Poster Abstracts

CardioMetabolic Medicine: A Proposed Curriculum for an Emerging Field to Provide Clinical and Research Training in Prevention and Treatment of Cardiometabolic Diseases.

Khalid Sawalha, MD,1 Angel Lopez – Candales, MD FACC FASE,2
1. Cardiometabolic Medicine, University of Missouri – Kansas City, MO.
2. Division of Cardiovascular Diseases, University Health Truman Medical Center, Hospital Hill, and University of Missouri-Kansas City.

Purpose: Approximately 47 million people in the United States are affected by cardiometabolic disorders (CMD), a series of intricated and interrelated factors which increase the risk of developing cardiovascular disease (CVD). Specifically, these factors are represented by a conglomerate of aggregates including abdominal obesity, hypertension, elevated glucose levels or diabetes, and dyslipidemia. The complex interplay of these different entities disturbs metabolic homeostasis resulting in abnormal cellular responses, which not only are responsible for initiating and propagating atherosclerosis but also, for the unfolding of a series of decadent functions that ultimately affect the entire cardiovascular system. As such a collaborative and multifaceted team approach is required to identify individuals at risk of developing CMD but also, provide targeted interventions to lower cardiometabolic risks; hence improve clinical outcomes.

Recent collaborative efforts between cardiologists and endocrinologists among other health care specialists have provided the foundation of such multifaceted team approach, thus creating a new specialty, namely Cardiometabolic Medicine. As entity in flux, the continued evolution of this “new specialty” aims to close the gap between Cardiology and Endocrinology and provide a more effective preventive platform for individuals with altered glucose metabolism or frank diabetes mellitus to mitigate the onset of CVD.

Main goal of training is to highlight the shortfalls of current systems of cardiometabolic care as well as reduce current disparities with regards to age, sex, education, and race/ethnicity. These novel findings inform the need for nationwide clinical and public health interventions to improve cardiometabolic outcomes and health equity.

Methods: Our current Cardiometabolic fellowship curriculum at University of Missouri-Kansas City (UMKC) could become an exemplary format for the training of future Cardiometabolic fellows. As initially conceived, trainees acquire clinical and academic competencies aimed at promoting healthy lifestyles, disease prevention, and specific treatments in an all-inclusive patient environment with the sole purpose of restoring metabolic health, mitigate the development of CVD and promotion of healthy aging and longevity. Figure 1 depicts our UMKC CMD curriculum. Figure 2 explains these rotation details.

Results: To the best of our knowledge, we are the first Cardiometabolic fellowship in the United States with a structured curriculum focusing on different subspecialties as seen in Figure 1. The primary goal of a Cardiometabolic fellowship is to prepare trainees to identify and effectively intervene as well as provide effective follow-up of individuals at risk of developing either diabetes or CVD as well as other cardiometabolic disorders common to both clinical entities in a manner that neither general endocrinologists nor cardiologists are currently trained. With that in mind, the curriculum at UMKC was designed to follow that same principle by offering trainees the necessary tools so they can gain the necessary skills to provide effective primary prevention and to properly identify individuals at risk so that effective interventions can be provided in a timely fashion to mitigate the effects of cardiometabolic disorders. The goal of each cardiometabolic specialist is to acquire the knowledge and develop the confidence to establish treatments and interventions that advanced practice registered nurses, general practitioners, family physicians and internist might not be able to provide so that early recognition of individuals at risk of developing renal disease or CVD can be intervened effectively through effective modification of their metabolic disorders. Early career cardiometabolic specialists have the opportunity to develop a unique niche to develop multidisciplinary ambulatory comprehensive risk reduction programs. Cardiometabolic specialists may also develop and lead innovative programs of population health management that may have broader reach and leverage remote management tools and the expertise of pharmacists and advanced practice providers.

Conclusions: Recognition of Cardiometabolic diseases have allowed us to understand that the continuum of abnormal glucose metabolism until the development of diabetes encompasses numerous pathways and entails the development of a substantial number of clinical entities, of which CVD is the most prominent and most deadly. Unfortunately, the prevalence of Cardiometabolic diseases continues to grow and early recognition is imperative. Consequently, there is great need for the introduction of early and effective preventive measures not only aimed at reducing the development of metabolic abnormalities but also, adverse CVD outcomes. Cardiometabolic training offers a unique force of health care specialists whose training enables them to best equipped in recognizing individuals at an inordinate risk and implementing best practices in primary prevention with the primary goal of reducing atherosclerotic disease and CVD burden. The emergence of Cardiometabolic medicine should close the gap to provide effective treatment and interventions that will ultimately lead to healthier living.

Fred H. D. Charles, MD, MPH, Ahmed K. Abdelrahman, MD, Omar Almaadawy, MD, Mostafa M. Elbanna, MD, Adhvithi Pingili, MD, Aya Allam, MD, Ali Al-Ramadan, MD, Mostafa Elbanna, MD, Omer Ahmed, Khloud Ahmed, MD, Khaled Ali, MD, Adel Elmoghrabi, MD, Luis Afonso, MD.

Wayne State University-Detroit Medical Center, Detroit, MI; Rochester Regional Health Hospital, Rochester, NY; Rosalind Franklin University of Medicine & Science-Chicago Medical School, Chicago, IL; Hackensack Meridian-Jersey Shore University Medical Center, Neptune City, NJ; Menoufia University Faculty of Medicine, Menoufia, Egypt. Medstar Health-Georgetown University, Baltimore, MD.

Purpose: Endothelial function (EF) and arterial stiffness (AS) are important predictors of cardiovascular disease. However, previous research investigating the impact of coffee intake on EF and AS has yielded contradictory results. To address this controversy, we conducted a systematic review and meta-analysis to synthesize the available evidence.

Methods: A comprehensive search was conducted in PubMed and Embase to identify relevant clinical trials examining the effect of coffee intake on EF or AS up to April 2023. The PRISMA guidelines were followed to search the databases. Studies were excluded if they did not include or report pre- and post-caffeine ingestion data for flow-mediated dilation and pulse wave velocity. The mean difference between intervention and control groups for each trial was assessed using the random-effects models. Heterogeneity between studies was estimated using Cochran’s Q and the I2-inconsistency index. The Comprehensive Meta-analysis software (Version 3) was used for the statistical analysis.

Results: Sixteen reports of studies were included for quantitative analysis. Meta-analysis of those
trials revealed a mild increase in means as a (postprandial) effect of coffee intake on combined flow-mediated dilation (FMD) and reflection magnitude as a measure of EF (1.12% [95% CI: 0.42-1.81] p=0.002; I2 = 93.38%), and pulse wave velocity (PWV), a measure of AS, also increased in means (0.77 m/s [95% CI: 0.14-1.41] p=0.017; I2 = 73.69%). Both results are statistically significant.

Conclusions: Coffee use appears to suggest at least a short-term beneficial effect on EF and whereas chronic coffee or caffeine product intake exerts an unfavorable effect on AS measured by PWV.

Nicole Ketter,1,2 Paul D. S. Brown,3 Mathew Vis-Dunbar,3 Brodie M. Sakakibara,1,2,4
1. Graduate Programs in Rehabilitation Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
2. Centre for Chronic Disease Prevention and Management, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
3. Southern Medical Program, Faculty of Medicine, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
4. Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, BC, Canada

Purpose: Cardiovascular disease (CVD) leads global mortality, with around 17.8 million deaths annually and a projected increase to over 22.2 million by 2030. Efforts are needed for primary and secondary CVD prevention due to an aging population and improved survival after CVD events. Modifiable CVD risk factors, including health behaviors and physiological issues like dyslipidemia and hypertension, contribute to CVD development. The identification of efficacious, safe, affordable, and convenient options for primary or secondary prevention of CVD as either monotherapy or adjunct to evidence-based dietary patterns or standard pharmacotherapy is essential. Fruit consumption from Emblica officinalis (EO), a tree native from South-East Asia to Southern China, has been found to have a beneficial effect on CVD physiological risk factors in preliminary clinical intervention trials; however, questions remain regarding the overall effectiveness of EO on CVD risk. Aiming to address this gap, this systematic review and meta-analysis systematically describes the clinical research examining EO and quantitatively assesses the effects of EO on CVD physiological risk factors including blood lipids, blood pressure, and biomarkers of inflammation.

Methods: The Pubmed, Embase, Web of Science, and Google Scholar electronic platforms were searched for relevant randomized controlled trials. Studies were included if they involved adults (age ≥ 18 years) ingesting a form of EO fruit, had clearly defined intervention and control treatments with pre- and post-intervention data, were peer-reviewed, and were written in English. Outcome measures of interest included blood lipids (total cholesterol, triglycerides, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and very low-density lipoprotein cholesterol [VLDL-C]), blood pressure (systolic and diastolic), and inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP]). Studies were excluded if they compared EO with another risk reduction intervention without a usual care control group. The randomized controlled trials were assessed for methodological quality using the Cochrane risk-of-bias version 2 tool, qualitatively described, and quantitatively evaluated using random and fixed effect meta-analysis models. All analyses were performed using RevMan 5.4, at an alpha set at 0.05.

Results: The initial search identified 1739 studies. After 450 duplicates were removed, the remaining 1297 abstracts were screened. Nine randomized controlled trials were included in the descriptive synthesis and quantitative meta-analysis. Included studies followed parallel-group (n = 6) and crossover (n = 3) designs, with EO dosage ranging from 500 mg/day to 1500 mg/day, and treatment duration ranging from 14 to 84 days. Sample sizes ranged between 12 and 150 participants, and participant recruitment for each RCT included healthy males, healthy males and females, male smokers, males and females with dyslipidemia, those with type 2 diabetes mellitus, those with metabolic syndrome, and those with hypertension. Meta-analyses revealed EO to have a significant composite effect at lowering low-density lipoprotein cholesterol (LDL-C; Mean difference (MD) = -15.08 mg/dL [95% Confidence interval (CI) = -25.43 to -4.73], I2 = 77%, prediction interval = -48.29 to 18.13), very low-density lipoprotein cholesterol (VLDL-C; MD = -5.43 mg/dL [95% CI = -8.37 to -2.49], I2 = 44%), triglycerides (TG; MD = -22.35 mg/dL [95% CI = -39.71 to -4.99], I2 = 62%, prediction interval = -73.47 to 28.77), and high-sensitivity C-reactive protein (hsCRP; MD = -1.70 mg/L [95% CI = -2.06 to -1.33], I2 = 0%) compared with placebo.  EO did not have a significant effect on HDL-C (MD = 2.09 mg/dL [95% CL = -0.91 to 5.08], I2 = 86%, prediction interval = -8.09 to 12.27, p = 0.17), systolic blood pressure (MD = -2.75 mmHg [95% CL = -10.41 to 4.90], I2 = 96%, prediction interval = -30.93 to 25.43, p = 0.48) and diastolic blood pressure (MD = -0.83 mmHg [95% CL = -5.87 to 4.21], I2 = 89%, prediction interval = -19.09 to 17.43, p = 0.75).

Conclusions: Considerable heterogeneity exists in the included studies including marked variations in the participant inclusion criteria, baseline biochemical values, study design, duration of treatment, and the potential variation in EO extract preparation techniques. Due to the statistical and clinical heterogeneity, the promising effects of EO on physiologic CVD risk factors in this review should be interpreted with caution. This study did find that EO has beneficial effects on LDL-C, VLDL-C, HDL-C, TG, and hsCRP that are statistically significant. Further research on the clinical effects of EO is necessary with larger randomized controlled trials to confirm these results and identify the most efficacious dose and form of EO. Overall, EO may offer an efficacious, affordable, and convenient option for the prevention or management CVD as either monotherapy or in addition to lifestyle changes or standard pharmacotherapy.

Vuk Vrhovac University Clinic, Merkur Clinical Hospital, Zagreb, Croatia
School of Medicine, University of Zagreb, Croatia

Purpose: Low sex hormone-binding globulin (SHBG) is accompanied with onset of diabetes (DM) and increase in cardiovascular risk (CVR). Elevated inflammatory cytokines account for low plasma SHBG levels, whereas adiponectin (APN) could increase SHBG production. Lipid accumulation product (LAP) as an index, combining waist circumference and triglyceride (TG), advocates as a indicator of increased CVR. We investigated the behaviour of tested CVR factors according to sex in different types of DM and according to LAP.

Methods: Due to the non-normal distribution of individual dependent variables, they were log transformed (HbA1c, HCY, SHBG, IL-6, TG). Differences for analysed variables were tested using two factors analysis of variance (ANOVA) by gender, type of diabetes (DM1, DM2 and latent autoimmune: LADA) and their interaction. ANOVA and Tukey’s post hoc test was also used for testing differences according to LAP quartiles (1st group: LAP < Q1; 2nd group: Q1 ≤ LAP < Med; 3rd group: Med ≤ LAP < Q3, 4th group: LAP ≥ Q3) according to LAP quartiles (women: Q1 = 19.04; Med = 39.04; Q3 = 83.78; men: Q1 = 19.04; Med = 39.04; Q3 = 83.78), separately in women and men. We used regression analysis (stepwise procedure) to estimate st. significant predictors of SHBG and APN separately for each type of DM. For all st. tests, a significance level of 5% was considered st. significant.

Results: Mean age was for women (N=258) was 54.46±16.19 and for men (N=319) 56.09±11.04. Significant difference was determined for SHBG in women according to type of DM. SHBG level was significantly higher in women (especially in DM1) in comparison to men, and in DM1 and LADA in comparison to DM2. There was no difference in SHBG between DM1 and LADA. St. significant interaction indicates that SHBG does not behave approximately equally between men and women according to the type of DM. APN level was significantly higher in women, with no differences according to type of DM The differences according to type of DM and sex were determined for high density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) with higher values in women. HDL and Apo A1 were higher in DM1 and LADA in comparison with DM2, with no st. difference between DM1 and LADA. Significant differences were determined in women and men for Apo A1, HDL, TG and HCY according to LAP quartiles. In women significant differences were determined for SHBG, fasting C-peptide (FCP) and IL-6; the difference for APN was bordered (p=0.068). No difference in APN was observed in men, where the difference for SHBG was bordered (p=0.05). When the differences were significant, higher quartiles of LAP are characterized with increased TG, HCY, FCP and IL-6, whereas SHBG, ApoA1, APN and HDL were decreased. In DM1 main predictors of SHBG were FBG (Partial R2=79%) and sex (19%). Main predictors for APN in DM1 were sex (Partial R2=65%) and IL-6 21%. In DM2 main predictor of SHBG was Apo B (Partial R2=39%), whereas in LADA, HDL was main predictor for SHBG (13%) and APN (68%).

