-person sessions were preferred initially, followed by tech-based tools such as mobile apps and wearable devices. Paper-based approaches were largely dismissed. Structural suggestions included providing gym equipment at work, extending lunch breaks, and offering health-related incentives.
Conclusions:
Bank employees in urban Karachi are aware of CVD risks but encounter significant psychosocial and structural barriers to adopting healthier behaviors. They prefer interventions that are minimally disruptive, digitally enabled, and embedded into workplace routines combined with initial in-person engagement and organizational support. These findings support the co-design of a behaviorally informed, context-tailored workplace CVD prevention program that pairs low-effort digital tools with feasible structural changes (e.g., protected breaks, on-site facilities, incentive mechanisms). Implementation should prioritize managerial buy-in, and ease of use to promote reach and sustainability. Future work will pilot the co-designed intervention within the m-LIfE trial to evaluate feasibility, acceptability, and efficacy on physical activity, and dietary behaviors.
Disclosures:
This work is supported by the Fogarty International Center (FIC) of the National Institutes of Health (NIH) under Award Number D43TW011625.
29
Burden of Cardiovascular Risk Factors and Estimated 10-Year Risk Among Sedentary Employees in Karachi, Pakistan
Samina Akhtar1, Aysha Almas1, Zainab Samad1, Gerald S. Bloomfield2, Salim S. Virani1, Khairulnissa Ajani1
1Aga Khan University, Karachi, Pakistan
2Duke Global Health Institute, Duke University, USA
Background:
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with low- and middle-income countries (LMICs) bearing the greatest burden. In Pakistan, non-communicable diseases account for nearly 60% of deaths, with CVDs contributing the largest share. Several risk factors including hypertension, diabetes, obesity, dyslipidemia, smoking, and physical inactivity are prevalent in Pakistan. South Asians, including Pakistanis, are further predisposed to early onset CVD due to genetic and lifestyle factors. The rapid pace of urbanization has accelerated adoption of sedentary behaviors and dietary changes that contribute to rising CVD prevalence. Sedentary occupations, particularly those requiring prolonged sitting, are an emerging concern given their association with physical inactivity, obesity, and cardiometabolic risk. Bank employees are at-risk group, as their job responsibilities often involve extended desk work, long working hours, and work-related stress.
Purpose:
This study aimed to (1) assess the prevalence of behavioral and metabolic CVD risk factors and (2) estimate 10-year and lifetime CVD risk among bank employees in urban Karachi, Pakistan.
Methods:
A cross-sectional study was conducted among 371 bank employees aged 20-65 years, with at least 6 months of work experience. They were randomly selected from different branches of one public and two private commercial banks across Karachi. Individuals with prior history of CVD (myocardial infarction, stroke, or coronary artery disease) were excluded.
Data were collected using the WHO STEPS instrument (v3.2), which captured demographic characteristics (gender, age, education, marital status, occupation, and household income), behavioral risk factors (tobacco use, alcohol consumption, diet, salt intake, physical activity, and sedentary behavior), and medical history (hypertension, diabetes, dyslipidemia). Questions for the INTERHEART Risk Score, including those on psychosocial stress, were also administered. Physical measurements included height, weight, waist circumference, and blood pressure. Fasting blood glucose and total cholesterol were measured in consenting participants.
CVD risk was estimated using the 2019 WHO South Asia laboratory- and non-laboratory-based prediction charts for participants aged ≥40 years, while the INTERHEART score was applied to those aged <40 years.
Results:
Of the 371 participants, mean age was 39.7 ± 10.3 years, with 54% <40 years and 79% male. Most participants were married (72%) and had completed university-level education (52%). Behavioral risk factors: 22% were current smokers, 19% used smokeless tobacco, and 4% reported alcohol use. Fruit and vegetable consumption was low, on average one serving per day. Nearly all participants (95.6%) reported always adding salt in cooking, while 19% frequently consumed processed foods high in salt. Physical inactivity was widespread: 71.2% did not meet the recommended 600 MET-min/week, with an average sitting time of 9.8 hours/day.
Metabolic risk factors: Based on South Asian cut-offs, 64% were obese (BMI ≥25) and 14% overweight (BMI 23-24.9). Abdominal obesity was present in 72% of males (WC >90 cm) and 75% of females (WC >80 cm). Raised fasting blood glucose (>126 mg/dl) was observed in 43% (159/230), with 39% of these <40 years. High cholesterol (>240 mg/dl) was found in 42% (155/230). Hypertension management was suboptimal: among those diagnosed (26%), only 31% had controlled BP despite medication use.
CVD risk: ≥40 years: Using WHO lab-based charts, 12.7% (13/102) had moderate risk and 3% high risk of 10-year CVD. Non-lab charts showed 18.2% (31/170) moderate risk. No participants were classified as very high risk.
For participants <40 years (n=201), the INTERHEART score showed 41% at moderate lifetime risk and 12% at high risk. Female participants were more likely than males to fall into the moderate-risk category, while high risk was more common among males.
Conclusions:
This study demonstrates a high burden of behavioral and metabolic CVD risk factors among sedentary bank employees in Karachi. Obesity, physical inactivity, tobacco use, and poor dietary practices were prevalent, while raised blood glucose and cholesterol levels were common even in younger employees. Risk prediction analysis revealed that nearly one in five participants over 40 years was at moderate-to-high 10-year risk of CVD, while a substantial proportion of younger employees were already at elevated lifetime risk.
The study’s limitations include a male predominance, restricting gender-specific analyses, and reliance on self-reported measures for diet, physical activity, and sedentary time.
Nonetheless, these findings highlight the need for workplace-based CVD prevention strategies, including promotion of physical activity during work hours, healthy eating initiatives, stress management programs, and regular health screenings.
Disclosures:
This work is supported by the Fogarty International Center (FIC) of the National Institutes of Health (NIH) under Award Number D43TW011625.
30
Social Determinants of the Cardiometabolic Health of Indigenous Youth: A Systematic Review
Peter Pham, University of California, Berkeley
Dixie Blumenshine, University of California, San Francisco
Rayann Elka Medina, California State University, East Bay
Erika Salinas, California State University, Sacramento
Sky Harper, Medical University of South Carolina
Lindsay T. Hoyt, Fordham University
Alison K. Cohen, University of California, San Francisco
Background:
Indigenous Americans are a medically under-researched group, and manage significant cardiometabolic health issues. They can be conceptualized as a political designation (i.e. Tribal nation citizens), racial category, or ethnicity that can include Native Americans, American Indians, Alaska Natives, and Native Hawaiians. Indigenous Americans experience higher prevalence of cardiometabolic conditions. They also encounter higher morbidity and mortality from those conditions. For example, national data suggests obesity prevalence among Indigenous Americans hovers around 40% compared to 26% for non-Hispanic whites. Adolescence and emerging adulthood is when many cardiometabolic health issues can emerge, with implications for across the lifespan. This developmental window presents an ideal opportunity to identify risk and protective factors to further advance Indigenous Americans’ cardiovascular health, which is crucial because Indigenous youths often have onset of cardiometabolic diseases sooner than non-Hispanic white peers and the general US population.
Many social determinants of cardiometabolic health for other populations in the US are experienced at a higher prevalence among Indigenous Americans. For example, Indigenous Americans encounter low incomes at roughly twice the national rate. Likely in part due to their highly minoritized status, Indigenous Americans are often not studied specifically, limiting understanding about strategies to promote and protect Indigenous American health.
Purpose:
Given the chronic nature of cardiometabolic conditions, there is a need to understand the risk and protective factors that influence their prognosis and the disease burden on patients. Indigenous Americans, in particular, encounter unique challenges in the healthcare system that make it difficult to resolve complex conditions. These include geographic isolation for many communities, chronic underfunding of Indian Health Service, and historically-rooted mistrust. Therefore, we aim to synthesize the literature regarding the risk and protective social determinants of Indigenous American youths’ cardiometabolic health. Social determinants include socioeconomic position, access to healthy food, insurance status, and community and cultural connection. Via this work, we will fulfill a vital need in the current state of understanding on Indigenous American health.
Methods:
We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to systematically search the PubMed and CINAHL databases. We then did an initial review for manuscript relevance based on title and abstract. From there, we screened full texts. All imported articles’ reference lists were cross-screened to ensure relevant references had been included in initial search, and those not initially included were imported. Multiple reviewers screened articles at both stages to ensure quality control. Inclusion criteria were studies that took place within the US, studied Indigenous American participants between 10-30 years of age, and included measurement of statistical association between at least one measure of a social determinant of health and at least one cardiometabolic health measure. We are using the Risk Of Bias In Non-Randomized Studies of Exposures (ROBINS-E) tool to assess bias.
Results:
The initial search returned 4945 non-duplicate articles. After title and abstract screening, which advanced only articles that may have any relevant data, 822 articles were moved forward to a full text screening, representing 16% of all returned articles. Following full text screening, 19 articles, or 2% of all imported studies, appear to meet the criteria for inclusion in the systematic review. Preliminary findings among the included studies suggest that influential social determinants of cardiometabolic health in Indigenous American youths are family income, socioeconomic position, neighborhood poverty, and stress. These observations are consistent with other minoritized groups. However, the literature is lacking on several social determinants of health, including enrollment in a Tribal nation, educational experiences, and residential environment (i.e. urban, suburban, exurban, rural, reservation). This paucity prevents conclusive observations.
Conclusions:
There is a scarcity of literature regarding the impact of social determinants of health on the cardiometabolic health of Indigenous American emerging adults and adolescents. This paucity is likely due to a combination of low representation of Indigenous Americans in the health sciences, their relatively smaller size in the national population, and past harms in research that has fostered a general mistrust of medical institutions and continues festering into research recruitment. As a result, the American healthcare system’s capacity to comprehensively and effectively address the health needs and conditions of Indigenous Americans remains limited. At the same time, social determinants of health remain powerful drivers of health outcomes, making them even more impactful to understand in the context of cardiometabolic conditions’ chronicity and complexity. By understanding these social determinants, healthcare systems can more efficiently allocate resources, effectively prevent disease and deliver care, and ease overall long-term social burden. Moreover, leveraging social determinants can also help the American healthcare system fulfill its legal obligations to provide healthcare to federally recognized Tribes and bridge inequities created and perpetuated over time. Complete findings are pending complete data extraction and interpretation of eligible texts.
Disclosures:
Nothing to disclose by any authors.
31
Impact of Sleep on Body Composition in Adolescents: Moderation Between Diet and Physical Activity
Silverstone. E, Nepocatych. S, Weaver. M
Department of Exercise Science & Department of Mathematics & Statistics, Elon University, North Carolina, USA
Background:
Sleep, diet, and physical activity are essential components of a healthy lifestyle. Lower physical activity levels and poor dietary habits may contribute to the development of cardiovascular disease and metabolic syndrome. Adolescence is a critical period for cardiometabolic health and chronic disease prevention, as adolescents become more independent and establish lifestyle behaviors that often persist into adulthood. Research suggests that most adolescents do not get the recommended amount of sleep; for example, the average college student sleeps less than seven hours per night. Better sleep quality has been shown to improve eating habits and physical activity levels, whereas inadequate sleep can lead to lower physical activity and unhealthy eating behaviors. Poor sleep can also increase the risk of cardiovascular disease by promoting inflammation, weight gain, and hormonal dysregulation. Previous research has identified a positive association between poor sleep and obesity in young adults. However, few studies have examined how sleep, diet, and physical activity together influence early cardiometabolic risk during adolescence, a period when lifelong habits are being formed.
Purpose:
We anticipated that poor sleep would be associated with increased body fat mass and that lower levels of physical activity and poor diet would influence this relationship. The purpose of this study was to examine how poor sleep habits impact body fat mass and to explore the moderating roles of diet and physical activity in adolescence. By understanding these relationships, we can help mitigate the risks of developing cardiovascular disease and metabolic syndrome and promote healthier lifestyle habits in this population. As adolescents transition into college and become more independent, fostering healthier lifestyle habits earlier may be more beneficial for prevention rather than retroactively attempting to change established behaviors.
