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Obesity slowly undoing progress made in decreasing CVD

Obesity slowly undoing progress made in decreasing CVD

Although progress has been made in reducing BP and cholesterol in patients in the United States, obesity, a widespread condition, is halting that progress by increasing the risk for CVD. The prevalence of obesity has risen over the past 3 years, and more than one-third of U.S. adults are estimated to have obesity, according to a 2017 report from the National Forum for Heart Disease and Stroke Prevention. New data from the NHANES surveys showed that agestandardized prevalence of obesity among adults increased from 33.7% in 2007-2008 to 39.6% in 2015-2016. As obesity increases, medical expenditures for the treatment of obesity-related illnesses also rise. In a study published in Clinical Chemistry in 2018, medical expenditures in the United States increased by 29% from 2001 to 2015.
“Even though we’re able to make headway in those other risk factors which improve CVD rates, because we, as a society, have not done as great a job as addressing obesity and diabetes, then that’s going to halt the prevention,” Ian Neeland, MD, assistant professor of internal medicine at UT Southwestern Medical Center in Dallas and a Cardiology Today Next Gen Innovator, said in an interview. “It’s certainly one of the main drivers that needs to be further worked on.” Sidney C. Smith, Jr., MD, FAHA, FESC, FACP, MACC, professor of medicine in the division of cardiology at University of North Carolina School of Medicine in Chapel Hill and past president of the AHA and World Heart Federation, agreed.
“It’s felt that unless [obesity] can be thwarted, offset, successfully addressed, we have major problems on our hands in terms of heart attacks and strokes in the future from a cardiovascular standpoint,” he told Cardiology Today. Not only does the relationship between obesity and CVD affect adults, but the risk for CVD in patients with obesity starts in childhood and adolescence. Almost 21% of adolescents aged 12 years to 19 years are obese, and many of these children will continue to have obesity into adulthood, Sadiya S. Khan, MD, MSC, assistant professor of medicine and preventive medicine at Northwestern University School of Medicine, told Cardiology Today. “An understudied question of concern is, as children and adolescents are becoming obese at younger ages, is this burden of cardiovascular disease going to even increase in the coming years?” Khan said. “This further emphasizes the need for primordial prevention starting in childhood throughout adulthood to prevent development of obesity and obesity-related cardiovascular disease.”
The number of patients with CVD will most likely increase over the next decade, as there is a lag between the development of obesity and CVD. The lag may take between 10 years and 12 years, Cardiology Today Editorial Board Member Keith C. Ferdinand, MD, FACC, FAHA, professor of medicine at Tulane University School of Medicine in New Orleans, said in an interview. “This portends, perhaps in the future, with persistent hypertension, increase in new-onset diabetes, increase in overweight and obesity status that we will see perhaps an uptick in cardiovascular mortality going forward,” Ferdinand said.
Evidence of association
Numerous studies and analyses have established the relationship between obesity and CVD, even as CV-related mortality rates have decreased over time. In a study published in The New England Journal of Medicine in 2007, CHD-related deaths among men and women declined by almost half from 1980 through 2000, mainly due to secondary preventive therapies. In the same time period, diabetes-related deaths increased by 10% and those caused by an increased BMI increased by 8%. Other analyses of cohort-based studies of patients with obesity, including ARIC, CARDIA and the Framingham Heart Study, show a higher rate of stroke, CHD and HF among obese adults compared with those without obesity. Other conditions often linked with obesity include atrial fibrillation, sudden cardiac death, venous thromboembolism, pulmonary embolism and sleep apnea.
The increased prevalence of obesity in patients with CVD has affected lifespans in this patient population. In a study published in JAMA Cardiology in 2018, Khan and colleagues found that both men and women with overweight, obesity and morbid obesity had an increased risk for CVD compared with those with normal weight. Patients with obesity also had shorter longevity. Although the association has been recognized, the mechanisms underlying the association have yet to be determined. Relevant may be risk factors such as hypertension, dyslipidemia, diabetes and excess weight itself, experts told Cardiology Today.
“There is emerging evidence on obesity as an endocrinologic organ, and the inflammatory cytokines and substances that it secretes can injure the heart, therefore affecting the heart’s function and structure,” Neeland said. The location of fat can also be associated with CVD. Central obesity, when fat is located around the abdomen, can not only lead to diabetes, but can cause inflammation from the adipocytes of fat cells. HF is the most prominent condition associated with obesity, although its development is only partially explained by the CV risk factors linked to obesity. Some animal and mechanistic data suggest that obesity has a deleterious effect on the myocardium or is associated with hemodynamic changes. These changes may also be related to fat accumulation in the myocardium itself.
The connection between obesity and CVD may also be explained through mechanisms associated with inflammation, including elevated levels of TNF alpha, CRP, plasminogen activator inhibitor-1 and endothelial cell dysfunction. “That is an area of ongoing work that we don’t have 100% understanding of, but it’s certainly an important focus of investigation,” Chiadi E. Ndumele, MD, MHS, assistant professor of medicine at Johns Hopkins University, told Cardiology Today.
Furthermore, obesity is also associated with hypertension. The new American College of Cardiology/American Heart Association hypertension guideline published in November 2017 lowered the threshold for hypertension diagnosis to 130 mm Hg systolic BP/80 mm Hg diastolic BP, which will lead to more Americans receiving a diagnosis of hypertension, much of it driven by obesity. “As the guidelines for hypertension have become more rigorous, therefore, the need to control the increasing obesity rates in the United States will even be more potent because with lower diagnosis of hypertension at 130/80 mm Hg and above in adults, the rates of obesity will increase the rates of hypertension exponentially,” Ferdinand said.
The AHA also published a scientific statement in Circulation back in 2006, in which it recognized the relationship between obesity and stroke, CHD and congestive HF, but primarily described it through traditional CVD risk factors and did not emphasize the independent association between obesity and HF. The scientific statement is currently being updated with newer data, Ndumele said. In 2013, the AHA, ACC and The Obesity Society published prevention guidelines in Circulation on the management of overweight and obesity in adults. The guidelines recognize the association between obesity and CVD and how to properly treat those patients in hopes of achieving optimal CV health.