Conclusions: Lower values of SHBG, HDL i Apo A1 in men and in DM2 pointed at higher CVR. APN was significantly higher in women without the difference according to the type of DM suggestion CV protection in women. There was no difference in SHBG, HDL, ApoA1 and APN between DM1 and LADA. Conversely, patients, particularly women, in higher LAP quartiles, are characterized with increased inflammation, dyslipidemia and decreased SHBG, reflecting the importance of central obesity for CVR in women.

Domenica Rubino,1 Zil Patel,2 Jamy Ard,3 Anthony Fabricatore2
1. Washington Center for Weight Management, Arlington, VA;
2. Novo Nordisk Inc., Plainsboro, NJ;
3. Wake Forest University School of Medicine, Winston-Salem, NC.

Purpose: The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the effect of semaglutide (a glucagon-like peptide-1 receptor agonist) on body weight in a diverse group of patients. The objective of this analysis was to examine semaglutide treatment response and tolerability among STEP participants by self-identified racial and ethnic subgroups.

Methods: The STEP studies were US- or global-based, randomized, placebo-controlled, phase 3 trials evaluating the efficacy and safety of once-weekly semaglutide (2.4 mg; subcutaneous). Given similarity of study objectives, design, and population, STEP 1 and 3 results were pooled for analysis. Percent weight change analyses from baseline to week 68 were conducted separately by race (Asian, Black, White, other) and ethnicity (Hispanic or Latino, not Hispanic or Latino, unknown). The primary outcome was the estimated treatment difference (ETD) for semaglutide vs placebo in percent weight change. Adverse events were analyzed descriptively. Analyses addressed the treatment policy estimand. Tests for interaction between treatment and subgroup were performed; P values were not adjusted for multiplicity.

Results: In the pooled sample, the ETD (95% CI) for Asian, Black, White, and other participants were −9.7 (−12.1 to −7.3), −11.6 (−14.3 to −8.9), −12.5 (−13.4 to −11.6), and −9.3 (−12.8 to −5.7) percentage points, respectively. The ETD (95% CI) for not Hispanic or Latino, Hispanic or Latino, and patients with unknown ethnicity were −12.1 (−13.0 to −11.2), −10.9 (−13.1 to −8.8), and −9.6 (−14.8 to −4.3) percentage points, respectively. There was no significant evidence of interaction between the treatment effect and race (P=0.0758) or ethnicity (P=0.4042). The safety of semaglutide was generally consistent across subgroups.

Conclusions: In the pooled analysis, there was no evidence of differences in semaglutide efficacy by race or ethnicity. In all subgroups, the weight loss effect was clinically relevant and the treatment was well tolerated.

Larisa Yedigarova,1 Xi Tan,1 Yuanjie Liang,1 Jigar R. Rajpura,1 Josh Noone,1 Lin Xie,1 Adam de Havenon 2
1. Novo Nordisk Inc., Plainsboro, NJ, USA
2. Department of Neurology, Yale University, New Haven, CT, USA

Purpose: Despite guidelines advocating for their use, there is limited real-world evidence comparing the effects of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is) on the risk of cardiovascular events in individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). This retrospective cohort study compared the time to incidence of ischemic stroke, myocardial infarction (MI), and 2-point major adverse cardiovascular events (MACE; ischemic stroke or MI) while on treatment in new adult users of OW GLP-1 RAs and DPP-4is who had T2D and ASCVD.

Methods: This study used data from the Optum Clinformatics® Data Mart (2017-2021). Patients were followed until drug discontinuation, enrollment end, or an event. Inverse probability of treatment weighting was used to balance baseline characteristics, and survival analyses were conducted to compare risks during exposure, defined as continuous use of either drug.

Results: We found that users of OW GLP-1 RAs (weighted N=25,287) had significantly lower risks of ischemic stroke (HR=0.74 [95% CI, 0.63, 0.87]), MI (0.78 [0.67, 0.92]), and 2-point MACE (0.76 [0.68, 0.86]) compared with users of DPP-4is (weighted N=39,684; all P<0.01).

Conclusions: This study suggests that OW GLP-1 RAs reduce the risk of MI and stroke relative to DPP-4is in individuals with T2D and ASCVD.

Michael Charlton,1 Ivy Tonnu-Mihara,2 Chia-Chen Teng,2 Rakesh Luthra,3 Amy Articolo,4 Anthony Hoovler,4 Chioma Uzoigwe,5
1. Department of Medicine, University of Chicago, Chicago, IL
2. Carelon Research, Wilmington, DE;
3. Health Economics and Outcomes Research, Novo Nordisk Inc., Plainsboro, NJ;
4. Medical Affairs, Novo Nordisk Inc., Plainsboro, NJ;
5. Real World Evidence, Novo Nordisk Inc., Plainsboro, NJ

Purpose: Nonalcoholic fatty liver disease (NAFLD), a condition characterized by excessive fat accumulation in the liver, is the most common chronic liver disease in the US. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD that may lead to cirrhosis or decompensated cirrhosis, liver failure, hepatocellular carcinoma, and the requirement for liver transplantation. The prevalence rates of both NAFLD and NASH have increased and are projected to continue to increase with the rising prevalence rates of type 2 diabetes (T2D) and obesity. A 2023 systematic review estimated the prevalence rates of NAFLD and NASH in North America to be 31% and 5%, respectively; however, there is a paucity of data from real-world settings (e.g., administrative claims from health care providers). This study aimed to estimate the annual prevalence rates of NAFLD and NASH from 2016 to 2020 and assess the demographic and clinical characteristics of patients diagnosed with NASH using real-world data from a large managed care population in the US.

Methods: This observational study used longitudinal medical and pharmacy claims data from the Healthcare Integrated Research Database (HIRD®) to identify patients with NAFLD and NASH, calculate the prevalence rates of NAFLD and NASH, and assess the demographic and clinical characteristics of patients with NASH. Enrollment, outpatient and inpatient medical care, and outpatient prescription use data for individual members of health plans from 15 states across the US are tracked longitudinally in the HIRD®. Patients with ≥1 International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) claim for NAFLD (code K76.0) or NASH (code K75.81) between 1/1/2016 and 12/31/2020 were included to determine annual prevalence rates. Rates were calculated as the number of diagnosed cases divided by the person-years at risk in the given calendar year. Demographic and clinical characteristics and associated medication use were assessed by subgroups and included patients aged ≥18 years with a NASH diagnosis (≥2 entries for ICD-10-CM K75.81 between 10/1/2016 and 10/31/2020), with ≥12 months of continuous medical and pharmacy enrollment before and after the date of first diagnosis of NASH, and without concurrent claim(s) for other liver-related conditions during the study period. Subgroups analyzed were newly diagnosed NASH, pre-existing NASH, NASH with cirrhosis (ICD-10-CM K71.7, K74.6), NASH without cirrhosis, and NASH with Fibrosis-4 Index (FIB-4) scores categorized into low (FIB-4 <1.30), indeterminate (1.30≤ FIB-4 ≤2.67), and high (FIB-4 >2.67) score groups. Descriptive statistics were performed for all study measures.

Results: From 2016 to 2020, annual prevalence rates increased for NAFLD (from 1.01% to 1.39%) and NASH (from 0.10% to 0.15%). The cohort used to assess baseline characteristics included a total of 11,876 patients, comprised of 10,205 and 1671 patients with new and existing NASH diagnoses, respectively. Among those newly diagnosed with NASH, 1104 (10.8%) had cirrhosis, and 2688 had calculated FIB-4 scores (low, n=1701; indeterminate, n=718; high, n=269). Among those with an existing NASH diagnosis, 1104 (66.1%) had cirrhosis and 322 had calculated FIB-4 scores (low, n=174; indeterminate, n=108; high, n=40). More females than males were diagnosed with NASH across all subgroups, with proportions ranging from 52.0% to 63.2%. Mean age was higher in patients with cirrhosis and in patients with high FIB-4 scores: 60.7 years for those newly diagnosed with NASH with cirrhosis, 62.0 years for those with an existing NASH diagnosis with cirrhosis, 61.6 years for those newly diagnosed with NASH and a high FIB-4 score, and 61.4 years for those with an existing NASH diagnosis and a high FIB-4 score. Patients newly diagnosed with NASH with low FIB-4 scores had the lowest mean age (47.1 years) across all subgroups. Across all subgroups, antihypertensives were the most prescribed medications, with proportions ranging from 50.9% to 81.9%. Hyperlipidemia, hypertension, obesity, sleep apnea, and T2D were the top 5 chronic conditions identified among patients with NASH. Hypertension and T2D were most prevalent in patients with cirrhosis; hypertension affected 82.2% and 80.9% of patients with cirrhosis with a new NASH diagnosis or existing diagnosis, respectively, and T2D affected 72.3% and 76.2% of patients with cirrhosis with a new NASH diagnosis or existing diagnosis, respectively.

Conclusions: This study demonstrated an increase in annual prevalence rates for NAFLD and NASH from 2016 to 2020; however, the rates calculated in this study are markedly lower than previously reported estimates. This discrepancy may be attributed to low use of ICD-10-CM codes to report these diseases in claims data. These findings may also suggest that NAFLD and NASH are underdiagnosed in a real-world managed care population in the US. Hence, there is a need for increased awareness of NASH as a serious, progressive, metabolic liver disease that commonly exists together with other chronic disease states such as obesity and T2D. The relatively high prevalence of cirrhosis at the time of diagnosis in this analysis highlights the need for refined diagnostics and treatments that can target this segment at the earlier stages of disease. Consistent with previous studies, NASH was associated with many components of the metabolic syndrome, such as hyperlipidemia, hypertension, obesity, and T2D. Overall, these results reiterate the need for early detection, diagnosis, and intervention to optimally manage patients with NAFLD and NASH.

Jenna Theroux, PharmD,1,2 Adriane Brackett Marino, PharmD, BCPS,1 Madison Hall Wilson, PharmD Candidate,1
1. Wingate University School of Pharmacy, Wingate, NC;
2. Eastowne Family Physicians, Charlotte, NC

Purpose: People with human immunodeficiency virus (HIV) are at an increased susceptibility for cardiovascular disease. Those infected with HIV have a cardiovascular risk that can be as much as twice that of individuals without HIV, leading to a greater likelihood of various cardiovascular complications, such as heart attacks, strokes, heart failure, peripheral arterial disease, and death. The utilization of statins within this demographic is frequently limited and often underprescribed due to concerns for possible drug interactions and limited available guidance. This investigation’s primary intent is to assess the utilization of statins in HIV patients who are at risk, as defined by the AHA/ACC guidelines, for developing cardiovascular disease within an urban family medicine clinic specializing in HIV care. AHA/ACC guidelines classify HIV as a risk enhancer for developing cardiovascular disease.

Methods: A review of electronic medical records from 272 individuals who were prescribed antiretroviral therapy (ART) at an urban family medicine HIV clinic was conducted. The primary intent was to assess whether patients with an indication for statin therapy were prescribed a statin at the proper intensity. Indication was defined as fitting into one or more ACC/AHA statin benefit groups: between the ages of 40 and 75 with diabetes, established clinical atherosclerotic cardiovascular disease (ASCVD), an ASCVD risk score of 7.5% or higher with the risk enhancer of HIV, or an LDL level exceeding 189 mg/dL. Secondary analyses aimed to identify whether certain indications led to more frequent or less frequent appropriate utilization of statins.

Results: Following the analysis and evaluation of the 272 patients, it was determined that 30.14% (n=82) met our defined indication criteria for a statin medication. Less than 50% of patients with an indication for statin therapy received a prescription (41.46%, n=34); however, when statins were prescribed the intensity was most often appropriate. Among those indicated for statin therapy, 21.95% of patients had Type 2 DM aged 40-75 y/o, 8.53% had an LDL exceeding 189 mg/dL, 6.09% had clinical ASCVD, and 63.41% had an ASCVD risk score ≥7.5% with the risk enhancer of HIV.

Conclusions: The risk of cardiovascular disease is increased among people with human immunodeficiency virus (HIV). Life expectancies of individuals living with HIV are increasing, indicating a need to consider cardiovascular risk reduction strategies in this patient population. Our study demonstrates statin utilization is suboptimal, despite existing and emerging evidence of benefit. Incorporating clinical pharmacists into the patient care team can help increase the appropriate prescribing and utilization of statins within the HIV population.

Arrigo F.G. Cicero,1,2 Federica Fogacci,1,2 Marina Giovannini,1,2 Edigio Imbalzano,3 James Ehrlich,4 Elisa Grandi,1 Elisabetta Rizzoli,1 Sergio D’Addato,1
1. Hypertension and cardiovascular risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy
2. Italian Nutraceutical Society (SINut), Bologna, Italy
3. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
4. University of Colorado Anschutz Center, Aurora Colorado

Purpose: In addition to healthy lifestyle and balanced diet, nutraceuticals supplementation may be useful to maintain overall metabolic wellness. The aim of the current study was to assess the metabolic and vascular effects of a new highly standardized bergamot phytocomplex supplementation in healthy volunteers with the features of the metabolic syndrome.

Methods: We carried out a double-blind, randomized, placebo-controlled, three-arm, parallel-group clinical trial in 90 adult subjects treated for 12 weeks with two different dosages of a highly standardized bergamot phytocomplex or placebo. Lipid plasma levels of lipids, glycaemia, plasma hs-CRP, HOMA-IR, body fat, endothelial reactivity and fatty liver index were assessed at baseline, after 6 weeks and at the end of treatment in all subjects.

Results: At the end of treatment, both tested bergamot extract doses were able to significantly improve atherogenic dyslipidaemia and insulin-sensitivity (p<0.05) compared to placebo. In the high-dose treated group, TC, LDL-C, non-HDL-C, and TG improved versus placebo (p<0.05) just after 6 weeks of treatment. After 12 weeks of treatment, TC decreased by 13.2±2.1%, LDL-C by 17.7±3.2%, Non-HDL-C by 17.5±3.1%, TG by 16.6±3.3%, TG/HDL-C by 22.5±4.4%, HOMA-IR by 12.2±2.1%, gGT by 22.2±4.6%, and hsCRP by 17.9±3.4% versus baseline (p<0.05) and vs. placebo (p<0.05). Percentage body fat and endothelial reactivity improved versus baseline, but not versus placebo, in the high-dose treatment only (p<0.05).

Conclusions: The tested bergamot phytocomplex was able to significantly improve glucose and lipid metabolism, as well as inflammation and might represent a novel multi-target approach to control metabolic syndrome.