Methods:
This longitudinal study recruited adolescents aged 17-19 years (n = 227; 70.5% female). Assessments took place during participants’ senior year of high school or first year of college. Sleep regularity, efficiency, and duration were measured using an ActiGraph GT9X Link accelerometer, and sleep satisfaction was assessed using the Pittsburgh Sleep Quality Index (PSQI). Body composition was measured using Dual-energy X-ray Absorptiometry (DXA). Sedentary behavior and physical activity ratio were assessed using activPAL monitors, and dietary habits were assessed using the Automated Self-Administered 24-hour Dietary Assessment Tool (ASA-24). Linear mixed models were used to examine the relationship between sleep and body composition, and moderation analyses tested whether physical activity and diet moderated this relationship. Statistical significance was set at p < 0.05.
Results:
Sleep duration (β = -0.11, p = 0.85), sleep efficiency (β = -2.65, p = 0.51), sleep disturbance (β = 0.08, p = 0.14), and sleep impairment (β = 0.04, p = 0.60) were not significantly associated with fat mass. Similarly, sleep duration (β = -0.47, p = 0.13), sleep efficiency (β = -3.33, p = 0.11), sleep disturbance (β = -0.04, p = 0.13), and sleep impairment (β = -0.02, p = 0.47) were not significantly associated with lean body mass. However, biological sex was a significant predictor of fat mass, with females having on average 4.8 kg higher fat mass than males (β = 4.76, p = 0.019). Higher moderate-to-vigorous physical activity (MVPA) was significantly associated with higher lean body mass (β = -0.04, p = 0.02), and higher sleep disturbance was associated with higher percent body fat (β = 0.09, p = 0.04). The Healthy Eating Index (HEI) score was not significantly related to body composition (β = -0.04, p = 0.39). Biological sex was a significant covariate in nearly all models tested.
Conclusions:
Our preliminary results show a lack of evidence for a relationship between poor sleep and body fat mass, suggesting that sleep alone during adolescence is not a strong predictor of body composition and that other factors likely contribute to changes in body composition. Even after controlling for physical activity and diet, the relationship between sleep and body composition was further reduced, suggesting that these lifestyle factors may mitigate the impact of poor sleep. Remaining physically active and maintaining high cardiorespiratory fitness is important, as it improves cardiovascular health even in individuals who may be considered overweight or obese. High fitness levels can help compensate for some of the negative effects associated with obesity, thereby lowering the risk of cardiovascular disease. Additionally, a diet rich in fruits and vegetables while limiting added sugars, saturated fats, and trans fats can greatly reduce the risk of developing cardiovascular disease. These findings suggest that interventions at supporting healthy body composition and reducing risk of future cardiometabolic disease during adolescence may be more effective when they address multiple lifestyle factors including physical activity, diet and sleep, while also taking sex-specific differences into account.
Disclosures:
Nothing to disclose by any authors.
32
GIANT Lifestyle Changes-One Play at a Time
Andrea Espinoza, MD, FCCP, DipABLM – OCSM Healthcare
Taylor Copelin, MBS – OCSM Healthcare
Background:
Integrating lifestyle medicine changes as suggested by the American Heart Association/American College of Cardiology remains is pivotal to providers truly impacting their patients’ health. However, time constraints of both patients and providers in both seeking and finding feedback for these lifestyle changes can have its limitations.
Patients often lament at referrals to nutritionists and may have limitations to gym membership or poor access to cardiac focused rehabilitation programs.
Integrating real time feedback when patients provide blood pressure logs, food logs, and daily step counts can have a significant impact on patients feelings seen and in control of their health. The result of a single clinic’s communication weekly with a patient and their caregivers demonstrates a unique opportunity to improve cardiovascular conditioning, decrease, inflammatory and poor nutritional choices, improve blood pressure, and decrease patient weight.
Biomarkers observed through routine bloodwork can demonstrate significant changes in prediabetic and diabetic status further decreasing patients cardiovascular risks.
We propose and demonstrate a “game plan” aimed at an individual patients’ understanding of the importance of whole food, plant based nutrition, daily movement, and optimal sleep in decreasing blood pressure and HgbA1C. Patients are looking for the LONG game of sustainable change.
Purpose:
The purpose of this abstract is to highlight the ease of integration in both education and implementation of lifestyle changes, when approaching patients in a more “whole body medicine” fashion. The recommendations according to the American Heart Association and the American College of Cardiology suggests that patients embrace improved nutrition, movement and sleep to decrease cardiovascular risk factors. As such, during initial and follow up clinic visits aimed at optimizing these three distinct pillars of intervention we have found that patient feedback with blood pressure logs, food logs and daily step logs can have a significant impact on patient’s measured outcomes. We have found that patients are motivated by real time, communication via email, as well as ease in access to phone conversations with a provider, focusing on being “in the game and on the same team” of lifestyle changes with patients.
Methods:
Any labs obtained within a previous three month period are documented and reviewed with patient. Current medications are confirmed and documented. Patients confirm adherence to current medications.
If appropriate, for OSA up workup, a home sleep test is ordered. Results of baseline labs and subsequent sleep test are reviewed in detail with patient and their caregiving team.
Patients then have a session with the lifestyle medicine team to review 5 day blood pressure and 5 day food log.
Education regarding whole foods plant-based is done and patients have the opportunity to engage with the team for no less than 30 minutes during which time both food shopping recommendations, food preparation, as well as foods to avoid are carefully outlined.
Patients are also assessed for safety regarding gait and balance, and asked to obtain a low cost Fitbit device or other pedometer device, which to self record daily step count.
Patients are asked to watch “Plant Pure Nation” documentary as a baseline for their understanding of the potential for health improvement through lifestyle changes.
Patients are assessed at biweekly phone and or in person clinic visits to ascertain responses to blood pressure, daytime, energy, improvement, and step count.
Results:
The patient presented to the clinic for an obstructive sleep apnea assessment with a history of hypertension, hyperlipidemia, and Type II diabetes mellitus. The patient also presented with a significant cardiac history, as he had a Quadruple Coronary Artery Bypass Graft in 2011. Patients initial vital metrics in clinic were a weight of 276 lbs and a blood pressure of 127/79 mmHg. Following 3 months of lifestyle interventions, the patient’s weight on 08/20/2025 was 243 lbs, and his blood pressure was in an clinic reading of 118/82 mmHg. BMI decreased from 36.41 to 32.59.Patients initial lab work May 7th 2025 revealed a HbgA1c of 6.5% and a fasting glucose of 131 mg/dL. Labs drawn three months later indicated a HgbA1c of 5.7% and a fasting glucose of 117 mg/dL. Patient was able to discontinue isosorbide and lisinopril due to low blood pressures that resulted in a fall. He de-escalated his metformin to 500 mg 4 days a week. Patient remained compliant with his CPAP during these 3 months in order to optimize sleep, and noted significant improvement in his overall sleep quality. Patient was able to increase activity and energy levels with diet and exercise changes. Patient cut out all soda from diet, and moved toward a more whole food, plant based diet. Patient incorporated watermelon, strawberries, cantaloupe, and blueberries in his daily snack rotation to decrease inflammation. He also avoided all fast foods, and was encouraged by calls and emails from the lifestyle team. Patient kept a treadmill log showing a steady increase in his physical abilities, reaching 30 minutes per day and averaging 1.5 miles. His overall mood and engagement in his healthcare plan was improved and he reported a subjective increase in quality of life. An avid New York Giants football fan, he reported feeling grateful for the TEAM approach to his health game plan.
Conclusions:
Being truly in the game of individualized patient care requires a provider’s willingness to be on the field with them. “Watching film” means giving patients an opportunity to see that the goal of guidelines and recommendations is truly personal.
THEIR individual statistics matters to them-not “how many Americans die of heart disease each year”, but rather whether or not THEY succumb to heart disease.
The pillars of lifestyle medicine-nutrition, physical activity, stress reduction, avoidance of harmful substances, restorative sleep and community can ALL be attained by the program outlined in this abstract.
For many patients, they are less apt to admit if they are making poor nutritional choices during fast paced and routine primary care follow up. However, when asked to document their food, and/or harmful substance intake, they are more willing to sit and learn about food choices that may positively impact their health. Optimizing patients’ sleep is also crucial to providing both physical and mental reserve for patients to engage in daytime physical activity.
Stress reduction and improvement in patient’s health education results in knowledge and pride as they meet daily step counts goals. Having a patient hear from their care team by phone or email biweekly is both motivating and contributory to sustained health changes and builds the COMMUNITY of patient provider relationships.
Disclosures:
Nothing to disclose by any authors.
33
Semaglutide improves liver health and cardiovascular outcomes among patients with cardiovascular disease at risk of metabolic dysfunction-associated steatohepatitis
Sebastian M. Meyhöfer1,2; Ole Kleist Jeppesen3; Mette Skalshøi Kjær3; A. Michael Lincoff4; Ildiko Lingvay5; Philip N. Newsome6; Steven E. Kahn7; María De Los Angeles Quiroga Peláez3; Ferruccio Santini8; Arun J. Sanyal9
1Clinical, Medical & Regulatory, Novo Nordisk Pharma GmbH, Mainz, Germany
2Department of Internal Medicine 1 – Endocrinology & Diabetes, University Medical Centre Lübeck, Lübeck, Germany
3Novo Nordisk A/S, Søborg, Denmark
4Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
5Department of Internal Medicine/Endocrinology and Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
6Institute of Hepatology, King’s College London and King’s College Hospital, London, UK
7Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA
8Obesity and Lipodystrophy Centre, University Hospital of Pisa, Pisa, Italy
9Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Background:
Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for adverse cardiovascular (CV) outcomes among patients with obesity. Noninvasive tests, such as the Fibrosis-4 (FIB-4) score, are increasingly used in clinical settings to assess fibrosis severity and stratify patients with MASH by risk of overall, CV-related, and liver-related mortality. Several clinical trials are investigating treatments for MASH that target cardiometabolic risk factors and reduce the incidence of adverse clinical outcomes. The SELECT trial, which evaluated CV outcomes, found that treatment with semaglutide 2.4 mg-a glucagon-like peptide-1 analogue-led to a 20% lower risk of major adverse CV events (MACE) compared with placebo in patients with a body mass index ≥27.0 kg/m2 and established CV disease but no history of diabetes. However, less is known about the impact of semaglutide on markers of liver health and among patients with increased risk of MASH.
Purpose:
Further research is needed to elucidate the relationship between semaglutide treatment and improvements in CV and liver health among patients with overweight or obesity and established CV disease. The present study evaluated the effects of semaglutide on liver enzymes and predicted hepatic steatosis in SELECT study participants. Additional analyses assessed whether semaglutide treatment conferred a CV benefit to a subgroup of SELECT study participants at high risk for MASH, as defined by FIB-4.
Methods:
SELECT, a multicenter, randomized, double-blind, placebo-controlled, event-driven trial, enrolled 17,604 patients aged ≥45 years. Patients were randomized (1:1) to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo in addition to the recommended standard of care for CV disease prevention. This study assessed changes in levels of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), as well as the fatty liver index (FLI)-an algorithm based on body mass index, waist circumference, triglycerides, and GGT predictive of hepatic steatosis-over 104 weeks. A subgroup analysis was conducted to evaluate the risk of 3-point MACE (a composite of nonfatal myocardial infarction, nonfatal stroke, and CV-related death) among patients at risk of MASH. Increased MASH risk was defined as FIB-4 ≥1.3 for patients aged <65 years and FIB-4 ≥2.0 for those aged ≥65 years, excluding patients with other causes of liver disease.