Importance of prevention
Cardiologists are often the last health care providers to address obesity prevention. Often, this topic is first broached with primary care physicians and/or endocrinologists. However, the cardiologist can play a special role in the opportunity to discuss secondary prevention with patients. “It’s never too late to work on obesity and healthy lifestyle management,” Neeland said. “There are cases where you can cure diabetes and hypertension just through lifestyle changes and weight loss. There’s certainly a lot of opportunity for cardiologists to make major changes in their patients’ lives by addressing obesity, preventing it and then treating it once it occurs.”
Focusing on lifestyle modifications in patients with obesity in the setting of CVD has been shown offer to health benefits, especially for CV risk factors. “I’m usually faced with a patient who is overweight and has CV risk factors that have developed,” Smith said. “I find myself not only treating the hypertension or the dyslipidemia — or if it’s gone even further, they’ve had their heart attack or developed diabetes — but also I am treating the associated risk with obesity, and trying to get the patient to lose weight. There, it becomes difficult depending on where the BMI is.”
In the Look AHEAD study published in The New England Journal of Medicine in 2013, 5,145 patients with overweight or obesity and type 2 diabetes were randomly assigned to participate in an intensive lifestyle intervention with increased physical activity and decreased caloric intake or diabetes support and education alone. The intervention group lost more weight than the control group at 1 year (8.6% vs. 0.7%) and at the end of the study (6% vs. 3.5%). Although the intervention group also had greater improvements in all CV risk factors and a greater reduction in glycated hemoglobin, rates of the primary outcome, which was a composite of nonfatal MI, CV-related death, nonfatal stroke or hospitalization for angina, were similar in both groups.
Although a goal of preventing obesity may seem obvious, it is not always discussed with patients. “We generally underperform with regard to addressing obesity with patients, and from providers with whom patients have a trusting relationship and where our medical recommendations have a lot of influence, it’s powerful for our patients to hear from us about the importance of a lifestyle changes and weight loss where appropriate,” Ndumele said. “At many institutions, there are resources often covered by insurance to support weight loss for patients. It’s a topic we can certainly address within our offices and something we can also utilize various resources to help with as well.”
Primordial prevention, which needs to occur before a patient is referred to a cardiologist, is an important approach not only for obesity, but also for the effects associated with it such as CVD. Family history of obesity is a marker for adverse lifestyle in patients, specifically high-calorie meals, sedentary status and potentially hidden genetic factors. “[Therapies] are expensive, and it’s my way of thinking the real approach to this lies in preventing obesity from starting,” Smith said. “The effective strategies there are associated with diet and exercise.”
Effective weight loss
Lifestyle intervention is the first step in treating patients with obesity, typically focused on increased physical activity and healthy nutrition. “Lifestyle is the most impactful strategy we have because it’s the cheapest, it’s the most effective and efficient, and it has very little risk,” Neeland said. Macronutrients and micronutrients are critical in changing eating habits while controlling the amount of daily caloric intake. A multidisciplinary approach to dietary lifestyle changes aids in its success. Involving a physician, a health coach and a nutritionist can also help with patient adherence. If a multidisciplinary approach is not available, patients can download free apps on their phones to help track reductions in calorie intake, increases in physical activity or food logs.
The AHA recommends that to improve overall CV health, people should have at least 30 minutes of moderate-intensity aerobic activity at least 5 days per week; or at least 25 minutes of vigorous aerobic activity at least 3 days per week; or a combination of moderate- and vigorous-intensity aerobic activity, as well as moderate to high-intensity muscle-strengthening activity at least 2 days per week for additional health benefits. It also recommends that to improve BP and cholesterol levels, people should have at least 40 minutes of moderate-to-vigorous physical activity three or four times per week.
When lifestyle interventions are not effective for a 5% to 10% reduction of body weight, the next strategy is pharmacologic therapy. Currently there are five FDA-approved medications for weight loss: phentermine/ topiramate (Qsymia, Vivus), liraglutide (Saxenda, Novo Nordisk), lorcaserin, (Belviq, Eisai), naltrexone bupropion (Contrave, Orexigen) and orlistat (Alli, GlaxoSmithKline). Although these medications are effective, they do have some side effects and potential risks, so they should serve as aids to lifestyle changes and not be a standalone treatment, experts said. Some side effects include nausea, vomiting, insomnia, headache and pancreatitis. The medications also have contraindications such as pregnancy, multiple drug interactions, drug or alcohol withdrawal and medullary thyroid cancer, Neeland said. “The take-home message therefore is not only do we need prevention, but in those patients who manifest risk reduction, they should be aware of the benefits of modern pharmacotherapy including antihypertensive agents, statins control of dysglycemia, especially with some of the newer diabetic medications such as the GLP-1 agonists and the SGLT2 inhibitors, agents which have been shown in some recent trials to have cardiovascular benefit,” Ferdinand said.
The most effective therapy for obesity is bariatric weight-loss surgery, which is reserved for patients at extremely high risk for comorbidities or those who did not lose a substantial amount of weight with lifestyle changes and pharmacotherapy. In a study published in JAMA in January, patients with obesity who underwent bariatric surgery with gastric bypass, laparoscopic banding or laparoscopic sleeve gastrectomy had a reduced risk for all-cause mortality at 4.5 years compared with those who underwent nonsurgical obesity management. In 5-year follow-up data from the STAMPEDE trial, which was presented at the American College of Cardiology Scientific Session in 2016, patients with type 2 diabetes and mild to moderate obesity who underwent bariatric surgery had better control of their glycemic index compared with those who were treated by an intensive medical therapy approach.
Further research
More research is needed in this area beyond the mechanism between obesity and CVD, especially in the methods of defining obesity. BMI is not always the most accurate measurement, especially in those who are “skinny fat” or accumulate fat in one area of the body. Understanding the effects of decreasing visceral fat even in the setting of unsubstantial weight loss may help health care professionals guide their patients towards CVD and diabetes prevention. “One of the important things is to understand what are the population-level changes and potential policy changes that will help successfully implement these strategies for the success of primordial prevention on a population level,” Khan said.
More research is also needed for future guidelines that define which patients may benefit from the control of CV risk, CV mortality and overall mortality even in the absence of obesity. Although surgical options may be the best treatment option for certain patients with obesity, it is important to not only identify the risks and benefits that each patient may face, but also identify the surgeons with the experience to perform these procedures and what procedures are best for certain patients. One of the most important areas for future research is determining the best methods for successful weight loss. “Some great work has been done regarding weight loss through behavioral modification in the context of clinical trials,” Ndumele said. “We need better strategies to promote weight loss in real world settings, and not just to promote weight loss, but to maintain weight loss. That’s an area that needs some work.”
Cardiologists as patient advocates
For patients with overweight and obesity, much of the focus is on weight loss. Cardiologists should support the prevention of not only CVD, but obesity itself while implementing practices of intervention. “We’re seeing the problems with obesity, and it is absolutely critical that we as leaders and those who work with patients who have the morbidity and mortality that’s brought on by obesity become involved in efforts to curtail obesity,” Smith said.
Cardiologists should also be aware of patients who are disadvantaged who do not have easy access to healthy foods, which places a pa- tient at risk. “We need to counsel our patients appropriately on how to have health-seeking behaviors that improve access to healthy foods, fresh fruits and vegetables, low-fat dairy products and low saturated protein sources,” Ferdinand said. – by Darlene Dobkowski
This article was originally published in Cardiology Today. It is reprinted with permission. For more content, visit Healio.com/Cardiology