Katherine R. Tuttle,1 Thomas Idorn,2 Maximilian Jara,3 Mads Sundby Palle,2 Anne-Sophie Sejling,2,3 Henning Grønbæk,4
1. Providence Medical Research Center, Spokane, WA, USA;
2. Novo Nordisk A/S, Søborg, Denmark;
3. Novo Nordisk Inc., Plainsboro, NJ, USA;
4. Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark

Purpose: Chronic kidney disease is a common comorbidity in non-alcoholic fatty liver disease (NAFLD  ). The glucagon-like peptide-1 analogue semaglutide is being investigated in non-alcoholic steatohepatitis (NASH), a severe form of NAFLD. This post-hoc analysis pooled data from three randomized, placebo-controlled, phase 1 or 2 NAFLD trials to investigate the effects of semaglutide on kidney function.

Methods: Data from NCT03357380 (semaglutide 0.4 mg once daily [OD] for 72 weeks in NAFLD), NCT02970942 (semaglutide 0.1, 0.2, or 0.4 mg OD for 72 weeks in NASH with fibrosis stage 1–3), and NCT03987451 (semaglutide 2.4 mg once weekly [OW] for 48 weeks in compensated NASH cirrhosis) were included. Placebo arms were pooled, as were the semaglutide 0.4 mg OD arms in NCT03357380 and NCT02970942, and the semaglutide 2.4 mg OW arm in NCT03987451 (NCT02970942 semaglutide 0.1 and 0.2 mg OD arms were excluded). Annual slope of change in estimated glomerular filtration rate (eGFR) was analyzed for semaglutide vs placebo. Results were analyzed by baseline eGFR: <75 and ≥75 mL/min/1.73 m2.

Results: Baseline characteristics were comparable for semaglutide (n=163) and placebo (n=137). Mean age was 64.7 vs 63.5 (semaglutide vs placebo for eGFR < 75 mL/min/1.73 m2) and 56.0 vs 54.1 (eGFR ≥ 75 mL/min/1.73 m2) years and mean eGFR was 65.9 vs 63.0 and 98.9 vs 98.3 mL/min/1.73 m2, respectively.  In the eGFR <75 mL/min/1.73 m2 group, semaglutide appeared to have a beneficial effect on eGFR (annual slope semaglutide 5.91 mL/min/1.73 m2 [n=19], placebo –1.53 mL/min/1.73 m2 [n=19]; difference 7.45 mL/min/1.73 m2 95% confidence interval [CI] 3.12, 11.74). In the eGFR ≥75 mL/min/1.73 m2 group there was no treatment difference (semaglutide n=144, placebo n=118; difference 0.40 mL/min/1.73 m2 95% CI –1.12, 1.92). The test for interaction between the <75 and ≥75 mL/min/1.73 m2 groups was significant (p=0.0026). Semaglutide did not affect annual change in eGFR vs placebo in the overall population (difference 1.19 mL/min/1.73 m2 95% CI –0.24, 2.62). The difference in slopes was primarily driven by the positive slope in the eGFR <75 mL/min/1.73 m2 group.

Conclusions: In patients with NAFLD and eGFR <75 mL/min/1.73 m2 a potential protective effect of semaglutide on eGFR was observed. Despite the small sample size of this post-hoc analysis, the results support further studies of semaglutide in NAFLD with low eGFR.

Lise Lotte Gluud,1 Stephen A. Harrison,2 Maximilian Kurt Jara,3* Mette Skalshøi Kjær,4 Amine Lotfi,4 Karina Phonekeo,4 Mads Sundby Palle,4 Philip N. Newsome5
1. The Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark;
2. Radcliffe Department of Medicine, University of Oxford, Oxford, UK;
3. Novo Nordisk Inc. Plainsboro, NJ, USA;
4. Novo Nordisk A/S, Søborg, Denmark;
5. Centre for Liver and Gastrointestinal Research, Institute of Immunology and Inflammation
6. National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, The Medical School, University of Birmingham, Birmingham, UK.

Purpose: Semaglutide, a glucagon-like peptide-1 receptor analogue approved for treatment of type 2 diabetes (T2D) and overweight or obesity, is being investigated as a potential treatment for patients with non-alcoholic steatohepatitis (NASH). Here, we present safety data from two phase 2 trials of subcutaneous semaglutide in patients with NASH with or without compensated cirrhosis.

Methods: This was a post-hoc analysis of two trials: NCT02970942 (320 patients with fibrosis stage F1–3 randomized 3:1 to once-daily semaglutide 0.1, 0.2 or 0.4 mg [n=80, 78 and 82] or placebo [n=80] for 72 weeks) and NCT03987451 (71 patients with compensated cirrhosis randomized 2:1 to once-weekly semaglutide 2.4 mg [n=47] or placebo [n=24] for 48 weeks). Patients received diet/lifestyle advice in both trials. Safety data were analyzed descriptively.

Results: In NCT02970942, 18 patients discontinued semaglutide due to adverse events (AEs), with a similar proportion of patients discontinuing in the semaglutide 0.4 mg (5%; 4/82) and placebo arms (5%; 4/80). In NCT03987451, three patients from the semaglutide arm (6.4%) discontinued due to AEs. In both trials, gastrointestinal (GI) disorders were the most common AEs with semaglutide (64–77% vs 33–45% with placebo); most GI AEs with semaglutide were non-serious and mild (55–71%) or moderate (22–36%). The proportion of patients with GI AEs with semaglutide in the NASH trials (63.8–76.9%) was similar to that seen in the weight management program STEP (63.5–82.8%), but higher than in the T2D development program SUSTAIN (34.4–52.0%).
There were no reported cases of acute pancreatitis. Overall, the proportion of patients with hepatic AEs (most frequently reported [in 0–3 patients per arm]: blood bilirubin increased, alanine transaminase increased, hepatic enzyme increased, international normalized ratio increased, transaminases increased, ascites) was 8–11% with semaglutide versus 4–14% with placebo. Few gallbladder-related AEs were reported. Four cholelithiasis events occurred in the semaglutide arms in the two trials; three were serious, of which two led to cholecystitis or cholangitis. All three serious events resolved with cholecystectomy. No cases of drug induced liver injury were reported. Throughout the trials (up to 72 weeks), three patients in the semaglutide group reported malignant neoplasms (breast cancer, endometrial adenocarcinoma and peripheral T-cell lymphoma) vs none with placebo; all events were judged as unlikely to be related to semaglutide.

Conclusions: Data from two phase 2 trials indicate that semaglutide is generally well tolerated in patients with NASH, including those with compensated cirrhosis. No new safety concerns were identified, and the safety profile was similar to that in patients with T2D and overweight/obesity. Data from the ongoing phase 3 trial (NCT04822181) will provide further knowledge about the safety of semaglutide in patients with NASH.

Mingma Sherpa, DO,1 Angela Khidhir, DO,1

Department of Internal Medicine, Jacob’s School of Medicine and Biomedical Sciences, Buffalo, NY

Purpose: Arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC/D) is inherited cardiomyopathy which is caused by desmosomal protein gene mutations, primarily in desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2). It is characterized pathologically by myocardial atrophy, fibrofatty replacement, fibrosis and thinning of the wall with chamber dilatation. Consequently, producing electrical instability precipitating ventricular arrhythmias (VA) and sudden cardiac death (SCD). It is a well-known leading cause of SCD in young adults. There is little information about the association of these mutational consequences in women with various gynecological condition. These desmosomal mutations are considered to be involved in leiomyoma-related bleeding. The estimated prevalence is between 40 and 60% among women under the age of 35 and 70% to 80% among women over the age of 50. As incidences of ARVC/D in women increases, it is challenging to manage along with various other gynecological conditions including leiomyomas, pregnancy and delivery.

Methods: We report a case of a 32-year-old female who presented with exercise-induced palpitations and syncopal episodes.

Results: This case of a 32-year-old female who presented with exercise-induced palpitations and syncopal episodes. She has a history of severe dysmenorrhea but has no medical conditions otherwise. On monitoring, she was found to have a high burden of ventricular premature complexes (VPCs). VAs were thought to have precipitated her syncopal episodes. She was started on antiarrhythmics. Echocardiogram demonstrated right ventricular dilatation and wall thinning. The patient later underwent genetic testing, which confirmed ARVC-associated mutations. Her dysmenorrhea was managed with combined oral contraceptives and nonsteroidal anti-inflammatory drugs. Pelvic ultrasound revealed leiomyomas, which were surgically removed.

Conclusions: This case supports the possible intricate relationship between cardiovascular and gynecological conditions in women. Desmosomes are specialized protein complexes that play a critical role in maintaining the structural and mechanical stability of tissues. Mutations in desmosome genes disrupt the normal functioning of these protein complexes, leading to impaired cell-cell adhesion and increased vulnerability to tissue damage. A collaborative and multidisciplinary approach involving cardiology and gynecology is crucial for optimizing patient care and accomplishing promising results in this population. The next step is to conduct studies to better understand the risk of developing cardiovascular disease in patients presenting with these gynecological conditions and vice versa to provide early monitoring and treatment.

Albert Holler,1 Lukasz Gondek,2 Hua-Ling Tsai,2 Harry Cao,2 Emmanuel S. Antonarakis,3 Sergiu Pasca,2 Cynthia Shams,2 Jiajun Xie,2 Seamus Whelton,4 Michael J. Blaha,4 Samuel Denmeade,2 Jun Luo,5 Catherine H. Marshall,2
1. Johns Hopkins University School of Medicine, Baltimore, MD
2. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
3. University of Minnesota Masonic Cancer Center, Minneapolis, MN
4. Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD
5. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD

Purpose: Standard treatment for metastatic prostate cancer (mPC) includes agents targeting the depletion of androgens, leading to an increase in cardiovascular disease risk factors including elevations in low density lipoprotein (LDL) and triglyceride (TG) levels.  A novel treatment for mPC is bipolar androgen therapy (BAT) that includes giving supraphysiologic doses of testosterone in conjunction with androgen deprivation therapy (ADT), resulting in rapid cycling of testosterone levels. We previously showed that BAT is associated with a reversal of some of the cardiovascular effects of ADT including a decrease in LDL levels, high density lipoprotein levels (HDL) and TG. We hypothesized that these changes might be influenced by the presence of clonal hematopoiesis of indeterminate potential (CHIP), the expansion of white blood cells with hematologic malignancy-associated somatic alterations in a person who does not currently display evidence of hematologic malignancy, which has been associated with an increased risk of cardiovascular disease. 

Methods: This was a retrospective analysis of the RESTORE clinical trial (NCT02090114) – a study of men with metastatic castration resistant prostate cancer, previously treated with ADT and abiraterone/enzalutamide (n=59). Baseline serum was used to identify the presence or absence of CHIP using whole exome analysis, based on the presence of one of 49 genes associated with CHIP with a VAF of at least 2%.  Blood samples were taken at baseline and 3 months after treatment with testosterone cypionate 400mg intramuscularly every 28 days. Cardiopulmonary system events were those reported as adverse events during the clinical trial and included incident hypertension, pulmonary embolism, myocardial infarction.

Results: The median age of the population was 72 years (range 50 – 89), 86% were self-classified as White, 53% were prior smokers and 92% of patients had prior radiation.  CHIP was identified in 12% (7/59, 95% CI: 6-23%) of participants with one patient having 2 clones.  The most common CHIP mutations identified were DNMT3A (n=4), TET2 (n=3), ASXL1 (n=1), and CSF1R (n=1).

There was no difference between those with CHIP and those without CHIP with regards to baseline LDL (median 97 mg/dL, range 38 to 160 versus median 100 mg/dL, range 63 to 177; P=0.6), HDL (median 53 mg/dL, range 29 to 144 mg/dL versus median 60, range 41 to 111; P=0.5) or TG (median 129 mg/dL, range 45 to 368 versus median 148 mg/dL, range 43 to 342 mg/dL; P >0.99).  When comparing the factors after treatment, those with CHIP had lower TG levels at 3 months compared to those without CHIP (median 59 mg/dL, range 48 to 120 versus median 101.5 mg/dL, range 41 to 333; P=0.051), though this greater decline of TG in CHIP group did not reach statistical significance when compared to TG changes in patients without CHIP (decline median of 78 mg/dL versus 16 mg/dL with and without CHIP, respectively. p = 0.26).  There was no difference between those with CHIP and without regards to a 3 month change in LDL or HDL. Overall, total of 6 (10%) patients experienced serious (grade 3 or higher) cardiopulmonary adverse events.  Patients with CHIP had an incidence of cardiopulmonary adverse events of 29% (2/7) vs. 27% (14/52) in CHIP negative patients.  There was no significant association between CHIP and cardiopulmonary events (odds ratio= 1.12, 95% CI: 0.13-6.20, p = 0.90).

Conclusions: In this hypothesis generating study, there were no significant differences in CV risk factors or CV adverse events among those with or without CHIP in response to cancer treatments.  More research is needed to determine how specific CHIP clones, for example TET2 as has been reported in previous studies, may impact these risk factors and events with other cancer treatments. 

Ioan Axente Gutiu,1 Anton Iulian Gutiu,2 Gabriel Constantinescu,1 Stefan Flavian Radulescu,1
1. “Carol Davila” University of Medicine and Pharamcy (Ioan Axente Gutiu, Gabriel Constantinescu, Stefan Falvian Radukescu)
2. Private Medical Office (Anton Iulian Gutiu)

Purpose: Hypomagnesaemia  is implied in atherosclerosis by distinct mechanisms: increased LDL-cholesterol oxidation, leukocytes and macrophages activation, freeing of cytokines, etc. Serum triglycerides (TG) are a biomarkers of cardiovascular disease (CVD) risk, possible by increase of circulating atherogenic particles, interventions on HDL-cholesterol function, etc.. In this work we aimed to study the role of HMg in patients with CVD and high serum TG level. For that we analyzed atherosclerosis risk factors  (dyslipidemia, arterial hypertension, smoking, etc.) and the level of no specific inflammation implied in atherogenesis (CRP serum level, fibrinogenemia (F), leukocytes, etc.).

Methods: In a cross-sectional study we analyzed 905 patients with CVD  (old myocardial infarction, angina pectoris, stroke, peripheral arteritis), mean age 56.5 years, 235 (26%) were  men. The level of HMg was considered for serum Magnesium <=1.75mg% and for TG was considered a serum level >=150mg%. The association of HMg and high level of TG was detected in 134 CVD patients (mean age 57.5 years, 38 (28%) were men; 305 patients have not HMg or/and hypertriglyceridemia (men age 54.5 years, 137 (45%) were men.