Results:
In the overall SELECT cohort, semaglutide treatment induced a rapid decline in ALT, AST, and GGT levels, with the lowest values observed at 20 weeks after the initiation of treatment. After this nadir, levels of ALT and AST slightly increased over time, while GGT remained stable. At week 104, the estimated treatment difference vs placebo for ALT, AST, and GGT was −1.9 U/L (95% CI, −2.6 to −1.2; P<0.0001), −0.9 U/L (95% CI, −1.3 to −0.5; P<0.0001) and −8.2 U/L (95% CI, −9.5 to −6.8; P<0.0001), respectively. Compared with patients receiving placebo, patients treated with semaglutide experienced a 6% (95% CI, 0.93-0.95; P<0.0001) greater decrease from baseline in ALT levels, a 3% (95% CI, 0.96-0.98; P<0.0001) greater decrease in AST levels, and a 17% (95% CI, 0.82-0.84; P<0.0001) greater decrease in GGT levels. Treatment with semaglutide also led to a decrease of 16.1 (95% CI, −16.7 to −15.6; P<0.0001) in FLI vs placebo, corresponding to a 28% greater decrease in FLI (95% CI, 0.71-0.73; P<0.0001). While patients receiving placebo had a −0.88% mean change in body weight over 104 weeks, patients treated with semaglutide experienced a −9.39% mean change in body weight.
Nearly 21% of the overall SELECT cohort-3,664 patients aged <65 years with FIB-4 ≥1.3 and aged ≥65 years with FIB-4 ≥2.0-were identified as having a high risk of MASH. Among the 3,664 patients with high risk of MASH, 1,833 of those treated with semaglutide (7.6%) experienced MACE compared with 1,831 of those receiving placebo (9.6%). Thus, treatment with semaglutide 2.4 mg resulted in a 21% lower risk of MACE in this subpopulation at high risk for MASH (hazard ratio, 0.79; 95% CI, 0.63-0.98; P<0.03).
Conclusions:
In the absence of diabetes, patients with obesity or overweight and established CV disease showed significant and rapid improvement in liver enzyme levels and FLI following treatment with semaglutide. A high percentage of patients with MASH are living with obesity, and MASH is associated with an elevated risk of CV disease. Among a subgroup of patients identified as having high risk of MASH as defined by FIB-4, semaglutide significantly mitigated CV risk, consistent with the 20% risk reduction seen in the overall SELECT study population. These findings suggest that treatment with semaglutide not only improves liver health in patients with obesity or overweight and established CV disease but also reduces CV risk in a subset of patients at high risk for MASH.
Disclosures:
Sebastian Meyhöfer has received consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daichii-Sankyo, esanum, Eli Lilly, Gilead, Ipsen, Novartis, Novo Nordisk, Sandoz, and Sanofi; and has received research grants from AstraZeneca, Lilly, and Novo Nordisk.
Ole Kleist Jeppesen, Maria De Los Angeles Quiroga Pelaez, and Mette Skalshøi Kjær are employees of Novo Nordisk.
Michael Lincoff declares having received research grants from AbbVie, AstraZeneca, CSL Behring, Eli Lilly and Company, Esperion Therapeutics, and Novartis, paid to his institution; and had served as a consultant for Akebia Therapeutics, Alnylam Pharmaceuticals, Ardelyx, Eli Lilly and Company, FibroGen, GlaxoSmithKline, Intarcia, Medtronic Vascular, Novartis Pharmaceuticals Corporation, Novo Nordisk, Provention Bio, Entity, and ReCor Medical.
Ildiko Lingvay has received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals, Novo Nordisk, Pfizer, and Sanofi US Services; served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals, Biomea, Boehringer Ingelheim, Carmot, Eli Lilly and Company, Intarcia, Intercept Pharmaceuticals, Janssen Global Services, Johnson & Johnson Medical Devices & Diagnostics Group – Latin America, MannKind Corporation, Merck, Novo Nordisk, Pfizer, Sanofi US services, Shionogi, StructureTherapeutics, Target Pharma, Valeritas, and Zealand Pharma; and has received travel expenses from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson Medical Devices & Diagnostics Group – Latin America, Novo Nordisk, Sanofi US services, and Zealand Pharma.
Philip Newsome has received grant/research support from Boehringer Ingelheim and Novo Nordisk; has participated in educational events from Abbott, Echosens, Lilly, and Novo Nordisk; and has received consulting fees from 89Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Madrigal Pharmaceuticals, MSD, Novo Nordisk, Sagimet Biosciences, and Zydus Therapeutics.
Ferruccio Santini has worked as a consultant, participated in studies, or received travel funds from the following companies that are involved with obesity, lipodystrophy, or diabetes: Aegerion/Amryt, BioItalia, Boehringer Ingelheim, Bruno Pharma, Lill, Novo Nordisk, and Pfizer.
Arun J. Sanyal has stock options in Tiziana, Rivus, Durect, NorthSea. He has served as a paid consultant to Intercept, Genfit, Boehringer Ingelhiem, Eli Lilly, Novo Nordisk, Glaxo Smith Kline, Madrigal, Amgen, Genentech, Merck, Zydus, Astra Zeneca, Alnylam, Regeneron, Altimmune, Surrozen, Poxel, Hanmi, Akero Therapeutics, Boston Pharma, 89 Bio, Pliant, Chemomab, Salix, TARGET-MASH, Path AI, Histoindex. His institution receives funding from Avant Sante for consultation with him and has received grants from Novo Nordisk, Hanmi, 89 Bio, Madrigal, Gilead, Akero, Merck, Takeda, Salix, Intercept and Genfit. He receives royalties from Elsevier and Wolter Kluwers.
Steven Kahn has received consulting honoraria from Anii Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Oramed; and stock options from Altpep.
34
Effectiveness of a Pharmacist-Driven Injectable Weight Management Service in a Cardiology Clinic
Kelly Hong, PharmD; Boston Medical Center, Boston, MA
Emily Persson, PharmD; Boston Medical Center, Boston, MA
Kelsey Norman, PharmD, BCCP, BCACP, BCPS; Boston Medical Center, Boston, MA
Kyle Bertram, PharmD, BCACP, CDCES; Boston Medical Center, Boston, MA
Ana Safri, PharmD, MBA, BCACP; Boston Medical Center, Boston, MA
Background:
Heart failure affects approximately 6.7 million individuals, with roughly 40-50% of cases classified as heart failure with preserved ejection fraction (HFpEF) in the United States. Nationally, heart disease is the leading cause of death, which includes another significant group of cardiac conditions related to atherosclerotic cardiovascular disease (ASCVD). Achieving and maintaining a healthy weight may reduce both HFpEF symptoms and ASCVD-related mortality.
Emerging pharmacological options include glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently the most effective pharmacological class of medications for weight management with a favorable cardiovascular safety profile. A more novel mechanism includes an additional glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, which acts synergistically with GLP to promote a healthier metabolic state.
Of these agents, semaglutide (GLP-1 RA) and tirzepatide (GIP/GLP-1 RA) are the most effective, achieving at least 20% weight loss amongst 32% of patients on semaglutide 2.4 mg and 56.7% of patients on tirzepatide 15 mg as demonstrated in the STEP and SURMOUNT studies respectively. Recent studies also demonstrate HFpEF symptom improvement with both agents and reductions in major adverse cardiovascular events with semaglutide.
Purpose:
Between January and December 2023, over 4,000 patients in the cardiology clinic at Boston Medical Center (BMC) had a body mass index (BMI) ≥30kg/m2 with at least one cardiovascular risk factor, including more than 850 patients with heart failure. Given the role of weight management in improving outcomes for patients with HFpEF and ASCVD, there is a clear need for improved access to injectable weight management therapy. Injectable weight management agents have shown proven benefits in both weight and cardiovascular outcomes.
This quality improvement (QI) project aimed to implement a pharmacist-led injectable weight management service to achieve at least 5% weight loss in at least 50% enrolled patients within the cardiology clinic by April 2025. Data collection was extended through August 2025 with continued patient enrollment and management to better assess long-term outcomes.
Methods:
This prospective QI project was conducted at a large, urban, academic medical center, using the Institute for Healthcare Improvement model for Improvement (IHI). The project did not qualify as Human Subjects Research, and iterative changes were tested using Plan-Do-Study-Act (PDSA) cycles.
Outcome metrics included percent weight loss and number of patients initiated on therapy. Process metrics assessed number of completed visits, medication dose adjustments, symptom improvement in patients with heart failure, and time to prior authorization (PA) approval. Balancing metrics included pharmacist access and panel size, number of PA submissions, and rate of adverse effects.
Cardiology providers referred patients to pharmacists, who screened patients via telemedicine appointments. Once medication access and insurance coverage was confirmed, initial in-person visits focused on medication and disease state education, followed by monthly telemedicine follow-ups to monitor medication efficacy and tolerability.
The first PDSA cycle in September 2024 included patients with HFpEF and BMI ≥30kg/m2. The second PDSA cycle in December 2024 expanded to patients with ASCVD and BMI ≥30kg/m2. Additional PDSA cycles in February and March 2025 focused on side effect counseling and workflow optimization. Patients were excluded if they had therapy contraindications or A1C >7% within the last year.
Results:
Between September 1, 2024 and August 30, 2025, 59 patients were started on semaglutide or tirzepatide. Although clinically indicated, 14 did not meet PDSA cycle criteria, 3 were scheduled for their first initial and/or follow-up visit, and 42 completed the initial visit and at least one follow-up pharmacist visit.
The majority of patients were eligible per PDSA cycle 1 (48.9%) as compared to PDSA cycle 2 (33.3%) or both cycles (17.8%). There were limited patients enrolled (n=3) during the first three months, but with implemented workflow changes, numbers increased to n=28 by end of April and to n=45 by end of August. Mean weight loss of 6.76% was observed over 4.29 visits where 61.9% patients achieved at least 5% weight loss. Notably, 8.9% patients were on maximum doses, with 44.4% not yet titrated to maintenance doses.
Overall, therapies were well-tolerated, with one discontinuation due to bradycardia and another due to multiple ED visits for HFpEF exacerbations and GI symptoms. The most common side effects included constipation (24.7%), nausea (19.1%) and diarrhea (9.0%) over a total of 178 completed visits. Despite only one cardiology pharmacy liaison managing PA submissions to ensure medication coverage, cardiology clinic PA submissions were generally steady between 50 – 80 at one-month intervals. However, by end of May 2025, submissions dropped to 10 – 30. This decrease may be attributed to changes in clinic pharmacy liaison staffing and inconsistencies with documentation. Additionally, the mean time from referral placement to PA approval and time from PA initiation to PA approval was 33.1 days and 9.8 days respectively. These numbers are also likely increased over the last few months due to recent staffing changes.
Notably, three patients lost medication access due to insurance and two patients were discharged to alternative weight management clinics within BMC.
Conclusions:
By end of August 2025, the primary outcome of at least 5% weight loss in at least 50% enrolled patients was achieved. Observed barriers included insurance formularies for weight management agents, time to PA approval, and pharmacist scheduling access. As efficiency improves, patient enrollment is planned to expand and mirror on-label indications for patients with comorbid cardiovascular disease. Overall, these results demonstrate favorable patient outcomes with implementing pharmacist-led weight management services in a cardiology clinic, outside of the traditional primary care and weight loss specialty clinics.
Disclosures:
Nothing to disclose by any authors.
35
Impact of semaglutide on liver-related responses in people with metabolic dysfunction-associated steatohepatitis (MASH) with/without type 2 diabetes (T2D): Post hoc analysis of the ESSENCE trial
Elisabetta Bugianesi1, Maria T. Arias-Loste2, Laurent Castera3, Philip Newsome4, Vlad Ratziu5, Mary E. Rinella6, Arun J. Sanyal7, Payal Patel8*, Michael Roden9, on behalf of the ESSENCE study group
Affiliations:
1University of Turin, Turin, Italy,
2Valdecilla Research Institute (IDIVAL), Santander, Spain,
3Hospital Pitié-Salpêtrière, INSERM, Paris, France,
4King’s College Hospital, London, UK,
5Hospital Beaujon, Université Paris Cité, Paris, France,
6University of Chicago, Chicago, IL, USA,
7VCU School of Medicine, Richmond, VA, USA,
8Novo Nordisk Inc, Plainsboro, NJ, USA
9Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
*Presenting author
Background:
ESSENCE is an ongoing phase 3 RCT (NCT04822181) in participants with biopsy-defined MASH and moderate-to-advanced fibrosis (F2 or F3). Part 1 reported positive efficacy on liver histology for the first 800 participants following 72 weeks’ treatment with semaglutide vs placebo.
Purpose:
This post hoc analysis assessed the impact of baseline glycaemia on liver biomarkers and histology.
Methods:
Participants randomised to once-weekly s.c. semaglutide 2.4 mg or placebo were stratified into three groups: normoglycaemia (investigator-assessed non-T2D [NT2D] and baseline [BL] HbA1c ≤5.6%); prediabetes (investigator-assessed NT2D and BL HbA1c 5.7-6.4%); and T2D (investigator-assessed T2D, or investigator-assessed NT2D and BL HbA1c ≥6.5%). Proportions of participants achieving specific liver-related responses at 72 weeks were evaluated, including: a ≥0.5 unit reduction in Enhanced Liver Fibrosis (ELF) score; a ≥30% decrease in liver stiffness measurement by vibration-controlled transient elastography (VCTE LSM); and the two primary histological endpoints (MASH resolution without fibrosis worsening; fibrosis improvement without MASH worsening).
Results:
Participants received semaglutide or placebo (534 and 266, respectively); of these, 132 had normoglycaemia (90 and 42, respectively), 190 prediabetes (128 and 62, respectively), and 478 T2D (316 and 162, respectively) at baseline. Across nearly all glycaemia groups, significantly higher proportions of participants achieved ELF and VCTE LSM responses with semaglutide vs placebo (p=0.009-<0.0001), with greatest effects in the normoglycaemia group on ELF scores and the T2D group on VCTE LSM (Figure). Across glycemia groups, differences in responder proportions tended to favour semaglutide for the two primary histological endpoints, with the greatest effect in the normoglycaemia group (p<0.0001 for both endpoints).
Conclusions:
A benefit of semaglutide treatment on liver-related responses was seen across ELF, VCTE LSM and histological endpoints, regardless of baseline glycaemia.
Disclosures:
Bugianesi advises Boehringer Ingelheim, Eli Lilly, MSD and Novo Nordisk
M.T. Arias-Loste has obtained a grant from Novo Nordisk and has acted in an advisory capacity for MSD and Novo Nordisk and as speaker for Novo Nordisk, Gilead, and Abbie
Castera has served as a consultant for Boehringer Ingelheim, Boston Pharmaceuticals, Echosens, GSK, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet and Siemens Healthineers; and has received lecture fees from AstraZeneca, Echosens, Gilead, Inventiva, Madrigal and Novo Nordisk
Newsome consults, advises, is on the speaker’s bureau for, and received grants from, Novo Nordisk. He consults and advises Boehringer Ingelheim, Bristol Myers Squibb, Gilead, GSK, Intercept, Madrigal, Pfizer, Poxel and Sun Pharma. He is on the speaker’s bureau for AiCME.
Ratziu consults and received grants from Intercept. He consults for Boehringer Ingelheim, Eny, Madrigal, NorthSea, Novo Nordisk, Poxel and Sagimet. He received grants from Gilead.
M.E. Rinella consults for 89bio, Akero, Boehringer Ingelheim, CytoDyn, GSK, HistoIndex, Intercept, Madrigal, NGM Bio, Novo Nordisk, Sagimet and Sonic Incytes. MER has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MER also reports honoraria as a speaker for CME events sponsored by Boehringer Ingelheim, Madrigal and Novo Nordisk.
Sanyal: reports research/grants from Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Fractyl, Gilead, Inventiva, Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, Novartis and Novo Nordisk; consultancy/advisory boards for Albireo, Amgen, AMRA, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Genentech, GENFIT, Gilead, Hemoshear, HistoIndex, Inventiva, Janssen, Eli Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, NGM Bio, NorthSea, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, ProSciento, Regeneron Pharmaceuticals, Inc, Roche, Salix, Sanofi, Siemens, Takeda, Terns and 89Bio; stock for Durect, Exhalenz, GENFIT, Hemoshear, Indalo, Rivus, Sanyal Bio and Tiziana.
P Patel is an employee and shareholder of Novo Nordisk, Inc
M. Roden acted as speaker and/or advisor for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk, Synlab and TARGET RWE and his Center received research grant support from Boehringer Ingelheim and Novo Nordisk for investigator-initiated studies.
36
Semaglutide-treated participants in the phase 3 ESSENCE trial (part 1) have greater concordance of non-invasive test improvements compared with placebo
Mary E. Rinella1, Manal F. Abdelmalek2, Elisabetta Bugianesi3, Laurent Castera4,5, Philip Newsome6,7, Michael Roden8-10, Arun J. Sanyal11, Christin Rogers Marks12*, Vlad Ratziu13, on behalf of the ESSENCE Study Group
Affiliations:
1Division of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA;
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA;
3Department of Medical Sciences, University of Turin, Turin, Italy;
4Université Paris Cité, INSERM UMR1149, Centre de Recherche sur l’Inflammation, Paris, France;
5Service d’Hépatologie, Hôpital Beaujon, Assistance-Publique Hôpitaux de Paris, Clichy, France;
6Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King’s College London and King’s College Hospital, London, United Kingdom;
7College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;
8Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;
9Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany;
10German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany;
11Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, VA, USA;
12Novo Nordisk Inc, Plainsboro, NJ, USA
13Sorbonne Université, Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France
*Presenting author
Background:
The ESSENCE Trial is an ongoing phase randomized phase 3 trial (NCT04822181) in participants with biopsy-defined metabolic dysfunction-associated steatohepatitis and moderate-to-advanced fibrosis (F2 or F3). Part 1 reported positive results for histological and non-invasive test (NIT) endpoints in an interim analysis of the first 800 randomised participants for the first 800 participants following 72 weeks’ treatment with semaglutide vs placebo.
Purpose:
In this secondary analysis of part 1 of the ESSENCE trial, we evaluated treatment response at week 72 through assessment of histology and non-invasive tests (NITs).
Methods:
Of the first 800 randomised participants, those with available measurements for considered NITs and histology results at week 72 (N = 394) were assessed for on-treatment response related to disease activity, defined by having histological resolution of steatohepatitis and no worsening of liver fibrosis, a decrease in alanine transaminase (ALT) levels (≥ 25% from baseline) or improvement in FibroScan-AST (FAST) score (≥ 0.22 points from baseline). For NITs and histology related to fibrosis (N = 494), response was assessed by histological improvement in liver fibrosis and no worsening of steatohepatitis, decrease in liver stiffness measurement by vibration-controlled transient elastography (LSM-VCTE) ≥ 30% from baseline or enhanced liver fibrosis (ELF) score decrease (≥ 0.5 units from baseline).
Results:
Considering measures of disease activity in the semaglutide (n = 269) and placebo (n = 125) arms, 90.3% vs 59.2% met at least one treatment response criteria, respectively. In the semaglutide arm, 45.7% of participants met all response criteria (ALT, FAST and histology) vs 10.4% in the placebo arm. ALT criteria were met by 75.8% of participants in the semaglutide arm vs 37.6% in the placebo arm. Response criteria for any two measures were met and overlapped in 75.1% of participants in the semaglutide arm vs 30.4% in the placebo arm; ALT and FAST responders overlapped in 62.5% in the semaglutide arm vs 20.0% in the placebo arm.
In the semaglutide arm (n = 332), 84.3% met at least one of the treatment response criteria related to fibrosis, compared with 54.9% in the placebo arm (n = 162). Overall, 16.0% of participants in the semaglutide group met all response criteria (ELF, LSM VCTE and histology) vs 5.6% for placebo. LSM-VCTE criteria were met by 53.6% of participants in the semaglutide arm vs 30.9% in the placebo arm. Response criteria for any two measures were met and overlapped in 53.9% of participants in the semaglutide arm vs 19.2% in the placebo arm; ELF and VCTE-LSM responders overlapped in 37.7% in the semaglutide arm vs 10.5% in the placebo arm.
Conclusions:
A higher proportion of participants who received semaglutide met the NIT and histology-based definitions of treatment response compared with placebo. This suggests that more participants may be experiencing improvements in NITs beyond those captured by histology alone. However, the study remains ongoing for clinical outcomes to validate long term clinical benefit.
Disclosures:
MER consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio and Sonic Incytes.
MFA reports research/grants (paid to institution) from 89Bio, Akero, Boehringer Ingelheim, Hanmi, Inventiva, Madrigal; consultancy/advisory boards for 89Bio, Boehringer Ingelheim, Hanmi, Inventiva, Madrigal, and Novo Nordisk; and speaker’s bureau for Clinical Care Options, MedScape, Fishawack Inc. and CLDF.
EB advises Boehringer Ingelheim, Eli Lilly, MSD and Novo Nordisk.
LC has served as a consultant for Boehringer Ingelheim, Boston Pharmaceuticals, Echosens, GSK, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet and Siemens Healthineers; and has received lecture fees from AstraZeneca, Echosens, Gilead, Inventiva, Madrigal and Novo Nordisk.
PN consults, advises, is on the speaker’s bureau for, and received grants from, Novo Nordisk. He consults and advises Boehringer Ingelheim, Bristol Myers Squibb, Gilead, GSK, Intercept, Madrigal, Pfizer, Poxel and Sun Pharma. He is on the speaker’s bureau for AiCME.
CPO has been a consultant or participant in clinical trials for Novo Nordisk, Pfizer, Inventiva, AstraZeneca, Boehringer Ingelheim. GP has received fees for advisory board meetings and lectures from AbbVie, Amgen, AstraZeneca, Elpen, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche, Takeda and Vir Pharmaceuticals and has received research grants from AbbVie and Gilead.
SP acted as speaker and/or advisor for Echosens, MSD, Novo Nordisk, Pfizer, Resalis.
MR acted as speaker and/or advisor for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk, Synlab and TARGET RWE and his Center received research grant support from Boehringer Ingelheim and Novo Nordisk for investigator-initiated studies.
AJS reports research/grants from Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Fractyl, Gilead, Inventiva, Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, Novartis and Novo Nordisk; consultancy/advisory boards for Albireo, Amgen, AMRA, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Genentech, GENFIT, Gilead, Hemoshear, HistoIndex, Inventiva, Janssen, Eli Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, NGM Bio, NorthSea, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, ProSciento, Regeneron Pharmaceuticals, Inc, Roche, Salix, Sanofi, Siemens, Takeda, Terns and 89Bio; stock for Durect, Exhalenz, GENFIT, Hemoshear, Indalo, Rivus, Sanyal Bio and Tiziana.
CRM is an employee of and shareholder of Novo Nordisk, Inc.
VR consults and received grants from Intercept. He consults for Boehringer Ingelheim, Eny, Madrigal, NorthSea, Novo Nordisk, Poxel and Sagimet. He received grants from Gilead.
37
Weight-independent benefits of semaglutide on histology and non-invasive tests in participants with biopsy-defined MASH: Post hoc analysis of the ESSENCE trial part 1
Philip N Newsome1,2, Vlad Ratziu3, Mary E. Rinella4, Michael Roden5-7, Arun J. Sanyal8, Christin Rogers Marks9*, Elisabetta Bugianesi10 on behalf of the ESSENCE study group
Affiliations:
1Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King’s College London, Foundation for Liver Research and King’s College Hospital, London, UK
2College of Medical and Health, University of Birmingham, Birmingham, UK
3Institute of Cardiometabolism and Nutrition, INSERM UMRS 1138 CRC, Hospital Pitié Salpêtrière (ICAN), Sorbonne Université, Paris, France
4Division of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA
5Department of Endocrinology and Diabetology, Medical Faculty and University Hospital of Düsseldorf, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany
6Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
7German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
8Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
9Novo Nordisk Inc, Plainsboro, NJ, USA
10Department of Medical Sciences, University of Turin, Turin, Italy
Background:
The ongoing phase 3 ESSENCE trial (NCT04822181) reported positive results for histological and non-invasive test (NIT) endpoints in an interim analysis of the first 800 randomised participants with biopsy-defined metabolic dysfunction-associated steatohepatitis (MASH) and F2/F3 fibrosis receiving once-weekly subcutaneous semaglutide 2.4 mg vs placebo. Participants receiving semaglutide achieved a mean weight loss of 10.5% vs 2.0% with placebo.