Results: Significant statistic differences between traditional atherosclerosis risk factors in patients with HMg and high level of TG  versus no HMg or no high TG were found for: serum Cholesterol (229.3+/-41.3mg% versus 204.9+/-47.3mg%, P<0.001), HDL-Cholesterol (41.7+/-12.1 vs 52.2+/-12.1mg%, P<0.001) and serum glucose (140.1+/-53.2 vs 98.4+/-26.0mg%, P<0.001). Concerning inflammation, comparing patients groups we found:: serum F (466.7+/-120.2mg%, vs 383.4+/-110.3+/-, P<0.023), serum leukocytes (7864+/-2678 vs 7191+/-2003, P<0.006), CRP (8.4+/-6.5 vs 5.1+/-3.8, P<0.001), BSR (16.3+/-9.3 vs 11.5+/-7.5mm at 1h, P< 0.002).

Conclusions: The association of HMg and high TG serum level may be found in 14.8% from CVD patients. In these patients we found a high serum level of some atherosclerosis risk factors such as glucose, Cholesterol and a low level of HDL-Cholesterol.. In addition, we found an obvious increase of no specific inflammation. This is a provisory study with a limited number of patients, but we underline the importance of HMg in high TG level patients for intervention by Magnesium supplement.

Michael Knight, Amanda Velazquez, Zhaoping Li, Goutham Rao, Anthony Fabricatore
1. George Washington University, Washington, DC
2. Cedars Sinai, Los Angeles, CA
3. University of California—Los Angeles, Los Angeles, CA
4. University Hospitals of Cleveland/Case Western Reserve University, Cleveland, OH
5. Novo Nordisk, Inc., Plainsboro, NJ

Purpose: Over 40% of adults in the United States live with obesity; people of color are disproportionally affected (NHANES, 2021). Race and ethnicity may affect identification and treatment of obesity. This study explored the experiences of people of color with obesity (PoCwO) and health care professionals (HCPs) in obesity management.

Methods: Patients diagnosed with obesity were recruited for the study via health care panels. In the qualitative phase, Zoom interviews about experiences with obesity management in PoCwO (body mass index >30 kg/m2; n=40) helped develop the larger quantitative survey. Both PoCwO and HCPs (>70% of time in patient care with a mix of patients from various racial/ethnic groups, 63% primary care providers) completed the quantitative phase surveys.

Results: A total of 1001 patients with obesity who self-identified as Black/African American (n=273), Hispanic/Latinx (n=275), Asian American/Pacific Islander (n=249), and Native American/Alaskan Native (n=204) completed the quantitative survey between Nov 27, 2021 and Mar 2, 2022. For the provider perspective, 150 HCPs were included; 77 self-identified as White/European American, 13 as Black/African American, 13 as Hispanic/Latinx, 45 as Asian American/Pacific Islander, and 2 as Native American/Alaskan Native.
Approximately 7 in 10 PoCwO reported a belief that race/ethnicity left them disadvantaged in health care interactions, and ~3 in 10 PoCwO sensed biases about race/ethnicity regarding their weight from HCPs during their first conversation. PoCwO were more likely to feel comfortable initiating conversations about weight management with an HCP of the same race/ethnicity vs a different race/ethnicity (54% vs 47%). Conversely, PoCwO with an HCP of a different race/ethnicity were more likely to have felt the tone used was condescending (11%) or overly critical (9%) vs those seeing a same-race/ethnic group HCP (≤4% for both terms). Of PoCwO who felt HCPs made assumptions about race/ethnicity in relation to their weight, fewer than half challenged those assumptions (eg, cultural dietary preferences); however, 71% still see the same HCP as was seen at their first conversation.
Approximately 40% of PoCwO desired more tailored advice (eg, racial/ethnic considerations), and 90% of HCPs were willing to receive education on cultural factors for more tailored conversations. Surveyed HCPs suggested PoCwO may have barriers to access to care; further education about which barriers exist and how to overcome them could be beneficial to patient care.

Conclusions: In this study, PoCwO indicated that perceived HCP biases about their race/ethnicity negatively impacted the care received for obesity management. Also, PoCwO felt more comfortable initiating conversations about weight with HCPs of similar race/ethnicity. Mitigating racial/ethnic assumptions among HCPs through further education and increasing the number of HCPs of color are potential steps toward improving care of PoCwO.

Yineli Ortiz MD,1 Gabriel Mora MD,1 Astrid Aviles MD,1 Ivan Rivera MD,1 Michelle Mangual MD,1 Jose M. Garcia Mateo, MD,1 Alejandro Lopez Mas,1
1. San Juan City Hospital, San Juan PR

Purpose: Patients with hyperthyroidism have increased risks of an array of cardiovascular problems, such as: atrial fibrillation, hypertension, coronary artery disease, stroke and heart failure. Thyroid disease are common with cardiac disease patient, reaching 11%. Thyroid dysfunction affects cardiovascular physiology by different means, including myocardial inotropy, heart rate, cardiac output and peripheral arteries reactivity. Coronary artery calcium (CAC) on computed tomography (CT) is a well validated measure of subclinical atherosclerosis. It has been shown to be useful way of improving cardiovascular risk assessment in asymptomatic individuals with risk factors for atherosclerotic cardiovascular disease (ASCVD). It serves as a guide for initiating or deferring preventive therapies. Hereby, we describe the case of a patient presented with overt hyperthyroidism with substernal goiter and high risk for ASCVD  above 20% but with normal levels of LDL on which a coronary artery calcium score served as a predictive tool for risk stratification.

Methods: This is a case of a 61-year-old male with past medical history of arterial hypertension, and chronic obstructive pulmonary disease secondary to heavy smoking who was referred by his PCP for further evaluation of altered thyroid function tests (TFTs). On the initial evaluation, patient complained that over the last 2 months he had being dealing with: palpitations, tremors, heat intolerance, neck enlargement, fatigue and sweating.The physical exam was remarkable for tachycardia on auscultation, a palpable goiter, the presence of Pemberton’s sign and increased deep tendon reflexes. Thyroid ultrasound was ordered which revealed a diffuse goiter with possible extension to substernal area. Laboratory results showed a suppressed TSH level (< 0.008 uIu/ml), elevated free T4 level (1.98 ng/dl) and total T3 uptake of 52% consistent with an overt hyperthyroid state. Patient was started on methimazole 30 mg daily in order to control hyperthyroidism.On laboratory patient evaluation noted with a normal LDL (70 mg/ dl)  and Non-HDL (95 mg/dl) levels but with High risk for ASCVD (> 20%). Despite having such high ASCVD risk patient is reluctant to start statin therapy.

Results: Chest CT scan was ordered due to possible goiter with substernal extension and based on his reluctant to start statin therapy a coronary Calcium was order to look for subclinical ASCVD in the same imaging study. Substernal Goiter extension was confirmed on chest CT and coronary calcium score was reported elevated at 680, leading to ASCVD risk of more than 30%. Based on these results, cardiology evaluation was recommended before total thyroidectomy surgery. It also helped the patient to better visualized his risk and understand the importance of starting evidence based high intensity statin for LDL lowering.

Conclusions: CAC score as a tool is accessible, non invasive and requires minimal patient preparation. It gives us a summary measure of atherosclerotic disease, reflecting the cumulative lifetime effect of both measurable and unmeasurable risk.CAC score has emerged as the single most predictive cardiovascular risk marker in asymptomatic individuals as in our patient with multiple risk factors but with a normal LDL and Non-HDL levels. Despite the limited data regarding this type of use for Calcium score , not only it was helpful as a more visually understandable tool to convince this patient about the need of use statins as primary prevention to decrease the risk of a first cardiovascular event but also to guide our clinical decision and referred the patient for adequate cardiovascular evaluation before establishing definitive management regarding his hyperthyroidism state ,substernal large goiter and avoid postoperative complications.

Sumanth Khadke, Ashish Kumar, Sadeer Al-Kindi, Sanjay Rajagopalan, Khurram Nasir, Javaria Ahmad, Gary Adamkiewicz, Scott Delaney, Sourbha S. Dani, Sarju Ganatra

Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA.
Department of Medicine, Cleveland Clinic, Akron General, Akron, Ohio, USA.;
Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Cardiovascular Center, Houston, TX.
Harrington Heart and Vascular Institute, University Hospitals and Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, TX, USA.
Department of Environmental Health, Harvard T.H. Chan, School of Public Health, Boston, MA, USA. 
Department of Cardio-Oncology, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA

Abstract not permitted to be published by authors

Specific affiliation not indicated.

Maltos-Gómez F1,2 Muñoz-Comonfort A2, Martínez-Tapia R2, Hernández-Chávez AA2, Castellanos-Martínez JA2, López-Chavira L2, Sampieri-Cabrera R2*
1. General Direction of Quality and Education in Health scholar, Department of Health, Mexico;
2. Department of Physiology, National Autonomous University of Mexico, Mexico City, Mexico

Purpose: Cardiovascular health is a topic of significant relevance nowadays, as cardiovascular diseases continue to be one of the leading causes of morbidity and mortality worldwide. Methodological approaches to the prevention of these diseases have primarily focused on identifying risk factors and predicting the risk of developing cardiovascular problems within a specific time frame. However, it is crucial not to limit ourselves solely to these predictive approaches but to also consider estimations that allow us to assess cardiovascular health itself, as well as the factors and behaviors associated with this state.
In this context, this study aims to analyze the behavioral determinants of factors and behaviors related to cardiovascular health in a population of young adults. The main objective is to identify the behaviors and factors that influence the cardiovascular health status of this population and gain a better understanding of the interactions between these elements.

Methods: The study was conducted using a retrospective cohort design involving 54 participants from the School of Medicine. To assess cardiovascular health, criteria established by the American Heart Association were employed, which encompass ideal cardiovascular health behaviors (non-smoking, a body mass index <25 kg/m2, a very active level of physical activity, and daily consumption of ≥3 servings of fruits and vegetables) and factors (total cholesterol level <200 mg/dL, blood pressure <120/80 mmHg and fasting capillary glucose level <100 mg/dL without the need for treatment, and not smoking). With these components an ideal cardiovascular health index ranging from 0 to 7 was created, where a score of 7 represented an ideal cardiovascular health status.
Data were collected through anthropometry, the body composition analyzer InBody270, capillary blood samples processed by Accu-chek and Accutrend Plus meters, and online surveys using Google Forms, which included the Lipid Research Clinics questionnaire, Beck’s Depression Inventory, Pittsburgh Sleep Quality Index, PrimeScreen questionnaire and a clinical chart. The information was analyzed using Access, SPSS and Excel. Descriptive statistics such as mean, standard deviation and percentages were calculated, and chi-square tests, t-tests, U Mann Whitney tests, Kruskal Wallis test, ANOVA, and Pearson and Spearman correlations were performed to analyze relationships between variables.
In addition to quantitative analyses, a qualitative study was conducted, involving in-depth interviews with participants who achieved high and low scores on the cardiovascular health index. These interviews aimed to explore contextual and personal factors that might be related to the participants’ cardiovascular health status.

Results: The sample consisted of 15 males and 39 females with an average age of 19.3 ± 1.2 years (mean ± standard deviation). Regarding the ideal cardiovascular health index, the mean score was 4.1 ± 1.18, and no significant differences were observed between males and females (p = 0.57). However, it is important to note that only 13% and 30% of participants achieved scores of 6 and 5, respectively, indicating a relatively low level of compliance with ideal cardiovascular health criteria. Surprisingly, 58% of subjects obtained a score equal to or less than 4, highlighting the need for preventive interventions in this population.
It is noteworthy that none of the participants achieved all seven components of the ideal cardiovascular health index, suggesting that there is ample room for improvement in the adoption of ideal cardiovascular health behaviors and factors.
Upon conducting a more detailed analysis of the variables, only 11% of participants were classified with an ideal physical activity. Moreover, a significant difference in physical activity was found between men and women (p = 0.001); 3% of women vs 33% of men were very active. In addition, only 57% obtained an ideal fasting capillary glucose level. Furthermore, a significant difference was found in fasting capillary glucose between men and women (p = 0.027) with 67% of women vs 33% of men with ideal levels. Additionally, 57% and 49% were non-smokers and had an ideal intake of fruits and vegetables, respectively.
In the in-depth interviews, contextual and personal factors that might influence participants’ cardiovascular health were explored. An important finding was the relevance of participants’ mental health status as a factor that could have a significant impact on their cardiovascular health. This highlights the importance of addressing not only physical factors but also emotional and psychological aspects in cardiovascular disease prevention.

Conclusions: In conclusion, the results of this study indicate that the prevalence of ideal cardiovascular health in the studied population of young adults is low, and there is significant room for improvement in the adoption of ideal cardiovascular health behaviors and factors. The identification of a low prevalence of physical exercise, ideal glycemic control in men, non-smokers and ideal dietary patterns, and its impact on cardiovascular health, suggests that taking measures on these components could be an effective strategy in preventing cardiovascular diseases in this population.
Additionally, the in-depth interviews revealed the importance of participants’ mental health status in their cardiovascular health, emphasizing the need to address emotional and psychological aspects in prevention strategies. Based on these findings, the implementation of cardiovascular risk factor prevention strategies, including interventions to promote physical exercise, glycemic control, smoking cessation, healthy dietary patterns and mental well-being in this population, is proposed.
This study provides valuable information about the factors and behaviors that influence the cardiovascular health of young adults and underscores the importance of a comprehensive approach to cardiovascular disease prevention. These conclusions can serve as a basis for the development of intervention programs and public health policies aimed at improving cardiovascular health in this population.

Evaluation of real-world treatment outcomes among women 50 years of age and older who were treated with statin + ezetimibe or statin monotherapy in France and Spain

Paula Chu,1 Amy Zhao,2 Ryan Irvine,3 James Li,3 Gordon Goodall,1
1. Organon International, Lucerne, Switzerland
2. Net2Source Inc., Somerset, New Jersey
3. Organon & Co., Jersey City, New Jersey

Purpose: Background and aim: Statins have demonstrated efficacy in reducing major cardiovascular events, yet individuals undergoing statin therapy alone may not consistently achieve the desired reduction in low-density lipoprotein-cholesterol (LDL-C), which could leave them at continued risk. In such scenarios, increasing the statin dosage or introducing adjunctive nonstatin lipid lowering agents such as ezetimibe is often prescribed, aligning with clinical best practices. Despite this, empirical real-world (RW) evidence on the clinical advantages of including an add-on therapy remains scarce, especially among women aged 50 years and older. Given this evidence gap, the present study assessed the goal attainment (based on 2021 European Society for Cardiology (ESC) Guidelines on cardiovascular disease prevention in clinical practice) and percentage (%) change in LDL-C and compared outcomes among women ≥50 years of age receiving combination therapy versus those receiving statin monotherapy in France and Spain. These data may yield valuable insights into the effectiveness of the treatment approach within this demographic.