Purpose:
In this post hoc analysis, we assessed the weight dependency of the effects of semaglutide 2.4 mg on study endpoints (NITs and histology) after 72 weeks of treatment, using weight loss-independent and -dependent pathways as covariates.
Methods:
NITs and biopsies were assessed at baseline and week 72. MASH-related NIT responder endpoints were change in alanine aminotransferase (ALT; ≥17-unit reduction) and FibroScan-aspartate aminotransferase (FAST) score (≥0.22 reduction). Fibrosis-related NIT responder endpoints were change in vibration-controlled transient elastography (VCTE) liver stiffness measurement (30% reduction) and Enhanced Liver Fibrosis (ELF) score (≥0.5-unit reduction). Histologic endpoints included resolution of MASH and improvement in fibrosis. All endpoints were assessed using logistic regression at week 72 with treatment as exposure, percentage weight loss from baseline to week 72 as mediator, and baseline type 2 diabetes status, fibrosis stage, and body weight as covariates. The total and weight loss-independent and -dependent effect sizes were calculated as odds ratios (ORs), and missing data were omitted. All data are based on the full analysis set from the on-treatment observation period.
Results:
For MASH-related endpoints, the total effect (OR [95% confidence interval (CI)]) for ALT, FAST score and resolution of MASH without worsening of fibrosis was 4.7 (3.3, 6.6), 6.9 (4.3, 10.9) and 3.9 (2.8, 5.5), respectively. ORs (95% CI) for the weight loss-independent effect were 3.0 (2.0, 4.6), 2.8 (1.7, 4.7) and 2.0 (1.4, 3.0), respectively, and for the weight loss-dependent effect, the ORs (95% CI) were 1.5 (1.2, 2.0), 2.5 (1.8, 3.4) and 1.9 (1.6, 2.4), respectively (Figure 1). Overall, 71.9%, 53.3% and 51.9% of the total effect for ALT, FAST score and resolution of MASH, respectively, were not mediated by weight loss. For the fibrosis-related endpoints, the total effect (OR [95% CI]) for VCTE, ELF score and improvement in fibrosis without worsening of MASH were 3.0 (2.0, 4.4), 4.5 (3.1, 6.4) and 2.1 (1.5, 3.1), respectively. ORs (95% CI) for the weight loss-independent effect were 1.7 (1.1, 2.7), 2.4 (1.6, 3.7) and 1.5 (1.0, 2.4), respectively, and for the weight loss-dependent effect, the ORs (95% CI) were 1.7 (1.4, 2.2), 1.9 (1.5, 2.3) and 1.4 (1.1, 1.8), respectively (Figure 2). This shows that 48.9%, 58.5% and 55.5% of the total effect for VCTE, ELF score and fibrosis improvement, respectively, were not mediated by weight loss.
Conclusions:
Semaglutide 2.4 mg improved MASH-related histological and NIT endpoints and fibrosis-related NIT endpoints through equal contributions of weight loss-independent and -dependent metabolic mechanisms, with effects beyond weight loss.
Disclosures:
Philip N Newsome consults, advises, is on the speaker’s bureau for, and received grants from, Novo Nordisk. He consults and advises Boehringer Ingelheim, Bristol Myers Squibb, Gilead, GSK, Intercept, Madrigal, Pfizer, Poxel and Sun Pharma. He is on the speaker’s bureau for AiCME.
Vlad Ratziu consults and received grants from Intercept. He consults for Boehringer Ingelheim, Eny, Madrigal, NorthSea, Novo Nordisk, Poxel and Sagimet. He received grants from Gilead.
Mary Rinella consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio and Sonic Incytes.
Michael Roden acted as speaker and/or advisor for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk, Synlab and TARGET RWE and his Center received research grant support from Boehringer Ingelheim and Novo Nordisk for investigator-initiated studies.
Arun J. Sanyal reports research/grants from Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Fractyl, Gilead, Inventiva, Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, Novartis and Novo Nordisk; consultancy/advisory boards for Albireo, Amgen, AMRA, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Genentech, GENFIT, Gilead, Hemoshear, HistoIndex, Inventiva, Janssen, Eli Lilly, Madrigal, Malinckrodt, Merck Sharp & Dohme, NGM Bio, NorthSea, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, ProSciento, Regeneron Pharmaceuticals, Inc, Roche, Salix, Sanofi, Siemens, Takeda, Terns and 89Bio; stock for Durect, Exhalenz, GENFIT, Hemoshear, Indalo, Rivus, Sanyal Bio and Tiziana.
Christin Rogers Marks is an employee of and shareholder of Novo Nordisk, Inc.
Elisabetta Bugianesi advises Boehringer Ingelheim, Eli Lilly, MSD and Novo Nordisk.
38
Exploring Food Access, Eating Behaviors, and Metabolic Disease Risk in the Latino Population of Alamance County: A Systems Approach
Katherine Evans, Svetlana Nepocatych, Elizabeth Bailey, affiliated with Elon University.
Background:
The International Diabetes Federation (IDF) defines Metabolic Syndrome (MetS) as an elevated waist circumference and 2 or more of the following: elevated fasting glucose, triglycerides, systolic and/or diastolic blood pressure (SBP/DBP), and low HDL. MetS rates in the US have been steadily increasing, and the Hispanic population consistently shows some of the highest incidence rates in the country. Environmental impacts on MetS have been understudied in Hispanics. Within Alamance County, NC, the area with the highest population of Hispanics experiences an 11-year decreased life expectancy and the highest incidence rates of type 2 diabetes, uninsured persons, and food insecurity as of 2021.
Purpose:
The purpose of this study was to examine which physiological, behavioral and socioeconomic factors are most strongly associated with MetS among Hispanic adults in Alamance County, NC. We hypothesized that factors beyond those identified by IDF, specifically access to healthy food, would influence MetS in this population.
Methods:
A cross-sectional observational study was used. A sample of Hispanic Alamance County residents (n=53) ages 18-65 were recruited from Oct ’24 – Jul ’25. Participants came once to the laboratory while fasting for MetS assessment and questionnaire completion. Translators and translated materials were provided. Questionnaires included demographics (PRAPARE), food access (Food Resource Accessibility Survey), processed foods consumption (sQ-HPF), and a 24-hour dietary recall (ASA-24). Body composition was analyzed by height, weight, and bioelectrical impedance. WC was assessed using WHO protocols. Blood samples were analyzed via Piccolo Plus Lipid panel for glucose, total cholesterol, LDL, HDL, and triglycerides. SBP/DBP was measured using a digital monitor. Serum was analyzed for insulin resistance (IR) by measuring the concentration of insulin in serum through ELISA immunoassay and using the Homeostatic Model for Insulin Resistance (HOMA-IR) to calculate IR values. Any value >1.9 was classified as IR based on the HOMA model. Data was analyzed using unpaired t-test/chi square and logistic regression. Participants were assessed for MetS via the IDF’s guidelines for South Asians, as is recommended for the Hispanic population. Specifically, as those with elevated WC, plus ≥ 2 factors of either elevated fasting glucose, triglycerides, SBP/DBP, or low HDL
Results:
Forty nine percent (26/53) of participants met the IDF criteria for MetS, including 9 males and 17 females. Those with MetS had significantly higher weight (p = 0.01), BMI (p = 0.03), WC (p = 0.008), SBP (p = 0.006), DBP (p = 0.009), fasting glucose (p = 0.003), and IR (p = 0.01) compared to those without MetS. Factors such as healthy eating index, SES, and processed foods consumed were not statistically significant between groups. Three different logistic regressions were run to determine the odds of developing MetS in the presence of different variables. Some of the variables had incomplete datasets either due to ongoing data analysis or a lack of response from participants.
When IR was excluded, transportation and food access were associated with higher odds of developing MetS (OR = 128.9, 95% CI: [1.66->999.9], p = 0.029), and WC (OR = 1.18, 95% CI: [1.03-1.37], p = 0.020) and SBP (OR = 1.23, 95% CI: [1.04-1.45], p = 0.013) were significantly associated with greater odds of MetS.
When transportation was excluded but IR was included, age (OR = 1.22, 95% CI: [1.01-1.46], p = 0.035), IR (OR = 1.70, 95% CI: [1.10-2.62], p = 0.018), and WC (OR = 1.29, 95% CI: 1.07-1.56, p = 0.008) were associated with higher odds of developing MetS, while fat mass percentage was associated with lower odds of developing MetS(OR = 0.81, 95% CI: [0.65-1.01], p = 0.056).
In the model including both IR and transportation, WC (OR = 1.58, 95% CI: [1.06-2.34], p = 0.025), SBP (OR = 1.46, 95% CI: [1.04-2.05], p = 0.030), and transportation and food access (OR >999.9, 95% CI: [2.23->999.9], p = 0.039) were associated with higher odds of developing MetS. IR showed a non-significant association in this model (OR = 5.71, 95% CI: [0.60-54.2], p = 0.13).
Conclusions:
Based on this data, HDL and triglycerides were not reliable measures in determining MetS in this population despite being part of the IDFs criteria for diagnosing MetS in the Hispanic population. In contrast, non-physiological variables such as access to food and transportation, as well as physiological variables not included in the IDFs criteria such as insulin resistance were associated with the development of MetS. This preliminary data suggests that additional variables including social/environmental factors should be considered in the prevention and treatment of MetS in Hispanic communities. Understanding the environmental, behavioral, and socioeconomic factors that influence the development of MetS in different ethnic groups and sub-populations, may allow the design of more targeted interventions and preventative screenings. This can include targeting specific barriers including access to healthy food, transportation, and nutrition education.
Disclosures:
Nothing to disclose by any authors.
39
Utility of using Body Roundness Index (BRI) instead of Body Mass Index (BMI) in clinical practice.
Megha Mallavarapu- AMS Cardiology
Bruce Klugherz MD, AMS Cardiology, Jefferson Abington Hospital.
Background:
Obesity is a global epidemic affecting more than one billion people worldwide and contributing to more than 5 million deaths. It is one of the leading risk factors for mortality. Hence, a better understanding of the obesity-mortality association is crucial for optimizing risk assessment, developing effective anti-obesity strategies, and prioritizing rational allocation of healthcare resources. Traditionally, the Body Mass Index (BMI) is used to assess obesity and has been historically linked to an increased cardiovascular risk. However, it cannot accurately characterize body fat distribution. Recent emerging data suggest that visceral obesity is a stronger predictor of mortality, and a new index, the Body Roundness Index (BRI), offers a more accurate measurement of body fat distribution by incorporating waist circumference alongside height and weight to reflect visceral fat better. BRI was found to be superior to BMI in estimating the risk for various clinical endpoints, including cardiometabolic disease, kidney disease, and cancer. Several longitudinal studies have shown that high BRI was associated with a significantly increased risk of all-cause mortality and cardiovascular disease-specific mortality.
Purpose:
Recent clinical trials reveal a U-shaped relationship between Body Roundness Index (BRI) and mortality, where both low and high values are associated with increased risk. These findings provide compelling evidence for the application of BRI as a non-invasive and easily obtainable screening tool to estimate mortality risk and identify high-risk individuals, a novel concept that could be incorporated into public health practice. Unlike BMI, which is commonly used but limited, BRI incorporates waist circumference to reflect visceral fat and metabolic risk better.
This study aims to quantify the proportion of patients reclassified into higher or lower risk categories when assessed with BRI compared to BMI. Furthermore, it investigates whether an abnormal BRI is more strongly associated with cardiovascular risk than BMI. The findings could provide clinicians with a superior tool for individualized risk stratification, enabling more precise and personalized treatment planning for patients.
Methods:
A dataset of 350 individuals was analyzed, categorizing participants by BMI (normal:
18.5-24.9, overweight: 25-29.9, obese: ≥30) and BRI (normal: ≤6.9, abnormal: >6.9). Descriptive statistics such as means, Chi-square analysis, T-tests, and logistic regression were used. It is a cross-sectional observational study.
This is a retrospective and prospective study of preoperative patients attending the private cardiology group. Several anthropometric measurements including waist circumference, height, and weight were collected for calculation of BMI and BRI.
Body Roundness Index (BRI): Calculated using the formula: 364.2 − 365.5 × √(1 − [waist circumference in centimeters / 2π]2 / [0.5 × height in centimeters]2)
Body Mass Index (BMI): Calculated using the formula: weight (kg) / [height (m)]2.
ASCVD score was calculated using ACC ASCVD calculator.
Clinical Data including: Medical history of hypertension, glucose intolerance/diabetes, lipid disorders, fatty liver, and other relevant conditions obtained via questionnaire. Current medications including Beta blockers, ACE inhibitors, Statins, and other medications like diabetic medications. Pertinent laboratory, demographics, and lifestyle data were also collected.
Approval was obtained from the Institutional Review Board (IRB).
Epi Info, SPSS and Easy Med Stat were used for statistical analysis
Results:
This study demonstrates that relying solely on BMI for metabolic risk assessment may lead to significant misclassification of patients. In patients with a normal BMI, 99% had normal BRI and 1% had abnormal BRI. BMI was not helpful for risk categorizing in this group of patients. In patients who were overweight, 94% had normal BRI and 6% had abnormal BRI. BRI was helpful to risk categorize patients to a higher risk group in about 6% of these patients. This suggests low metabolic risk despite elevated weight-to-height ratios. In patients who were obese, 51% had normal BRI, putting them at a lower risk for metabolic disease. BRI was especially helpful in this group of patients.
In the bivariate analysis, BRI was especially helpful in categorizing patients to a lower risk category in patients who are overweight and obese. In the multivariate analysis, abnormal BRI was more associated with obesity in women than in men. High BRI was associated with slightly increased risk of diabetes and mental health disorders. In the rest of the variables collected, there was no significant association with abnormal BRI.
There was a secondary clinical dataset of 128 adults (67 women, 61 men; ages 40-79). After cleaning and standardizing the variables, analyses focused on how BRI and BMI related ASCVD risk and how well each measure identified patients at or above the 7.5% ASCVD threshold. Across the full sample, BMI and BRI were very similar to one another and moved together closely. Neither measure showed a meaningful relationship with ASCVD risk when treated as continuous variables. The share of patients above the 7.5% ASCVD threshold was also similar across BMI categories (<25, 25-30, >30). Results were the same in women when using BRI categories. In men, however, higher BRI categories were linked with a larger share of patients above the 7.5% threshold (72.0%, 96.3%, and 100.0% across increasing BRI groups). This pattern should be read with caution because some groups were small.
Conclusions:
The significant discordance between BMI and BRI classifications observed in our study has important clinical implications, particularly for patients who may be subjected to unnecessary interventions based on BMI-derived risk assessments alone. For patients classified as overweight or obese by BMI but showing normal BRI values, clinicians might reasonably adopt less aggressive intervention strategies, focusing instead on maintaining healthy lifestyle behaviors. When examining how well each measure separated high- from low-risk patients, curves of sensitivity vs. false-positive rate showed little separation overall and in women. In men, BRI separated the groups better than BMI and performed in a range that suggested useful discrimination, while BMI did not. Together, these findings indicated that BRI did not outperform BMI in the full sample, but it showed an advantage among men. Age was the clearest factor in the data. Average ASCVD risk rose steadily from the 40s to the 70s. In contrast, average BMI and BRI were fairly stable across decades of life. Overall, the results suggested that body size and shape measured by BMI and BRI were not strong indicators of ASCVD risk in this cohort as a whole, although BRI may be more informative for men.
Disclosures:
Nothing to disclose by any authors.
40
SGLT-2 Inhibitor administration post percutaneous coronary intervention: a systematic review
Shreya Avilala (1), Koray N Potel, MB BCh BAO (2), Annie Shao, PhD (2), Rosemary F Kelly, MD (2)
1: University of Minnesota Medical School, 2: University of Minnesota Department of Surgery
Background:
Myocardial infarction (MI) remains the leading cause of death in the United States. Despite improved survival through early percutaneous coronary intervention (PCI), development of post-infarct heart failure remains a challenge and novel ways to promote myocardial recovery are needed. Sodium Glucose Co-transporter 2 (SGLT2) inhibitors are a novel class of antidiabetic medications which prevent the reabsorption of glucose in the proximal tubule of the kidneys. While initially developed to treat hyperglycemia, many cardiorenal benefits have been observed with the use of this medication. Regular use of SGLT2 inhibitors results in improved blood pressure control due to natriuresis in addition to reduction of albuminuria due to a blockade of the renin-angiotensin-aldosterone system. Furthermore, SGLT2 inhibitors have been shown to prevent hospitalization and cardiovascular death in patients with heart failure.
The cardiac effect of SGLT2 inhibitors have been hypothesized to be both direct and indirect. Direct effects include reduction in sodium/hydrogen exchanger and calmodulin-dependent protein kinase II activity, as well as regulation of autophagy and the inflammasome. Indirect effects may be exerted among other things through glucose availability and improved renal function. Given these findings, several studies have investigated the potential benefits of SGLT2 inhibitors in post-infarct cardiac recovery.
Purpose:
The purpose of this study was to systematically review the available literature and identify studies which investigated the use of SGLT2 inhibitors in patients who had recently undergone PCI post-MI. We aimed to summarize the effects of SGLT2 inhibitors on soluble biomarkers of myocardial function, metabolism as well as inflammation and determine whether current evidence supports the use of SGLT2 inhibitors as adjunctive treatment following PCI in patients with or without diabetes mellitus.
Methods:
Two databases, Pubmed and Embase, were screened for human randomized clinical trials and observational studies from 08/2015 to 08/2025 in adults who underwent PCI and were treated with an SGLT2 inhibitor. The following search terms were used: “(sglt2 inhibitors) AND (percutaneous coronary intervention)”. Studies where soluble cardiac, metabolic or inflammatory biomarkers were either the primary or secondary endpoint were included. Results were summarized and synthesized to determine overall trends.
Results:
Eight eligible studies were identified and further analyzed. The main endpoints assessed were brain natriuretic peptide (BNP) and inflammatory markers, including c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6). BNP was an endpoint in three of the included studies. When compared to placebo, patients who received an SGLT-2 inhibitor had significantly lower BNP levels at three, six, and twelve months post-PCI. Six studies included inflammatory markers as endpoints. CRP was significantly lower at discharge and up to twelve months post-PCI in patients treated with SGLT-2 inhibitors. Similarly, serum levels of TNF-a and IL-6 were significantly reduced in SGLT2 inhibitor cohorts at six and twelve months following PCI. Four studies included non-diabetic patients, which concluded diabetes status did not seem to affect whether SGLT2 inhibitor treatment resulted in an improvement in biomarker levels post-PCI.
Conclusions:
Our systematic review of the literature indicates that treatment with SGLT2 inhibitors results in a significant reduction in cardiac and inflammatory biomarkers following PCI. Hence, SGLT2 inhibitors might promote myocardial recovery following MI. Since results were also reproduced in studies including non-diabetic patients, these benefits might apply to all patients undergoing PCI irrespective of diabetic comorbidities. Future studies are needed to guide clinical decision-making and to better understand the mechanisms underlying the cardioprotective effects of SGLT2 inhibitors.
Disclosures:
Nothing to disclose by any authors.
41
Association of Exposure to Multiple Chemical Contaminants with Diabetes Mellitus in Chinese Adults: Mixture Associations and Metabolic Mediation
Denghui Meng, PhD
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Xuzhi Wan, PhD
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Lange Zhang, MPH
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Yimei Tian, PhD
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Wei Jia, PhD
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Xiaoran Song, MSc
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Pan Zhuang, PhD
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Jingjing Jiao, PhD
Department of Endocrinology, The Second Affiliated Hospital; Department of Nutrition, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China
Yu Zhang, PhD (Corresponding Author)
Email: y_zhang@zju.edu.cn
Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University School of Medicine; Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China
Background:
Diabetes mellitus (DM) is a global health challenge with a rapidly increasing prevalence, imposing a significant burden on individuals and healthcare systems. Environmental and lifestyle factors are recognized as key contributors to the development of type 2 diabetes. Among these, chemical contaminants found in thermally processed foods and the environment, such as acrylamide, 3-monochloropropane-1,2-diol (3-MCPD), glycidol, and thiocyanate, have garnered attention for their potential to disrupt metabolic processes. Acrylamide is considered a probable human carcinogen and has shown diabetogenic effects in some studies. Similarly, 3-MCPD and glycidol have been linked to metabolic syndrome, while thiocyanate’s role in metabolic health has yielded conflicting results. Although individual associations have been explored, humans are ubiquitously exposed to a mixture of these contaminants. The joint health effects of co-exposure remain largely unclear, representing a critical knowledge gap in understanding real-world exposure risks and their impact on DM.
Purpose:
This study aimed to investigate the associations between exposure to a mixture of four common chemical contaminants-acrylamide, 3-MCPD, glycidol, and thiocyanate-and the prevalence of diabetes mellitus (DM) in a Chinese adult population. We hypothesized that combined exposure to these contaminants would be positively associated with an increased prevalence of DM. The secondary objectives were to identify the key chemical contributors to the overall mixture effect and to explore potential non-linear dose-response relationships. Furthermore, we aimed to uncover potential biological mechanisms by examining whether the observed associations are mediated by alterations in plasma metabolite profiles. This research seeks to provide novel insights into the complex interplay between mixed chemical exposures, metabolic alterations, and DM prevalence.
Methods:
This cross-sectional analysis utilized data from 1,744 adults aged 40-75 years participating in the Precision Nutrition and Food Safety (PNFS) study in Zhejiang, China. Urinary biomarkers for acrylamide (AAMA, AAMA-sul, GAMA, iso-GAMA), 3-MCPD and glycidol (DHPMA), and thiocyanate were quantified using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). DM was diagnosed based on American Diabetes Association criteria, including self-reported diagnosis, use of hypoglycemic medication, fasting plasma glucose ≥7.0 mmol/L, or HbA1c≥6.5%. Advanced statistical models, including Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection and quantile g-computation, were employed to assess the joint and individual effects of the contaminant mixture on DM prevalence, adjusting for multiple covariates. Untargeted metabolomics analysis was performed on plasma from a subset of 342 participants (110 DM cases, 232 controls) to identify potential metabolic mediators, which were subsequently evaluated using causal mediation analysis.
Results:
Among the 1,744 participants, 260 (14.9%) were diagnosed with DM. Individuals with DM had significantly higher urinary concentrations of iso-GAMA (a biomarker of acrylamide), DHPMA (a biomarker of 3-MCPD and glycidol), and thiocyanate compared to non-DM participants. In fully adjusted logistic regression models, each unit increase in log-transformed urinary iso-GAMA and thiocyanate was associated with a 49% (OR: 1.49, 95% CI: 1.17, 1.91) and 44% (OR: 1.44, 95% CI: 1.20, 1.74) increased prevalence of DM, respectively.
Both BKMR and quantile g-computation analyses demonstrated a significant positive joint association between the contaminant mixture and DM prevalence. The joint effect became significant when all biomarkers were at or above their 55th percentile. BKMR analysis with hierarchical variable selection identified thiocyanate as the key contributor to this joint effect (groupPIP = 0.948). Furthermore, the relationship between thiocyanate exposure and DM prevalence was observed to be nonlinear.
Metabolomics analysis identified 11 plasma metabolites that were significantly associated with both DM status and urinary thiocyanate levels. Causal mediation analysis revealed that six of these metabolites significantly mediated the association between thiocyanate and DM. Acrylic acid and glucose were the most important mediators, accounting for 36.19% (P for mediation = 0.022) and 35.22% (P for mediation = 0.010) of the total association, respectively.