Methods: In this retrospective analysis, data were obtained from primary care electronic medical records in France and Spain through The Health Intervention Network (THIN) database. The study focused on women aged ≥50 years, who received either statin monotherapy or combination therapy between 2017 and 2020. The sample population had a 12-month baseline period before the initial treatment date with a follow-up period of at least 12 months, a minimum of 4 weeks of continuous treatment with the prescribed lipid-lowering therapy, and LDL-C tests within prespecified windows. To mitigate potential confounding effects, propensity score matching was performed; the treatment groups were matched by age group (categorized as 50-69 and ≥70 years), cardiovascular disease (CVD) risk (high or very high risk per 2021 ESC guidelines), and statin intensity (low, moderate, high). The covariates in the multiple regression analyses for % change in LDL-C and goal attainment included treatment group, age group, CVD risk, statin intensity, and baseline LDL-C value. Analyses were performed separately for each country.

Results: Following propensity score matching, data for 370 patients in France (185 each in the combination and monotherapy groups) and 232 patients in Spain (116 in each group) were analyzed. In France, the majority were ≥70 years old (54.5%), had high CVD risk (51.3%), and were receiving moderate intensity statin therapy (77.8%). In Spain, 56.9% were ≥70 years old, 54.3% had high CVD risk, and 74.1% received moderate intensity statin therapy. In both countries, patients who received combination therapy compared with monotherapy were more likely to achieve goal attainment [France: 12.4% vs 7.0% respectively; odds ratio (OR): 2.07, 95% CI: 1.00-4.29; Spain: 22.4% vs 5.2% respectively; OR: 8.54, 95% CI: 3.08-23.66]. Baseline LDL-C was a significant factor that showed strong association with goal attainment, while age, CVD risk, and statin intensity were not significant. Patients receiving combination therapy also had greater LDL-C reductions from baseline (15.4% vs 8.4%, p=0.029 in France and 16.7% vs 4.8%, p=0.0005 in Spain) compared with monotherapy.

Conclusions: Conclusion: In conclusion, this RW evidence study revealed that women aged 50 years and older who received combination therapy were more likely to attain LDL-C goal targets compared with statin monotherapy. Furthermore, this cohort experienced a substantial reduction in LDL-C levels during the follow-up period when compared to matched cohorts receiving statin monotherapy. While combination therapy improved LDL-C levels, this study highlights the need for proactive lipid management to achieve the known CV benefits and ensure compliance, given the low overall goal attainment. Additionally, the study also emphasizes the significance of RW data in delineating actual outcomes versus what is achieved in controlled clinical trials.

Gayathri Badrinath,1 Elena Kamel, MD,2 Rupa Sanghani ,MD,3 Annabelle Santos Volgman, MD,3 Ashley Walsh, NP,2 David Maggs, MD,1 Wendy Satmary, MD,1 Agustin Collazo Mayer,1 Kalil de Lima Moreira,1
1. Devyn, Los Altos, CA
2. Northwestern Univ, Chicago, IL
3. Rush Univ Medical Ctr, Chicago, IL

Purpose: Women with adverse pregnancy outcomes (APOs), such as gestational diabetes mellitus (GDM), face a markedly higher risk of cardiovascular disease. Despite wide use of technology such as smartphones among pregnant women, little implementation of technology has occurred at scale to simplify the management of APOs peri- or post-partum. We evaluated the feasibility of a user-centered mobile app to engage women with GDM after diagnosis that simplifies self-monitoring and provides evidence-based education.

Methods: For the initial deployment, we developed an iOS and Android-compatible mobile app accessible in the USA (Devyn, Los Altos, CA) through the App Store or Google Play. Users were referred by clinicians from one of 6 sites or signed up through the app. Users entered self-reported data for glucose, blood pressure, physical activity, weight, and medication intake. Users also tracked food intake using text descriptions and/or food photos. Data on in-app user behavior was used to understand which educational articles or recipes users accessed most often as well as identify opportunities for new features and improvements.

Results: We report preliminary findings in 92 users who registered between May 2022 and May 2023. 51% of users signed up via site referral and 49% signed up directly through the app. 63% reported coverage by employer or commercial insurance, 12% Medicaid and 25% other.

71 users logged 13,328 observations. Fifty-six percent of observations were glucose values and 42% were food (breakfast (25%); lunch (23%); dinner (23%); snack (29%)). Users who logged for more than one day entered an average of 5 observations per day.

68% of fasting glucose levels reported were 95 mg/dL. 83%, 81% and 76% of postprandial glucose observations after breakfast, lunch, and dinner, respectively, were 130 mg/dL. Times between food and glucose logging varied between meals and users.

Conclusions: Use of smartphone apps in pregnant women with APOs such as GDM is feasible. Smartphone apps provide advantages in accessibility and can provide meaningful data to advance knowledge of APOs, engage patients and assist in transition of care in real-world settings at a much broader scale than single center initiatives. Future research will help determine if this app can decrease complications of GDM.

Mansur Shomali, MD, CM,1 Abhimanyu Kumbara, MS,1 and Anand Iyer, PhD,1
1. Welldoc, Inc.

Purpose: Individuals with type 2 diabetes should be treated holistically to improve cardiovascular risk factors such as blood pressure and excessive body weight. In practice, helping these individuals with episodic coaching may not be sufficient. We wished to examine the effects of providing individuals enrolled in a virtual health program for type 2 diabetes with a digital health application that provides continuous AI-driven coaching supporting self-management behaviors.

Methods: These data come from a real-world study of individuals with type 2 diabetes enrolled in a pilot virtual program focused on improving nutrition and optimizing medications. As part of the program, individuals were given access to the digital health application. Data from the application was collected from the cloud and de-identified. Data was analyzed from a baseline 2-week period and compared to the most recent 2-week period.

Results: Sixty-five participants were included who were enrolled in the program for greater than 30 days. The mean number of days participants were engaging with the app was 256 days (SD 104, range 49 to 419 days). Sixty-eight percent were female. The greatest number of participants (46%) were in the 55-to-64-year age range. The average BMI at baseline was 37.4 kg/m2. The mean pre-meal blood glucose (138 mg/dL) did not change from baseline. There was a non-significant trend in the improvement of the post-meal blood glucose (158.3 to 148.1 mg/dL, p=0.2) There were significant reductions in systolic blood pressure (129.2 to 122.2 mmHG, p=0.01). The average weight at the endpoint was significantly lower than the baseline (227.8 to 211.8 pounds, p=0.007). Seventy-seven percent of participants lost weight. Of those who lost weight, the average weight loss was 4.8%.

Conclusions: The use of a digital health application in a virtual program for people with type 2 diabetes was associated with favorable trends in post-meal blood glucose and statistically and clinically significant improvements in weight and systolic blood pressure. Digital health tools with AI-coaching have the potential to amplify the benefits of episodic meetings with clinicians and may thus reduce cardiovascular risk.

Douglas R. Corsi, BS, Jenny Dong, Steven R. Muller, Bayanne Kakhia, Serge A Jabbour, MD, Cheryl Marco, RD, CDE, Cynthia Cheng MD, PhD
1. Sidney Kimmel Medical College
2. Department of Family and Community Medicine
3. Thomas Jefferson University

Purpose: Obesity and depression are estimated to affect 34.6% and 7.2% of American adults, respectively. These increasingly prevalent diseases are both linked to substantial morbidity and mortality along with increased risk of cardiovascular disease3. Risk factors for the development of both conditions include female gender, low-income status, and limited education. Individuals with depression are at increased risk for obesity and vice versa. Among depressed adults, obesity prevalence is 43%, compared to 33% in non-depressed adults. Weight gain, regardless of BMI, can negatively affect long-term mental health.

Shared pathophysiologic mechanisms of these commonly comorbid conditions include inflammation, neuroendocrine dysfunction, genetics, and behavioral and psychosocial factors.  Effective interventions that address both ailments are imperative. Growing evidence shows improvements in both weight and depression with increased physical activity. Previous trials have reported enhanced mental health status resulting from a weight loss intervention. We have expanded upon this work by studying whether our intervention promotes motivation for health-related behavioral change. Based on social determination theory, autonomous motivation is a measure of internalized motivation for change, with higher autonomous motivation associated with more sustained change. Our study aims to assess the effectiveness of a low-cost, student-run nutrition education program in obese adults for improving weight, depression, and autonomous regulation for weight loss.

Methods: Enrolled patients were randomized to usual care, or to participate in the Jefferson Weight Loss Program (JeffWLP) intervention delivered by student health coaches, overseen by a certified obesity management physician, in consultation with a registered dietician. Treatment included weekly group and individual nutrition education counseling virtual (Zoom) sessions utilizing motivational interviewing, meal replacements, and an incrementally increasing walking exercise component. Physical activity was assessed using daily step counts recorded using the Outwalk mobile application, along with actigraphy at study baseline, 6 weeks (midpoint), and 12 weeks (endpoint). Vital signs, PHQ9, and TSRQ questionnaires were also performed at these time points. The Patient Health Questionnaire (PHQ-9) is a validated tool for diagnosing and assessing severity of depression.  PHQ-9 scores of 5, 10, 15, and 20 indicate mild, moderate, moderately severe, and severe depression, respectively. A PHQ-9 score of 10 or higher is commonly used to identify clinical depression. The treatment self-regulation questionnaire (TSRQ) is a validated tool for measuring autonomous motivation. Two versions of the TSRQ were used to measure autonomous regulation of JeffWLP participants. The TSRQ Entering the Weight Loss Program was administered at baseline, and the TSRQ Continuing Program Participation was administered at midpoint and endpoint.

Results: In this randomized controlled pilot study, 30 obese adults from an urban population were randomized to intervention (n=18) or control (n=12) groups. The average age was 46 years, 80% were African American, and 90% were female. The prevalence of depression indicated by PHQ-9 >10 at baseline in the entire study cohort was 17%. As will be reported uniquely in another upcoming research meeting, JeffWLP participants achieved statistically and clinically significant weight loss at completion of the 12-week program. PHQ-9 scores progressively improved throughout the program with significant improvement in PHQ-9, from 4.9 + 4.6 at baseline to 3.1 + 3.3 at study end, indicating a change from mild depression to no depression, representing a drop of 1.7 + 2.7 (p = 0.03) at program completion. Autonomous regulation after enrollment increased 0.83 + 1.0 (p = 0.01) from baseline to program completion. An increase in weekend steps walked was correlated with improvement in PHQ-9 scores (R= 0.8, p = 0.03). However, improvement in depressive symptoms or autonomous regulation did not correlate significantly with class participation or weight loss at the endpoint.

Conclusions: To our knowledge, this is the first randomized controlled trial to evaluate the psychological benefits of a low-cost, student-run nutrition education program in obese adults. Participants in the JeffWLP demonstrated significant improvement in both depressive symptoms and autonomous regulation, affirming the program’s positive impact on mood and fostering self-determination. Higher autonomous motivation is associated with a higher likelihood of sustaining desired change, supporting the maintenance of healthy behaviors and eating habits long term. Although the observed change in autonomous regulation after three months was modest, we anticipate and will assess continued improvement over time. Additionally, the positive correlation between step count and depressive symptoms is consistent with the association noted in previous research between increased physical activity and improved depressive symptoms.
The goals of our program extend beyond weight loss; improved nutrition, physical activity, and cardiovascular risk are also emphasized. While our findings are limited by the small sample size and short duration, the positive results, despite these limitations, are promising. The program is ongoing, and we anticipate continued, sustained improvements as we accrue and follow more participants over time.
The significance of this study also has potential far-reaching applications, as the program can be readily replicated by other medical schools. Our protocol provides a low-cost and effective resource for treating both obesity and depression, potentially at the national level. It also contributes to the growing body of evidence supporting the value of weight loss program interventions to address both obesity and depression. Our findings are unique as this is the first low-cost student-run program with demonstrated efficacy for weight loss, increase in activity, and psychosocial benefit. By providing a successful weight loss methodology that also improves mood and autonomous regulation, we hope to inspire further initiatives that promote healthier lifestyles and psychological well-being of obese individuals nationwide.

Ethan Le, BS,1 Joyce Bian, BA,1 Sandra Yang, BA,1 Jennifer Zhan, BA,1, Kameron Inguito, BA,1 Shaheen Soltani,1 Serge A Jabbour, MD,2 Cheryl Marco, RD,2 Erin Galuchie, RD,2 Cynthia Cheng MD, PhD,1
1 .Department of Family and Community Medicine, Thomas Jefferson University Hospital, Philadelphia,
2. Department of Endocrinology, Thomas Jefferson University Hospital, Philadelphia, PA

Purpose: Long-term weight loss maintenance is a significant problem following initial weight loss, with disproportionately high dropout rates previously reported for ethnic/racial minorities, women, and individuals with lower socioeconomic status. Patients in Philadelphia, PA, which has one of the highest obesity prevalence rates in the United States, are particularly in need of sustained, effective, weight loss interventions to treat obesity and prevent comorbidities. Oftentimes, individuals seek care but terminate treatment early before learning strategies required for effective weight loss maintenance. Identifying demographic factors that may affect attrition rate could help target patients at greater risk of dropout for more intensive intervention. Predictors of attrition in previous studies have included younger age, female sex, lower education, and unemployment, along with higher baseline depression symptoms and initial weight loss failure. This study aimed to assess the utility of available demographic risk factors for predicting weight loss maintenance and program retention in a long-term urban hospital medical nutrition therapy (MNT) program utilizing short-term VLCD followed by longitudinal maintenance nutrition counseling to promote sustained weight loss.

Methods: Initial data from 109 participants from a larger cohort (N=275) in Thomas Jefferson University’s MNT program from 2013-2022 were retrospectively analyzed. Demographic factors including age, gender, and race along with baseline BMI and Cumulative Illness Rating Scores (CIRS) were assessed for each patient, along with outcome variables: weight change, duration of program participation (Program Time), total attended sessions (Total Sessions), ending CIRS, systolic and diastolic blood pressure (SBP/DBP), blood glucose, and lipid levels. Demographic variables were analyzed as predictors of outcomes using multiple regression.

Results: Within the 109 pilot patient cohort, 70.6% were female and 11.9% were African American. Average age and starting BMI were 51.2±12.7 years and 38.3±9.5, respectively. As previously reported, average program participation was 31.5±25.0 months and 45.9±33.1 sessions, with resulting 4.6%±8.5% body weight loss (p<0.001), 3.4±9.4 mg/dL HDL increase (p=0.003), and 13.7±59.9 mg/dL triglyceride decrease (p=0.054).
Novel analysis indicates that male patients (p=0.0006) and patients with higher starting BMI (p=0.0166) lost more weight than females following participation in the MNT program. Neither gender, race, nor starting CIRS were associated with program attrition. Additionally, no demographic factors were significant predictors of changes in lipid levels (total cholesterol, LDL, HDL, triglycerides).

Conclusions: Unlike previous studies, the Jefferson MNT program successfully retains participants across varying demographics (age and gender). Consistent with previous literature, patients starting with higher BMI experienced greater percent weight loss. However, male patients were significantly more likely to lose weight over an average of three years of program participation compared to females in previous similar-duration studies. A possible explanation is that long-term self-regulation of calorie intake and attending education based sessions may inspire a greater sense of personal control, which may be more important to males than females. Males may also have higher baseline calorie consumption and metabolic rates than females, increasing the effectiveness of calorie restriction. Future work to improve weight loss retention should investigate patient preferences on program design, such as modality or more personalized counseling sessions. 
Our previously reported data also shows beneficial metabolic outcomes over an average of nearly three years, with triglyceride/LDL decreases and HDL increases associated with longer program participation. New analysis of this pilot data identified no significant demographic predictors of lipid outcomes, demonstrating the program is equally effective at reducing dyslipidemia risk across all demographics studied.
The lack of differential adherence associated with demographics is a positive finding for the program, indicating its ability to retain participants, promote sustainable weight loss, and improve cardiometabolic health across diverse groups. However, we did not examine psychosocial factors that could predict weight loss, attrition rate, and improvements in metabolic outcomes. Alongside completing data collection for the entire 12-years of available data, we plan to evaluate psychosocial predictors with the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder-7 (GAD-7) questionnaires to assess for depression and anxiety. In conclusion, our long-term weight loss counseling program shows sustained success across different demographics in obese and overweight adults, delivering sustained weight loss and metabolic benefits.

Ildiko Lingvay,1 Ofri Mosenzon,2 Katelyn Brown,3 Xuewei Cui,3 Laura Fernández Landó,3 Hiren Patel,3 Dionisios Rentzeperis (Non-author presenter),3
1. Southwestern Medical Center, Dallas, USA
2. The Hadassah University Hospital-Ein Kerem, Jerusalem, Israel
3. Eli Lilly and Company, Indianapolis, USA

Purpose: Tirzepatide (TZP) is a GIP/GLP-1 receptor agonist approved for the treatment of type 2 diabetes in adults. Across the SURPASS 1-5 clinical studies, TZP 5, 10 and 15 mg demonstrated significant improvements in HbA1c (-20.77 to -28.42 mmol/mol) (-1.9 to -2.6%), body weight (-6.6 to -13.9%) and systolic blood pressure (SBP) (-2.8 to -12.6 mmHg) at primary endpoint.

Methods: Patients were randomized 1:1:1:1 to TZP 5 mg, 10 mg, 15 mg or comparator, except in the SURPASS-4 study where patients were randomized 1:1:1:3. Primary endpoint was 40-weeks for (SURPASS-1, 2 and 5) and 52-weeks for (SURPASS-3 and 4). Post-hoc mediation analyses were conducted to evaluate weight loss dependent (WL-D) and independent (WL-IND) effects of TZP on SBP reductions across 5 SURPASS studies. Weight loss was considered an indirect effect (mediator), the effect not mediated by weight loss was considered a direct effect of tirzepatide on SBP. Correlation between SBP change and weight change was also conducted with pooled data of SURPASS 1 to 5.

Results: Concomitant antihypertensive medications were allowed during the SURPASS studies and 47% (SURPASS-1) to 93% (SURPASS-4) of patients were using anti-hypertensive medications at baseline. The difference in mean SBP change from baseline at 40-weeks (Total effect) between TZP and comparator group was -1.3 to -5.1 mmHg (TZP 5 mg), -1.7 to -6.5 mmHg (TZP 10 mg) and -3.1 to -11.5 mmHg (TZP 15 mg). The contribution of WL-D and WL-IND effects on these treatment differences are presented below. In SURPASS-4 study which enrolled patients with established cardiovascular disease, WL-IND effects explained 33% to 57% of difference in SBP change between TZP and insulin glargine groups, with the remainder of 67% to 43% of the effect being WL-D. In a pooled analysis of SURPASS 1-5 studies, there was a significant (p<0.001) but weak correlation (r = 0.18 to 0.22) between change in body weight and SBP.

Conclusions: In conclusion, TZP induced SBP reduction was largely mediated through weight loss, with different degrees of contributions from weight loss independent effects across the different trials.

AG Palladino-Davis,1 Maj Mossaab Benhammou,2 Matthew J. O’Brien,1 Anthony J. Pick,1
1. Northwestern University
2. Loma Linda University

Purpose: Given that Obstetrics and Gynecology offer a life-cycle continuum, and specifically that obstetrical patients are in an innate position requiring ongoing healthcare access and services, we focused on this population to leverage and centralize the existing Northwestern Medicine Lake Forest Hospital community resources and intentionally provide referral services for these to improve the health of this patient population via Lifestyle Medicine (LM). For the Purposes of our program, we are recruiting women with gestational obesity as this provides an opportunity to refer and prescribe the need for lifestyle modifications. In the United States, roughly 42% of the population is obese. Gestational obesity increases not only morbidity and thus heightens complications during the pregnancy, intrapartum, and postpartum periods. Furthermore, at the epigenetic level, these alterations begin in-utero. Operationalizing LM allows for improved outcomes during pregnancy and postpartum, but also it has the capacity to impact the offspring’s health and cardiometabolic disease predisposition.

Methods: Recruitment of patients continues to be ongoing at the time of this submission, as our current pilot program is establishing the basis for designing a Lifestyle Medicine program. Patients are chosen based of diagnosis: gestational obesity, obesity, PCOS, pre-diabetes, gestational diabetes, type 1, and type 2 diabetes, with emphasis of gestational obesity.

Results: Chronic conditions are the leading cause of death and disability in the world as well as 80% of healthcare spending in the United States. Inherently, obstetric care provides a window into healthcare and the healthcare system where we would not have access to these patients otherwise. Specifically, the referrals involve connecting women to registered dietitians on staff, recruiting them to the health and fitness center, as well as sports medicine and physical therapy when appropriate. The psycho-social components including but are not limited to social relationships, stress, avoidance of risky substances, and trauma are under the direction of a social worker and/or Psych D. Furthermore, making use of already existing free services through the Alberto Culver Health Learning Center such as a new mom support group already existing in connection with Lake Forest Hospital.

Conclusions: Capturing women during a time of their lives where there is an innate investment in their health and well-being to help them control and hopefully reverse their trends allows an opportunity to get them to a point of a healthy lifestyle. This in turn has long term on their family’s health, lifestyle, and well-being. It takes only a few LM questionnaires during the first trimester to potentially initiate life-changing referrals, with the goal of identifying their social determinants of health, we are better able to protect, promote, and restore their health through existing dietary services, community resources, as well as other medical-related programs to use our existing resources more effectively and providing add on offerings with limited impact on operational bandwidth. This is imperative as social determinants of health are known to play a role in health outcomes and thus the need to provide precision medicine to an already in need population.

Michael D. Shapiro,1 Tariq M. Haddad,2,3 Howard S. Weintraub,4 Seth J. Baum,5 Khaled Abdul Nour,6 Wess Boatwright,7 Auris Browne,7 Imran Ayaz,7 Christie M. Ballantyne,8
1. Section on Cardiovascular Medicine, Center for Prevention of Cardiovascular Disease, Wake Forest University School of Medicine, Winston-Salem, NC, USA
2. Virginia Heart, Falls Church, VA, USA
3. Inova Heart and Vascular Institute, Falls Church, VA, USA;
4. New York University Grossman School of Medicine, New York University Center for the Prevention of Cardiovascular Disease, NY, USA;
5. Flourish Research, Boca Raton, FL, USA
6. Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI, USA
7. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA
8. Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

Purpose: Elevated lipoprotein(a) [Lp(a)] is the most common inherited dyslipidemia leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). Several cohort studies have reported elevated Lp(a) prevalence in the general population; however, there is a paucity of data in those with established ASCVD. This sub-analysis of the Lp(a)HERITAGE study (NCT03887520) assessed Lp(a) levels in United States (US) participants with ASCVD, stratified by race, ethnicity, and sex.

Methods: This cross-sectional study assessed the prevalence of elevated Lp(a) in adult participants (18–80 years of age) with a history of myocardial infarction or ischemic stroke ≥3 months to ≤10 years prior to enrolment (April 2019–July 2021) or symptomatic peripheral artery disease, across 192 US sites. Lp(a) and low-density lipid-cholesterol (LDL-C) levels were obtained using US central laboratory or historical data.

Results: In total, 8,295 US participants were enrolled. The sub-analysis included 7,679 participants with Lp(a) measured in nmol/L, of which 66.4% were male, 80.5% were White, 16.9% were Black, and 8.0% had Hispanic ethnicity. Compared with the overall population, median Lp(a) was >2.5-fold higher in Black participants (132.0 vs 52.1 nmol/L) and was 21.8% lower in Hispanic participants (40.7 vs 52.1 nmol/L); in females, median Lp(a) levels were >1.5-fold higher than in male participants (69.4 vs 45.6 nmol/L). Overall, 33.3% of participants had Lp(a) ≥125 nmol/L. Prevalence of Lp(a) ≥125 nmol/L was highest among Black participants (52.0%) and lowest among Hispanic participants (25.6%); a greater proportion of females had Lp(a) ≥125 nmol/L compared with males (38.9% vs 30.4%).

Conclusions: In the Lp(a)HERITAGE study, 33.3% of US participants with established ASCVD had Lp(a) levels ≥125 nmol/L. Compared with the overall population, the proportion of patients with Lp(a) ≥125 nmol/L was higher in Black (52.0%) and female (38.9%) participants and was lower in Hispanic participants (25.6%). These findings support more aggressive Lp(a) screening strategies among patients with established ASCVD, particularly female or Black patients. Furthermore, elevated Lp(a) levels can be used to inform the intensification of lifestyle and other risk factor management in clinical practice and may have implications for potential future therapies targeting Lp(a).

Deepak L Bhatt,1 Arun J Sanyal,2 Stephen A Harrison,3 Millie Gottwald,4 Shibao Feng,4 Germaine D Agollah,4 Cynthia L Hartsfield,4 Hank Mansbach,4 Maya Margalit,5 Rohit Loomba,6
1. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY
2. Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA
3. Pinnacle Clinical Research, San Antonio, TX
4. 89bio, San Francisco, CA
5. 89bio, Rehovot, Israel
6. NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA

Purpose: Non-alcoholic steatohepatitis (NASH) is characterized by excess hepatic fat accumulation, inflammation and cellular injury, with or without the presence of fibrosis. Fibroblast growth factor 21 (FGF21) regulates lipid and glucose metabolism and energy expenditure with potential benefit across a spectrum of metabolic diseases. Pegozafermin (PGZ) is a long acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) analog of FGF21 in development for the treatment of non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. This Phase 2b study evaluated the efficacy and safety of PGZ given weekly (QW) or every two-weeks (Q2W) versus placebo on histologic parameters in NASH patients with biopsy proven F2/F3 fibrosis.

Methods: This multicenter, randomized, placebo-controlled, double-blind trial randomized patients to PGZ 15mg or 30mg weekly or 44mg once every two weeks or placebo (weekly or every 2 weeks) for 24 weeks. Randomization was stratified by T2DM status and fibrosis stage (F2 vs F3). The two primary endpoints were the proportion of patients achieving either: 1) improvement of fibrosis by ≥1 stage with no worsening of NASH or 2) resolution of NASH without worsening of fibrosis. Initially, biopsies were assessed by one central pathologist. However, advances in methodologic approaches to consensus reading led to an amendment where biopsies were independently interpreted by 3 readers, blinded to timing, with a pre-specified algorithm used to generate a consensus score. If the 3 readers did not agree, the mode score was used; if that failed, then the median score was used. All baseline biopsies were reread by the panel. Key secondary endpoints included additional liver histology measures, changes in liver fat content (LFC) by magnetic resonance imaging proton density fat fraction (MRI-PDFF), fibrosis and inflammatory markers, metabolic effects, safety, and tolerability. A placebo-controlled, single-blind, 24-week extension study is ongoing under the same protocol.

Results: Of the 222 patients who had undergone randomization, 27 were excluded when the consensus-panel read did not qualify them based on the trial defined histologic inclusion criteria including 14 patients deemed to have Stage F4 fibrosis. Additionally, 3 patients who underwent randomization did not receive any PGZ or placebo which generated a full analysis population (F2 or F3 and NAS ≥4) of 192 patients randomized to PGZ 15mg QW (n=14), 30mg QW (n=66), 44 mg Q2W (n=51) or placebo (n=61). Mean baseline characteristics for the randomized analysis population (n=222) were age 56 years, 61% female, BMI 37 kg/m2, 66% T2D and 60% with F3 fibrosis. Full agreement or mode determined 91% to 99% of the final biopsy scores. The percentage of patients who met the criteria for fibrosis improvement without worsening of NASH was 7%, 22%, 26% and 27% for placebo, PGZ 15mg QW (p=0.10), 30mg QW (p=0.009), and PGZ 44mg Q2W (p=0.008) groups respectively. Similar results were observed for NASH resolution without worsening of fibrosis [2% PBO, 37% PGZ 15mg, 23% PGZ 30mg, and 26% 44mg Q2W; all p values <0.001]. PGZ treatment significantly improved NAS score by ≥ 2 points, LFC, non-invasive markers of hepatic inflammation and fibrosis with meaningful changes in lipids and HbA1c. Fibrosis improvement without worsening of NASH was also observed in 45% of patients with F4 fibrosis at baseline. PGZ was generally safe and well tolerated with the most common treatment emergent adverse events (TEAEs) being mild/moderate nausea and diarrhea and injection site erythema. No deaths occurred; six early terminations for TEAEs including one drug-related serious AE occurred. There were no occurrences of liver injury or tremor reported in any trial patient.

Conclusions: In this trial, treatment with the FGF21 analogue pegozafermin at doses of 30mg once weekly and 44mg every two weeks for 24 weeks led to significant improvements in fibrosis without worsening of NASH compared to placebo. Additionally, PGZ treatment provided additional benefit regarding NASH resolution without worsening of fibrosis. Improvement in both steatohepatitis and fibrosis indicates that PGZ may affect key aspects of the pathophysiology of NASH. Corroboration of biopsy findings by a variety of non-invasive tests further increases confidence in these histologic findings. PGZ is the first therapy to achieve fibrosis regression and NASH resolution with a Q2W dosing regimen. These robust Phase 2b results support advancing PGZ into phase 3 development. 