Conclusions:
This study provides compelling evidence of a positive joint association between co-exposure to a mixture of common chemical contaminants and the prevalence of DM in Chinese adults, with thiocyanate identified as a key contributor exhibiting a nonlinear relationship. Our findings underscore the public health importance of assessing real-world mixed exposures, as current single-chemical safety standards may not be sufficiently protective. The identification of acrylic acid and glucose as significant mediators offers novel mechanistic insights, suggesting that thiocyanate may influence DM risk by disrupting glycemic control and potentially pro-inflammatory pathways.
For future research, longitudinal studies are needed to establish causality and clarify the temporal relationship between exposure and DM development. Validating these findings in diverse populations with different dietary patterns is crucial for generalizability. Further experimental and mechanistic studies are warranted to fully elucidate the biological pathways, particularly the role of acrylic acid, and to investigate potential gene-environment interactions that may modify individual susceptibility. These results suggest that strategies to reduce exposure to certain contaminants could be relevant for diabetes prevention.
Disclosures:
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was financially supported by the National Key Research and Development Program of China (grant no. 2024YFF1106700).
42
Association of Family History of Cardiovascular Disease with Cardiometabolic Risk Factors in Young Adults
Fatima Mezhal (corresponding author)1, Amar Ahmad1, Luai A. Ahmed2, Abdishakur Abdulle1
1 New York University Abu Dhabi, UAE
2 United Arab Emirates University, UAE
Background:
A family history of cardiovascular disease (CVD) plays a crucial role in determining an individual’s predisposition to cardiometabolic conditions, with risk intensifying as the number of affected family members increases. This relationship reflects a combination of genetic, environmental, and lifestyle influences.
Purpose:
This study investigates the association between family history of CVD and key cardiometabolic risk factors (CRFs)—including hypertension, dysglycemia, dyslipidemia, and obesity—while also assessing the impact of having multiple affected first-degree relatives.
Methods:
This cross-sectional analysis utilized baseline data from the UAE Healthy Future Study (UAEHFS), which included 5,058 participants under 40 years old. Self-reported family history of heart disease, stroke, hypertension, type 2 diabetes (T2D), high cholesterol, and obesity in parents and siblings was collected through a structured questionnaire. CRFs were determined based on anthropometric measurements, biochemical assessments, and self-reported medical conditions. Multivariate regression models were applied to evaluate associations between varying degrees of family history and the presence of CRFs.
Results:
A substantial proportion (58%) of participants reported having a family history of CVD or related risk factors, with T2D (39.8%) and hypertension (35%) being the most frequently reported family history. The prevalence of all CRFs was significantly higher among individuals with a positive family history compared to those without (P < 0.001). Furthermore, a dose-response relationship was observed, where an increasing number of affected parents or siblings corresponded with a greater likelihood of developing CRFs. The strongest associations were found in individuals in the combined parental-and-sibling history of disease, where the odds increased to 2.36 (95% CI: 1.68–3.32) for hypertension, 2.59 (95% CI: 1.86–3.60) for dysglycemia, 1.90 (95% CI: 1.29–2.91) for dyslipidemia, and 3.79 (95% CI: 2.83–5.06) for obesity.
Conclusions:
This study underscores the significant impact of family history on cardiometabolic health among young Emirati adults. The findings highlight the increased prevalence of CRFs among those with a family history of CVD-related conditions, with a stronger risk observed among individuals with multiple affected relatives. Given the strong familial influence, incorporating family history into early screening and personalized prevention strategies could be instrumental in reducing future cardiometabolic disease burden.
Disclosures:
Nothing to disclose by any authors.
43
Elevated Lipoprotein(a) Is Associated With Myocardial Infarction and Extent of Myocardial Infarct, Particularly in Premature Atherosclerosis
Szilard Voros1,*, Wess Boatwright2, Denise P. Yates3, David S. Watson4, Michael R. Barnes1, Harpreet S. Bhatia5, Sarah J. Rinehart6, Fatima Rodriguez7, Zahi Fayad8, Thomas Dayspring9
1G3 Therapeutics, Midlothian, VA, USA; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis, Biomedical Research, Cambridge, MA, USA; 4King’s College London, London, UK; 5University of California San Diego, San Diego, CA, USA; 6Charleston Area Medical Center, Charleston, WV, USA; 7Stanford University School of Medicine, Stanford, CA, USA; 8BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 9Global Institute for Research, LLC, Richmond, VA, USA
Background:
Elevated lipoprotein(a) [Lp(a)] is an independent, genetic, causal risk factor for cardiovascular disease that drives the progression of premature cardiovascular events. Previous studies have shown that greater infarct size is associated with worse clinical outcomes compared with smaller infarct size and may be a negative prognostic factor. Although individuals with elevated (≥50 mg/dL) and intermediate (30–50 mg/dL) Lp(a) levels are known to have an increased risk of myocardial infarction, the impact of Lp(a) on infarct size has not been fully elucidated. The Genetic Loci and the Burden of Atherosclerotic Lesions (GLOBAL) study utilized multi omics analyses and deep phenotyping of coronary atherosclerosis via coronary computed tomography angiography (CCTA) to evaluate the pathology of atherosclerotic cardiovascular disease (ASCVD). The ongoing Lp(a) subanalysis of the GLOBAL study hypothesizes that Lp(a) driven ASCVD represents a unique, high-risk phenotype compared with non–Lp(a) driven ASCVD.
Purpose:
To evaluate whether intermediate (30–50 mg/dL) or elevated Lp(a) (≥50 mg/dL) is associated with the presence and extent of myocardial infarct (MI). We also aim to determine whether elevated Lp(a) is an independent, causal factor in the extent of MI in premature ASCVD (defined as <55 and <65 years of age in men and women, respectively).
Methods:
A TriNetX query was conducted using EHR data within the US Collaborative Network including 45 HCOs. Patients aged 18 to 75 years with ICD or CPT codes for diagnosis, procedure, or evaluation related to heart transplant (index event) between January 1, 2015 and December 31, 2024 were included. All study patients were prescribed an immunosuppressant (excluding cyclosporine) within the first year after the index event (IE). Patients prescribed GLP-1 agonists during the study period were excluded. Cohorts were distinguished based on treatment with high-intensity (HI) vs low- and moderate-intensity (LMI) statins, and patients must have been prescribed for at least three instances within the first year after IE. Propensity score matching by baseline demographics (age at IE, race, sex), comorbidities (hypertension, dyslipidemia, T2DM, PVD, nicotine dependence), and characteristics (BMI, HbA1c, creatinine) yielded 797 subjects within each group. Outcomes were analyzed from 30 days to 10 years following IE. The primary outcome was combined 5-Point MACE (angina/myocardial infarction, stroke, cardiac arrest, heart failure, invasive cardiac procedure). Secondary outcomes included all-cause mortality, cardiovascular disease, ischemic heart disease, cerebrovascular disease, heart failure, invasive cardiac procedures, and myalgia. Patients with outcomes prior to the time window were excluded from risk calculations.
Results:
In total, 800 patients were included from the GLOBAL study; 74.8% were male, and the median age (range) was 61.0 (55.0–68.0) and 57.0 (52.0–65.0) years for cases (n=400) and controls (n=400), respectively. Median Lp(a) mass (Q2) was 11.1 mg/dL; Q1, Q3 and IQR were 5.3, 46.4 and 41.1 mg/dL, respectively. Median Lp(a) in Q1 through Q4 was 2.9, 7.9, 20.3, and 76.2 mg/dL, respectively. Median Lp(a) mass levels were significantly higher in cases vs controls (14.5 vs 9.8 mg/dL, P<0.001) and in patients with MI detectable by cardiac computed tomography vs those without (19.6 vs 10.5 mg/dL, P=0.015). The proportion of patients with MI detectable by cardiac computed tomography was significantly higher for patients with Lp(a) levels ≥30 vs <30 mg/dL (23.1% vs 16.0%, P=0.011) and ≥50 vs <50 mg/dL (23.6% vs 16.6%, P=0.021). Similar differences were observed for patients with a clinical history of myocardial infarction at ≥30 vs <30 mg/dL (60.2% vs 45.4%, P<0.001) and at ≥50 vs <50 mg/dL (63.4% vs 45.8%, P<0.001). Small isoform Lp(a), but not large isoform Lp(a), was significantly higher in patients with a clinical history of myocardial infarction vs those without (8.45 vs 4.5 nmol/L, P<0.001). Similarly, small isoform Lp(a) was significantly higher in patients with the presence of MI detectable by cardiac computed tomography vs in patients without detectable MI (9.43 vs 5.9 nmol/L, P=0.038). When assessed across the entire range of apoB, Lp(a) was identified as a potential causal factor driving the extent of MI in patients with premature ASCVD (rho 0.7), but not in patients with non premature ASCVD (rho −0.03). In patients with premature ASCVD, there was a sharp increase in the number of myocardial segments involved when Lp(a) levels exceeded 70 mg/dL.
Conclusions:
In this subanalysis of patients from the GLOBAL clinical study, intermediate and elevated Lp(a) levels were significantly associated with the presence of MI identified by cardiac computed tomography and a history of myocardial infarction. In addition, elevated Lp(a) was found to be a potential independent, causal factor driving the extent of MI in patients with premature ASCVD, especially when Lp(a) levels were greater than 70 mg/dL.
Funding source:
This study is sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Medical writing support was provided by Jess Loraine, PhD, of BOLDSCIENCE Ltd., and was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, in accordance with GPP 2022 guidelines. The authors had full control of the content and made the final decision on all aspects of this publication.
Disclosures:
Szilard Voros and Michael R. Barnes are employees of G3 Therapeutics. Wess Boatwright and Denise P. Yates are employees of Novartis. Harpreet S. Bhatia has received consultancy fees from Novartis, Kaneka Corporation, Arrowhead Pharmaceuticals, New Amsterdam, and Abbott. David S. Watson, Sarah J. Rinehart, and Zahi Fayad have nothing to disclose. Fatima Rodriguez has received consulting fees from Novartis, Novo Nordisk, Esperion Therapeutics, Movano Health, Kento Health, Edwards, Arrowhead Pharmaceuticals, Heartflow, iRhythm, Amgen, and Cleerly Health. Thomas Dayspring has received consulting fees from New Amsterdam.
44
Clinical and Demographic Profile of People Living with Cardiovascular diseases and HIV Comorbidities in Abuja, Nigeria
Elonna M Obak1; Sussan Israel-Isah2; Olanrewaju Eniade3; Ezekiel Ukwenga 4 ; Olasunkanmi Yusuff Akinkunmi2;; Evaezi Okpokoro1
1 Health Improvement Scotland, National Health Service, United Kingdom, 2 Institute of Human Virology Nigeria, 3 The International Foundation Against Infectious Diseases in Nigeria (IFAIN), 4 NHS University Hospitals of Liverpool Group
Background:
Cardiovascular diseases (CVDs) are the leading cause of death globally, responsible for an estimated 18 million deaths annually. Viral infections and CVDs share a bidirectional relationship: viral infection can increase CVD risk, while individuals with CVD may be more vulnerable to viral infections. People living with HIV (PLHIV) face particularly elevated risks of stroke, and heart failure. Though the life expectancy of PLHIV seem to have improved in Nigeria as result of effective antiretroviral therapy the burden of diseases of aging including CVDs is most likely to be increased among people living with HIV. Understanding of this heightened HIV-associated cardiovascular risk have evolved over the past 2 decade with much of the evidence originating from Europe and North America, while research from sub-Saharan Africa remains limited. To address this gap, we investigated the prevalence and clinical characteristics of HIV among patients with CVD in Abuja, Nigeria.
Purpose:
This study emerged from a larger investigation into cardiovascular diseases (CVDs) and behavioral risk factors, including harmful alcohol use, in Abuja, Nigeria. Specifically, it examined the relationship between drinking status and the occurrence of CVDs among residents. As part of the data collection, participants were also asked to report any additional health conditions alongside their CVD diagnosis. Interestingly, a significant number of respondents reported living with HIV, far exceeding reports of other comorbidities. In Nigeria, where clinical efforts largely focus on achieving undetectable viral loads among people living with HIV (PLHIV) and ensuring widespread access to antiretroviral therapy, little attention is given to the potential cardiovascular risks associated with HIV and its treatment. This finding prompts an important question: could this gap in care contribute to the disproportionately high burden of non-communicable diseases, particularly CVDs, in low- and middle-income countries? Addressing this issue may be critical in reducing the global burden of CVDs, the leading cause of death worldwide.