Ernst J. Schaefer, Masumi Ai, Joi A. Gleason, Ching-Ti Liu, Michael L. Dansinger

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston MA, USA;
Tufts University School of Medicine, Boston MA, USA; Boston Heart Diagnostics, Framingham MA, USA;
Tokyo Medical and Dental University Hospital, Tokyo, Japan;
Boston University School of Public Health, Boston MA, USA;
Tufts Medical Center, Boston MA, USA

Purpose: Diabetes mellitus is a major cause of morbidity and mortality. Diabetes is also a major cause of cardiovascular disease, kidney failure, neuropathy, and blindness. Type 2 diabetes is known to be associated with both insulin resistance and an inability to keep up with insulin demand by failing beta cells in the pancreas. Lifestyle change under controlled circumstances has clearly been shown to decrease diabetes risk and to facilitate conversion to non-diabetic status. Our purpose in these studies was to develop a diabetes risk prediction model and apply it to a large population along with lifestyle change, as well as to examine insulin homeostasis in normal, prediabetic, and diabetic subjects.

Methods: In 2,414 fasting male and female participants in the Framingham Offspring Study (mean age 58 years), free of diabetes at baseline, serum glucose, adiponectin, insulin, C-peptide, glycated serum albumin, total cholesterol, triglycerides (TG), direct low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were measured using automated standardized assays, and body mass index (BMI), parental history of diabetes, blood pressure, and cholesterol-lowering medication use were assessed. They were followed for 9.9 years for diabetes development. Using step-wise multivariate analysis, a diabetes risk model was developed and applied to a large fasting population (n=133,764) along with lifestyle modification.  These same biochemical measures were also measured in the large population. Homeostasis model assessment of insulin resistance (HOMA-IR) and production (HOMA-β) parameters were calculated in all subjects and related to diabetic status.

Results: In the Framingham Offspring Study, fasting glucose, BMI, log adiponectin, % log glycated albumin, parental diabetes, TG, and use of cholesterol-lowering medications entered the model (C statistic 0.924 for all parameters, 0.898 for biochemical variables, and 0.876 for glucose only, all P<0.0001). Surprisingly, neither insulin levels, HOMA-IR or HOMA-β entered the prediction model. In the large population of 133,764 test subjects, 56.3% were normal (fasting glucose <100 mg/dL), 36.2% were prediabetic (fasting 100-125 mg/dL), and 7.5% were diabetic (fasting glucose =/>126 mg/dL), with predicted 10-year diabetes risk rates of 0.3%, 5.5%, and 100.0% based on the biochemical model, respectively. All prediabetic and diabetic subjects were offered a free on-line personalized lifestyle intervention program meeting American Heart Association and DASH diet guidelines. Of 9,738 prediabetics that had follow-up assessments 6-12 months after their initial assessment, only 12.0% (1,169 subjects) opted to enroll and receive a personalized life-plan based on their dietary preferences. Their 10-year diabetes risk based on the biochemical model decreased from 5.7% to 3.1% (-46%) versus no change (0.0%) in prediabetic control subjects (n=8,569), (P<0.0001). Of 2,017 diabetic subjects that had a follow-up evaluation 6-12 months after their initial assessment, only 10.7% (n=216) opted to enroll and receive a personalized life plan; 8.2% were no longer diabetic after lifestyle change versus 3.4% in the diabetic control subjects (n-1,801) (P<0.0001). Lifestyle change was effective in decreasing insulin resistance (P<0.0001), with no significant effect on insulin production. Moreover, lifestyle change was most effective in promoting weight loss in prediabetic and diabetic subjects that had marked insulin resistance. HOMA assessments showed that some diabetic subjects had markedly decreased insulin production, indicating a potential need for insulin therapy.

Conclusions: Our data are consistent with the following conclusions: 1) Diabetes risk can be very accurately predicted using a full model, a biochemical parameter only model, and even a model with fasting glucose alone; 2) HOMA assessment was found to be valuable in assessing which prediabetic and diabetic subjects might lose the most weight with lifestyle change, and also which diabetic subjects might need insulin therapy because of decreased insulin production; 3)  Lifestyle change significantly lowered diabetes risk in prediabetic patients and was able to convert diabetics to non-diabetic status in a subset of diabetic patients; and 4) Lifestyle change therapy is under-utilized in the prediabetic and diabetic population.

Shawn Riser Taylor, PharmD, CPP, CDCES,1 Ana But-Gusaim, PharmD Candidate,1 Darius Bryant, PharmD Candidate,1
1. Wingate University School of Pharmacy

Purpose: Evidence has shown the integration of clinical pharmacist practitioners (CPPs) positively influence patient outcomes in chronic disease management. Presently, there is limited data to ascertain why the addition of CPPs in the primary care team improves patient outcomes.

Methods: The objective of this study is to investigate if the integration of CPPs in primary care influences guideline-based pharmacological therapy for the management of diabetes mellitus (DM). The secondary objective is to evaluate if achievement of quality metrics pertaining to diabetes.  Retrospective data was collected and analyzed between two groups, the integrated group with CPP and the non-integrated group without CPP. Descriptive statistics and Chi-square tests were utilized for data analysis.

Results: One-thousand six hundred and thirteen patients diagnosed with type 2 diabetes were included in the analysis. Of this population, 46% (n=508) were in the integrated group with a CPP.  In patients with uncontrolled diabetes and no contradiction or previous intolerance, patients were more likely to not be on the guideline-recommended metformin therapy in the non-integrated group compared to the integrated group (16% versus 7.2%, respectively, p<0.05).  In patients with risk of hypoglycemia, patients in the integrated group were more likely to be prescribed glucagon compared to the non-integrated group, respectively (16% versus 0.7%, p<0.05).  There was no significant difference in use of sulfonylureas between groups. In regards to quality metrics of hemoglobin A1c and diabetes complication screenings (retinal eye exam, foot exam and nephropathy), all were more likely to be achieved in the integrated group compared to the non-integrated group.

Conclusions: Integration of CPPs in the management of diabetes was found to significantly improve adherence to guidelines compared to the  non-integrated group in a primary care setting. Additionally, achievement of quality metrics was optimized in the integrated group. 

Maxine Lang,1 Marianna Fernandes,1 Margaret R. Diffenderfer,1 Lihong He,1 Ernst J. Schaefer,1
1. Boston Heart Diagnostics, Framingham MA, USA

Purpose: Cardiovascular disease (CVD) risk assessment in the laboratory entails not only the measurement of fasting serum cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C); but also in our view many additional biomarkers – direct low density lipoprotein cholesterol (LDL-C), direct small dense low density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) or Lp(a), apolipoprotein B (apoB), high sensitivity C-reactive protein (hs-CRP), glucose, glycosylated hemoglobin (HbA1c), homocysteine, folate, vitamin B12, creatinine, thyroid stimulating hormone (TSH), uric acid, and omega-3 fatty acids (specifically eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) – as well as various genetic variants that are associated with increased CVD risk (APOE, MTHFR, FV or Factor V Leiden, F2 or Prothrombin variant, SLCO1B1 [statin myopathy risk], 4Q25 [atrial fibrillation risk], and LPA [Lp(a), CVD risk, correctable with aspirin]). In addition, phlebotomy services have become increasingly costly and are sometimes unavailable for patients. Our purpose in this study was to develop and validate dried blood spot (DBS) analyses for these various parameters after fingerstick sampling.

Methods: Using McKesson #17 blade lancets for fingerstick sampling, 249 fasting volunteers placed 4-6 drops of capillary blood on ADX-100 cards (Advance Dx, after an overnight fast. They also simultaneously underwent phlebotomy. Cards were dried at room temperature for at least 30 minutes, then sealed, and tested for up to 14 days after sampling; punches from the serum and red blood cell areas of the cards were obtained, solubilized, and analyzed. CVD risk markers were measured using Beckman AU480 and Beckman ACCESS analyzers; fatty acids were measured by gas chromatography/mass spectrometry after lipid extraction; and genotyping was carried out at the following gene loci: APOE, MTHFR, FV, F2, SLCO1B1, 4Q25, and LPA.

Results: The following DBS measurements were very highly and significantly correlated (Pearson) with standard venipuncture results (r≥95%; P<0.00001): total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, Lp(a), hs-CRP, creatinine, glucose, HbA1c, TSH, and uric acid. ApoB, lipoprotein-associated phospholipase A2, creatinine, homocysteine, folate, vitamin B12, vitamin D, and uric acid were also highly and significantly correlated (r >90%; P<0.0001). The following fatty acids were well correlated with phlebotomy results at >0.90 (P<0.0001): EPA, DHA, arachidonic acid, omega-3 index, omega-6 index, and monounsaturated fat index. This was not the case for saturated or trans fatty acids. All genotyping was 100% correlated when comparing DBS and phlebotomy testing results.

Conclusions: Dried blood spot testing is an effective and reliable method for advanced CVD risk assessment and management, measuring multiple parameters as outlined above. Moreover, dried blood spot card sampling does not require phlebotomy, ultracentrifugation, or shipping by overnight courier on frozen ice packs, substantially reducing processing costs.

Jorge Plutzky, MD,1 Danielle Brennan, MS, Na Li, PhD,2 LeAnne Bloedon, MS,3 Paula Robinson, MS,3 Maggie Horner, MBA,3 JoAnne Foody, MD,3 Stephen J Nicholls, MBBS, PhD,4
Steven E Nissen, MD,2 A. Michael Lincoff, MD,2
1. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
2. Cleveland Clinic, Cleveland, OH
3. Esperion Therapeutics, Inc. Ann Arbor, MI
4. Victorian Heart Institute, Monash University, Melbourne, VIC, Australia

Purpose: Global guidelines uniformly recommend reducing LDL cholesterol (LDL-C) to reduce cardiovascular (CV) risk in patients with atherosclerotic CV disease (ASCVD, secondary prevention) or at high risk for a first major CV event (primary prevention). However, hypercholesterolemia is often untreated or undertreated. Statin intolerance, typically manifesting as myalgia, is a major contributor to inadequate LDL-C control involving multiple barriers. Minimal data exist for overcoming statin intolerance in large, prospective clinical CV trials. Appropriate LDL-C management is a particular issue among primary prevention patients, including women and those with diabetes, despite inherent, significant opportunities for improving clinical outcomes in such patients. Moreover, clinical trials for LDL-C lowering in primary prevention were conducted years ago, suggesting possible outdated guidance, further fueling questions some have raised whether cholesterol lowering benefits exceed potential harms in primary prevention patients. Additional therapeutic options and clinical CV outcome trial data are needed for high risk secondary and primary CV prevention patients with statin intolerance, and such strategies have potential broad relevance. In the CLEAR Outcomes trial, 13,970 high CV risk secondary and primary patients unable or unwilling to tolerate guideline-recommended statin doses were randomized to either bempedoic acid (BA), an orally administered inhibitor of ATP citrate lyase (ACL), or placebo, and CV outcomes assessed. The effect of BA on CV outcomes in the 30.1% (4206) of primary prevention patients have been previously presented.

Methods: CLEAR Outcomes was a double-blind, randomized, placebo controlled cardiovascular outcomes trial of BA 180 mg oral daily compared with placebo in a mixed population of primary and secondary prevention patients unable or unwilling to take guideline recommended doses of statins. The primary end point was a composite of death from CV causes, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization. A prespecified analysis was performed in the primary prevention patients meeting high CV risk criteria: 1) Reynolds Risk Score >30% or a SCORE risk score >7.5% over 10 years, 2) Coronary artery calcium score > 400 Agatston units or 3) Type 1 or Type 2 Diabetes in women > 65 years or men > 60 years.

Results: In the primary CLEAR Outcomes report, patients randomized to BA (N = 6992) had a greater reduction in LDL-C compared to placebo (N=6978) (-29.2 mg/dL placebo corrected change from a baseline mean value of 139.0 mg/dL), and lower risk of the primary CV endpoint [11.7% vs. 13.3%; hazard ratio (HR), 0.87; 95% CI 0.79-0.96], composite of cardiovascular death, nonfatal stroke, or nonfatal MI (8.2% vs. 9.5%; HR, 0.85; 95% CI 0.76-0.96); fatal or nonfatal MI (3.7% vs. 4.8%; HR, 0.77; 95% CI 0.66-0.91); and coronary revascularization (6.2% vs. 7.6%; HR, 0.81; 95% CI 0.72-0.92). Compared to placebo, BA also reduced C-reactive protein levels by 21.5% (median baseline of 2.3 mg/dL). Among the 30.1% (4206) primary prevention enrollees, the mean age was 68 years, 59% were female, and 66% had diabetes. Over a median duration of follow-up of 39.9 months, BA was associated with a significant reduction in the primary end point (5.3% vs 7.6% events; adjusted HR, 0.70; 95% CI 0.55-0.89) and secondary end points, including the composite of CV death, MI, or stroke (4.0% vs 6.4%; adjusted HR, 0.64; 95% CI 0.48-0.84); fatal or non-fatal MI (1.4% vs 2.2%; adjusted HR, 0.61; 95%CI 0.39-0.98); CV death (1.8% vs 3.1%; adjusted HR, 0.61; 95% CI 0.41-0.92); and all-cause mortality (3.6% vs 5.2%; adjusted HR, 0.73; 95% CI 0.54-0.98). Despite enrolling only patients with reported statin intolerance, BA was similarly tolerated as placebo (treatment discontinuation rate BA 29.1% vs placebo 31.7%). Gout and cholelithiasis occurred more in those receiving BA than placebo (3.1% vs. 2.1%; 2.2% vs. 1.2%, respectively); modest increases in serum creatinine, uric acid, and hepatic-enzyme levels were also seen.

Conclusions: The ACL inhibitor bempedoic acid, as compared to placebo, significantly lowers LDL-C and decreases major CV events in high-risk patients with statin intolerance and in need of either secondary or primary prevention of ASCVD. Bempedoic acid is now established as an important addition to the armamentarium for LDL-C lowering and CV risk reduction.

Faiz Alam, Shivani A. Patel, Mohammed K. Ali, Romaina Iqbal

School of Medicine, Emory University, Atlanta, Georgia, United States of America
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America
Department of Family and Preventive Medicine, School of Medicine, Emory University, Atlanta, Georgia, United States of America
Global Diabetes Research Center, Woodruff Health Sciences Center, Emory University, Atlanta, Georgia, United States of America
Department of Community Health Sciences, Aga Khan University, Karachi, Sindh, Pakistan

Purpose: There is a growing body of literature focusing on the concordance within households of cardiometabolic risk factors in Asia. This includes concordance between parent-child, sibling, spousal dyads, and between any co-residing members of households.
For Pakistan, there is a lack of published data regarding concordance of cardiometabolic risk and factors that can influence the degree of concordance. Additionally, Pakistan has an average household size of 6.8, one of the highest averages in the world. 55% of households are multigenerational and 33% are three generation households, with 49% of all households having cohabiting extended family members. Therefore, intergenerational influences on health may be particularly salient in this setting. There is a need to better understand relationships between household members, especially in a region where there is interaction between multiple variations of individual relationships in a shared environment.

The CONcordance of Cardiometabolic Diseases and Risk Factors (CONCAR) in Pakistani Households Study is a cross-sectional study with data collection taking place in Karachi, Pakistan. Data collection was done in a subset of households within clusters that have been established by the ongoing Cardiometabolic Risk Reduction Strategies in South Asia (CARRS) Cohort Study. The purpose of this study was to assess the association between the presence of adults with hypertension or overweight status (BMI > 25) and the blood pressure and weight status of children within the same household.

Methods: CONCAR data collection took place from March to June of 2023 by trained field workers who collected information on demographics, immediate, behavioral, and social risk factors and disease history of cardiometabolic disease, anthropometry, and blood pressure. Inclusion criteria were members of an established CARRS household who are 8 years and older. Pregnant women and those who cannot recall their behavior over the past year, such as those with dementia, were excluded.
Data analysis included descriptive statistics including demographics, average household size, percent overweight, percent hypertensive adults, average BMI-for-age z-score of children (BAZ) using the WHO Growth Reference, and average systolic blood pressure for children. Linear regression was done to analyze associations between 1) presence of hypertension among any household adult and the average systolic blood pressure of children (ages 8-17), and 2) presence of overweight among any household adult and the BAZ of children, controlled for household income and sex of child.

Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg when averaged between two readings (a third reading was taken if the difference between first two systolic was >10 or diastolic was >6). BMI and BAZ were calculated using weight and height measurements taken during the visit. Data was treated as outliers if the adult BMI was <12 or >60 or if the child BAZ was <-5 or >5. Statistical significance was determined using p <0.05. Data was collected via the REDCap mobile application and analyzed using SPSS v29.0.0.0.

Results: The CONCAR Cohort included 1508 participants from 352 households. 158 of these households had at least one child < 18 years, with 916 total participants in the analyzed sample, including 327 children. After removing outliers, the analyzed sample included 904 participants, with 316 children, with an average household size of 5.7. The average age of adults was 40.5 years and of children was 12.6 years. 40.1% of adults and 50.5% of children were male.

20.3% of adults have hypertension, with 50.6% of households having at least one adult with hypertension. 51.4% of adults are overweight, with 82.6% of households having at least one adult who is overweight. Among children, average systolic blood pressure is 104.45 +/- 12.55 and the average BAZ is -0.74 +/- 1.60.

The regression analyses showed a positive association between presence of at least one adult with hypertension and child systolic blood pressure (β = 0.142, p = 0.007) and between presence of at least one adult who is overweight and child BAZ (β = 0.155, p = 0.006) even when controlling for household income and sex of child.

Conclusions: Adult hypertension was associated with higher systolic blood pressure in children and adult overweight status was associated with higher BAZ in children within the same household. These findings further strengthen the case for intergenerational transmissibility of cardio-metabolic risks, and how these relations relate between adults and children within the household. From a primary care and primary prevention perspective, noting the disease state and risk factor status of adults in the household may inform preventive care for children in the household.

Saurabhi Samant, MD,1 Mustafa Al-Taei, MD,1 Katherine E. Di Palo, PharmD, MBA, MS, FHFSA, FAHA,1,2
1. Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine
2. Office of Medical Affairs Montefiore Medical Center Bronx, NY

Purpose: Iron deficiency (ID), independent of anemia, is a prevalent comorbidity in heart failure and is associated with impaired functionalcapacity, lower quality of life, and increased frequency of hospitalizations, particularly in patients with heart failure with reduced ejection fraction(HFrEF). This study sought to determine the screening and treatment rates of ID in individuals with acute decompensated heart failure (ADHF).

Methods: Using claims data, we identified hospital encounters in adults older than 18 years of age admitted for ADHF with EF <40% between December 2022 to June 2023 at a Community Hospital in the Bronx, NY. ID was defined per guidelines on HF as serum ferritin <100 ng/mL or when100-299 ng/mL, a transferrin saturation (TSAT) <20%. The data was examined using univariate analysis.

Results: There were 106 total hospital encounters for ADHF with 100 unique patients. Seventy percent (n=75) were male, 60% non-Hispanic Black, followed by Hispanics (32%). ID was not screened in 67% (n=71) of eligible encounters. ID was identified in 51% (n=18) of patients, and 14% (n=5) received intravenous (IV) iron infusion; however, none received the appropriate dosage with a mean dose of 160 mg.

Conclusions: In a multi-ethnic, underrepresented, and underserved/target population with a significant disease burden admitted with ADHF, ID screening was underused. Most patients with ID did not receive IV iron supplementation and/or were underdosed. Larger quality improvement studies are needed to create strategies for implementing ID screening /treatment and particularly improve physician inertia.

Olanrewaju D. Eniade,1,2,3,4 Adewemimo, Olaosebikan,1,2 Abayomi T. Olarinmoye,3 Tondiyen L. Jasper,4
1. International Foundation Against Infectious Disease in Nigeria
2. Epidemiology and Medical Statistics Department, University of Ibadan, Nigeria
3. Adeleke University, Ede, Nigeria
4. Institute of Human Virology, Nigeria

Purpose: Childhood obesity is a significant public health concern with far-reaching implications for the well-being of individuals and societies (Caprio et al., 2020). Some studies reported that mothers play a central role in shaping their child’s early development, and thus, their profile and health characteristics can have a profound impact (Shrestha et al., 2021).  In the context of sub-Saharan Africa, where healthcare resources are often limited, understanding the multifaceted factors contributing to childhood obesity becomes crucial. Hence, this study delves into a particular facet of this issue, focusing on the influence of maternal characteristics on childhood obesity among under-five (6-59months) children in selected SSA countries.

Methods: A secondary analysis was conducted on data from the Demographic and Health Survey (DHS) representing seven carefully chosen sub-Saharan African (SSA) countries, namely Nigeria (20%), Mauritania (18%), Liberia (5%), Kenya (32%), Gambia (7%), Gabon (10%), and Cameroon (8%). The selection criteria encompassed countries with recent DHS data (≥ 2018) and a maternal obesity rate exceeding or equal to 10%. To maintain a focus on children beyond the immediate postpartum period, women who had given birth within the preceding six months of the DHS survey were excluded from this analysis. The outcome variable was childhood obesity derived using the WHO Body Mass Index (BMI) Standard Deviation (SD) for children and categorized as “Obese” (WHO BMI SD≥ 171)   or “Not Obese” (WHO BMI SD<171). The key explanatory variable of interest was maternal obesity categorized as “Obese” (BMI ≥ 30)   or “Not Obese” (BMI <30) (WHO, 2017). Additionally, various demographic, socio-economic, and household factors pertaining to the mothers were considered as potential explanatory variables.
We presented a descriptive overview of the data, utilizing measures such as means, frequencies, and percentage distributions. Subsequently, bivariate analysis was performed employing the Chi-Square test of independence to explore associations between variables. For a more comprehensive examination of the factors influencing childhood obesity, a binary logistic regression was conducted during the multivariate analysis. To establish statistical significance, variables were considered statistically significant at a p-value of less than 5%. All analyses were carried out using Stata MP 17.

Results: The mean age of mothers in the study was 33.1 ± 6.0 SD years while the mean age of the children was 11.2 ±3.9 SD months. Out of the total children, 12,149 (49.3%) were female, and 14,774 (59.9%) lived in rural areas. The prevalence of obesity, overweight, and underweight among the children were 5.3%, 10.1%, and 5.4%, respectively. Among the mothers, 1,417 (8.0%) were underweight, 8,980 (50.8%) had a healthy weight, 4,259 (24.1%) were overweight, and 3,012 (17.1%) were obese. The prevalence of obesity did not significantly differ between male (5.4%) and female (5.7%) children, with a p-value of 0.450.
The multivariate analysis revealed that children whose mothers were underweight (OR: 0.37, 95%CI= 0.25 – 0.54) were less likely to be obese, while children whose mothers were Overweight (OR: 1.45, 95%CI=1.25- 1.69), and Obese (OR:1.59, 95%CI=1.34 – 1.89)  had a higher likelihood of  being obese compared to children whose mothers had a healthy weight. Also, mothers’ with low exposure to media (OR:0.67, 95%CI= 0.57– 0.78) and high media exposure (OR:0.57, 95%CI=0.44 – 0.74) had a protective effect against childhood obesity compared to those with no media exposure. Also, we found that the risk of childhood obesity was higher (OR: 1.26, 95% CI = 1.11 – 1.44) among children whose mothers were engaged in work compared to mothers who were not working.

Conclusions: This study revealed that one out of twenty children had obesity in sub-Saharan Africa. In combating childhood obesity, our findings suggest that maternal weight, media exposure, and maternal employment status are important factors associated with childhood obesity.
The influence of mothers’ weight on childhood obesity suggests a connection between a mother’s and child’s health habits. Also, media exposure significantly influences obesity which suggest a link between media exposure, children’s food choices and activity levels. In addition, there may be a connection between mother’s employment status, the time, and resources available for preparing healthy meals and engaging in physical activities with their children.
These findings provide valuable insights for interventions aimed at reducing childhood obesity in the region. Tailored strategies that address these factors and focus on at-risk groups, as identified in our study, will be essential in promoting healthier lifestyles and countering the rising trend of childhood obesity in sub-Saharan Africa.

AG Palladino-Davis,1 Matthew J. O’Brien,1 Anthony J. Pick,1
1. Northwestern University

Purpose: The COVID-19 pandemic forced a new approach to patient care and inherently health education. Immigrants, refugees, and the underserved were impacted in unprecedented ways whereby clinics they relied on for their care were now faced with furloughs and closures. Such was the case with a public clinic in the Chicago metropolitan area in which the Diabetes PreventionProgram (DPP) was no longer available. The loss of this particular DPP cohort meant leaving orphan a group of post-menopausal women after having received a diagnosis of metabolic syndrome.

Methods: With a duty to protect, promote, and restore people’s health we established and recruited underserved Hispanic women directly from these clinics who would otherwise not have access to lifestyle medicine interventions and thus the possibility to create a dent on their cardiometabolic health.

Results: This initiative demonstrates that despite losses and closures, a healthcare system still managed to reinvent current strategies in order to ensure these women would not be left without the health education they were in dire need of. We demonstrated an ability to use existing programs to still deliver quality of care despite COVID-19 related closures. This was accomplished by administering health education strategies‚ interventions and programs, chronic disease management and prevention. Importantly public health theories and concepts applied to clinical medicine allowed for social determinants of health of this vulnerable population to be the direct driving force as to how the program was individualized. This allowed us to provide as much precision as possible with the health literacy of the population and hopefully increase the sustainability of their lifestyle changes in the long-term.

Conclusions: Bearing in mind that social determinants of health have a profound impact on the lives and health of individuals, we sought to take advantage of this at-risk population who openly welcomed support and did a great job adapting. Metabolic syndrome can create changes at the epigenetic level; however, lifestyle medicine approaches are also known to potentially alter these changes back to intended homeostasis. At its foundation, our modified DPP intended to educate participants on preventing or delaying type 2 diabetes, maintaining a healthy weight, and education focused on cardiovascular disease. This is important as chronic conditions are the leading cause of death and disability worldwide as well as 80% of healthcare spending in the United States, and diabetes is at the genesis of this domino effect. Reinventing health education strategies with currently available programs within the healthcare system allowed for the often forgotten underserved population to continue to get the care they need and deserve and hopefully narrow the gap of disparities and consequently health inequities.

Manu Chakravarthy,1 Federico A. Argüelles-Tello,2 Ana Liza A. Sun,3 Michael Elliott,1 Luis Acosta,1 Jonathon E. Rankin,4 Stig K. Hansen,1
1. Carmot Therapeutics, Berkeley, CA, USA
2. Avante-Sante Research Center, San Pedro Garza García, Mexico
3. Linear Clinical Research, Perth, Australia
4. Syneos Health, Adelaide, Australia

Purpose: GLP-1 and GIP can deliver complementary pharmacology when combined. CT-388 is a biased dual GLP-1 and GIP receptor modulator that exhibits no to minimal β-arrestin coupling at either receptor, designed for once-weekly subcutaneous administration. Primary objective was to investigate safety and tolerability of CT-388.

Methods:  A Phase 1, randomized, placebo-controlled, double-blind study was conducted where single ascending doses (0.5-7.5 mg) and multiple ascending doses (MAD; doses 5-12 mg via titration in 3 cohorts) for 4 weeks were administered to adults with overweight/obesity.

Results: A total of 64 participants [N=28 (men)/36 (women); median age=34 years; median BMI=33 kg/m2) received at least 1 dose of CT-388 or placebo. Pharmacokinetic profile was investigated over a wide dose range (0.5-12 mg) and supports once-weekly administration. Percent change in body weight from baseline at Day 29 was dose responsive and significantly greater in CT-388 treated participants versus placebo (p <0.0001) across the 3 MAD cohorts with placebo-adjusted Least Square Mean difference [95% CI] of -4.8% [-6.3, -3.3], -6.4% [-7.8, -5.0], and -8.5% [-10.4, -6.7]. Mean percent decrease from baseline at Day 23 in fasting glucose (↓8-10%), insulin (↓20-26%), HOMA-IR (↓26-33%), AUC0-120min glucose (↓26-28%) and AUC0-120min insulin (↓33-58%) during oral glucose tolerance tests were seen in cohorts dosed up to 12 mg of CT-388, suggestive of improved insulin sensitivity. Over the 4-week treatment period, CT-388 was generally well tolerated without any treatment-related discontinuations in the MAD cohorts. The most frequent side effects reported were gastrointestinal (decreased appetite, nausea, vomiting, diarrhea), which were mostly mild in severity.

Conclusions: In summary, CT-388 delivers clinically meaningful weight loss and metabolic control with a favorable tolerability profile. These data warrant further clinical evaluation of CT-388, possibly with minimal to no titration, for the treatment of obesity, T2DM, and other weight-related comorbidities.

Conference Venue


Sign up to receive updates on educational opportunities, complimentary content, exclusive discounts, and more.