Methods:
This analysis was conducted as part of a larger project titled “Prevalence of Alcohol Misuse in Patients Diagnosed with Cardiovascular Diseases in Abuja, Nigeria.” In this abstract, we examined the prevalence of HIV and its association with key demographic and socioeconomic factors among hospital patients who have been diagnosed with cardiovascular disease. A total of 596 participants were included in the analysis. Demographic characteristics such as age, gender, education, marital status, employment, ethnicity, and alcohol use were assessed using structured questionnaires. HIV status (positive vs. negative) was the primary outcome variable. Descriptive statistics were generated to summarize demographic characteristics, while chi-square (χ²) tests were used to examine bivariate associations between HIV status and categorical covariates. Results were reported as frequencies and percentages, with p-values. All statistical analyses were conducted using Stata MP version 17 (StataCorp, College Station, TX, USA). A significance threshold of p < .05 was used to determine statistical significance.
Results:
The overall prevalence of HIV was 8.2% (49/596). Of the 49, 53.1% were female. Most were aged 35–49 years (55.1%), followed by 50–59 years (28.6%) and ≥60 years (16.3%). Also, 57.1% had primary/secondary education, 38.8% tertiary, and 4.1% none. The majority were married (77.6%) and employed (81.6%). In addition, 26.5% were Hausa, 12.2% Yoruba, 8.2% Igbo, and 53.1% were categorized as “Others,” which included Akwa-Ibom, Bassa, Ebira, Edo, Gbagi, Ibibio, Idoma, Jos, Jukun, Kaduna, Kanuri, Kataf, Plateau, and Tiv. About 71% screened positive for potential alcohol abuse. Cardiovascular conditions reported included hypertension (91.8%), heart failure (14.3%), abnormal heart rhythms (8.2%), coronary artery disease (8.2%), deep vein thrombosis/pulmonary embolism (8.2%), heart attack (6.1%), congenital/valvular/pericardial/rheumatic disease (≤2%), and stroke (4.1%). Other diagnoses such as cardiomyopathy (4.1%), aortic disease (12.2%), and large heart (2.0%) were also noted. Overall, 20.4% reported heart disease and 95.9% vascular disease. Nearly half (46.9%) had a family history of cardiovascular disease. Based on BMI, 20.4% were normal, 49.0% overweight, and 30.6% obese. Also, 30.6% had low intake of quality diet, while 69.4% had moderate intake of quality diet. Among participants with HIV, 28.6% reported experiencing a heart attack or stroke in the past three months and 46.9% reported experiencing heart pain in the past three months. In addition, 2.2% very high (>190 mg/dL) LDL, 2.2% high (160–189 mg/dL) and 31.1% had borderline high (130–159 mg/dL) LDL. For HDL, 60.0% had low (<40 mg/dL), 8.9% acceptable (40–60 mg/dL), and 31.1% desirable (>60 mg/dL).
Conclusions:
This study observed an HIV prevalence of 8.2% among patients diagnosed with cardiovascular disease (CVD) in Abuja, Nigeria, which is substantially higher than estimates in the general population. The demographic profile showed that most affected individuals were middle-aged, married, and employed, with alcohol misuse, overweight/obesity, and suboptimal lipid and dietary profiles being common. Cardiovascular diagnoses were dominated by hypertension and vascular disease, with a notable proportion also reporting heart failure and other CVD conditions. These findings highlight the clustering of lifestyle, clinical, and sociodemographic risk factors among people living with HIV and CVD. While the descriptive nature of this study precludes causal inference, it underscores the need for closer attention to cardiovascular health in the management of people living with HIV in Nigeria.
Keywords: HIV; cardiovascular disease; comorbidity; Nigeria
Disclosures:
Nothing to disclose by any authors.
45
Prevalence of metabolic-dysfunction associated steatotic liver disease (MASLD) and metabolic-dysfunction associated steatohepatitis (MASH) in subjects with severe hypertriglyceridemia (SHTG): Baseline data from the pegozafermin ENTRUST Phase 3 SHTG Trial
Deepak L. Bhatt, MD, MPH, MBA, Daniel Gaudet, MD, PhD, Kevin C. Maki, PhD, Maciej Banach, MD, PhD, Guillermo Umpierrez, MD, Germaine D. Agollah, PhD, Cynthia L. Hartsfield, PhD, Teresa Parli, MD, Kausik K. Ray, MD, Harold Bays, MD
Background:
Severe hypertriglyceridemia (SHTG), defined as TG ≥500 mg/dL, impacts roughly 3 million adults with a higher prevalence observed in individuals with metabolic co-morbidities such as obesity, diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD).1-2 To date, the estimated prevalence of MASLD in patients with SHTG is approximately 67% based on claims data, which may be subject to limitations bias.3 We evaluated a subset of SHTG subjects for the presence of hepatic steatosis, a marker of MASLD, in a Phase 2 clinical trial (ENTRIGUE) studying pegozafermin (PGZ), a long-acting glycoPEGylated analog of human fibroblast growth factor 21 (FGF21), for the treatment of SHTG.4 Those data demonstrated that 100% of subjects who underwent assessment by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for fatty liver at baseline had ≥5% hepatic steatosis.5 However, it remains unclear whether these patients had simple steatosis or more advanced disease such as metabolic dysfunction-associated steatohepatitis (MASH) which can include fibrosis. Currently, PGZ is being studied in a Phase 3 randomized controlled trial in SHTG subjects (ENTRUST trial) in which a large subset of patients had baseline assessments for both liver fat and stiffness.
Purpose:
To assess the blinded baseline prevalence of MASLD and MASH in a subset of SHTG patients participating in the ENTRUST trial, using hepatic steatosis ≥5% and liver stiffness measurements ≥7.5 kPa indicative of fatty liver and fibrosis ≥F2, respectively.
Methods:
ENTRUST is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pegozafermin in subjects with SHTG. The study duration is 52 weeks. A subset of randomized SHTG subjects was assessed for hepatic steatosis by MRI-PDFF and liver stiffness by vibration-controlled transient elastography (VCTE) at sites where imaging was available. Results are summarized by descriptive statistics.
Results:
Of the 368 randomized subjects, blinded MRI-PDFF data were available for 168 (based on a cut-off date of August 1, 2025). Baseline characteristics demonstrated a mean age of 54 (SD: 10.9), 75% male, a mean BMI of 31 kg/m2(SD: 4.8) and 57% with a history of type 2 diabetes. The median baseline TG level was 750 mg/dL (IQR: 564,1059; 8.5 mmol/L), and 149/168 (89%) patients had hepatic steatosis ≥5%. The mean baseline hepatic fat fraction was 15.7% (SD: 9.0%), which is similar to baseline values typically seen in trials enrolling MASH patients. The mean liver stiffness was 7.9 kPa (SD: 7.3) with 45/120 (37.5%) having values ≥7.5 kPA suggesting the presence of significant fibrosis (F2).
Conclusions:
The high prevalence of clinically significant hepatic steatosis in this clinical trial indicates the association between SHTG and MASLD is likely underestimated when using claims data. The inclusion of liver stiffness assessment in this study also highlights that many patients with SHTG are at risk for not only simple steatosis, but MASH with fibrosis, reinforcing the urgency to evaluate liver health in these patients. PGZ, currently in Phase 3 for both SHTG and MASH, has previously established broad metabolic benefits, including improvements in liver fibrosis, hepatic steatosis, circulating TGs, and glycemic control, demonstrating its potential to treat both disease states. These preliminary baseline findings in the ENTRUST trial, along with previous data from ENTRIGUE, suggest that routine assessment of liver fat and stiffness may be warranted in SHTG patients.
- Circulation Volume 140, Number Suppl_1: Abstract 14745
- J Clin Lipidology 2023;17(6):777-787
- JACC Adv. 2024; May, 3 (5). https://doi.org/10.1016/j.jacadv.2024.100932
- Nat Med 2023; 29:1782-1792
- Proceedings 2022;80(1):6 Keynote poster abstract 2.4
Disclosures:
Deepak L Bhatt: Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai
Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);
Consultant: 89bio, Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene;
Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial);
Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee);
Other: Clinical Cardiology (Deputy Editor);
Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent);
Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio;
Royalties: Elsevier (Editor, Braunwald’s Heart Disease);
Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions;
Trustee: American College of Cardiology;
Unfunded Research: FlowCo.
Daniel Gaudet: ECOGENE-21 and Dept of Medicine, Université de Montréal, Chicoutimi, Canada
Consultant: 89Bio, Amgen, Arrowhead, Astra Zeneca, Chiesi, CRISPR Therapeutics, Eli Lilly, Esperion, Ionis, Merck, New Amsterdam, NovoNordisk, Regeneron, Rona Therapeutics, Ultragenyx, Verve Therapeutics.
Research grants: ECOGENE-21, an academic non-profit research organization.
Kevin C Maki: Midwest Biomedical Research
Consultant: Amgen, Beren Therapeutics, Eli Lilly & Co., Matinas Biopharma, 89Bio, NorthSea Therapeutics, Jason Pharmaceuticals
Research Grants: Beren Therapeutics, Eli Lilly & Co., Novo Nordisk, Jason Pharmaceuticals
Maciej Banach: Department of Preventive Cardiology and Lipidology, Medical University of Lodz
Consultant: 89bio, Adamed, Amgen, Daiichi Sankyo, Lilly, MSD, New Amsterdam, Novartis, Novo-Nordisk, Sanofi, Teva
Speaker: Amgen, Adamed, Daiichi Sankyo, KRKA, MSD, Polpharma, Mylan/Viatris, Novartis, Novo-Nordisk, Pfizer, Sanofi, Teva, Zentiva;
Grants: Amgen, Daiichi Sankyo, Viatris, Sanofi, and Teva.
Guillermo Umpierrez: Emory University School of Medicine
Consultant: 89bio, Dexcom, Corcept, Glucotrack, and Glycare
Research support: Bayer, Corcept, Abbott, Glucotrack, and Dexcom. Research grants from the National Institutes of Health (NIH/NATS UL 3UL1TR002378-05S2) through the Clinical and Translational Science Award program, and from the NIH and the National Center for Research Resources (NIH/NIDDK 2P30DK111024-06)
Kausik K Ray: Department of Primary Care and Public Health, School of Public Health, Imperial College London
Consultant: Novartis, Daiichi Sankyo, Kowa, Esperion, 89bio, Novo Nordisk, MSD, Lilly, Silence Therapeutics, AZ, New Amsterdam Pharma, Bayer, Beren Therapeutics, CLEERLY, EMENDOBIO, SCRIBE, CRISPR, VAXXINITY, Amarin, Regeneron, Ultragenix
Speaker: (CME and non-CME): Novartis, BI, AZ, Novo Nordisk, Viatris, Amarin, Sanofi, Amgen, Esperion, Daiichi Sankyo, Macleod Pharma
Stock options: New Amsterdam Pharma, SCRIBE and PEMI31
Harold Bays: Louisville Metabolic and Atherosclerosis Research Center
Consultant: 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Eva Pharma, Kiniksa, HighTide, Lilly, Nestle, Novo Nordisk, Regeneron, Rivus, Veru, Zomagen, ZyVersa.
Research Support: 89Bio, Abbvie, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, AstraZeneca, Bioage, Biohaven, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, GlaxoSmithKline, Graviton, HighTide, Home Access, Horizon, Ionis, Kallyope, LG-Chem, Marea, Madrigal, Marea, Merck, Mineralys, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, Tern, TIMI, Veru, Viking, Vivus, Zomagen.
Germaine D Agollah, Cynthia L Hartsfield and Teresa Parli: 89bio Inc
89bio employee and stockholder