    References:

    1. Biener, Adam, John Cawley, and Chad Meyerhoefer. “The impact of obesity on medical care costs and labor market outcomes in the US.” Clinical Chemistry 64.1 (2018): 108-117.
    2. Ford, Earl S., et al. “Explaining the decrease in US deaths from coronary disease, 1980–2000.” New En- gland Journal of Medicine 356.23 (2007): 2388-2398.
    3. Hales, Craig M., et al. “Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016.” JAMA (2018).
    4. Jensen, Michael D., et al. “2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.” Journal of the American College of Cardiology 63.25 Part B (2014): 2985-3023.
    5. Khan, Sadiya S., et al. “Association of body mass index with lifetime risk of cardiovascular disease and com- pression of morbidity.” JAMA Cardiology (2018).
    6. Look AHEAD Research Group. “Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.” New England Journal of Medicine 369.2 (2013): 145-154.
    7. Michalsky, Marc P., et al. “Cardiovascular risk factors after adolescent bariatric surgery.” Pediatrics (2018): e20172485.
    8. Poirier, Paul, et al. “Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Sci- entific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.” Circulation 113.6 (2006): 898-918.
    9. Reges, Orna, et al. “Association of bariatric surgery using laparoscopic banding, Roux-en-Y gastric bypass, or laparoscopic sleeve gastrectomy vs usual care obesity management with all-cause mortality.” JAMA 319.3 (2018): 279-290.
    10. Schauer, Philip R, et. al. “Surgical treatment and medications potentially eradicate diabetes effectively – STAMPEDE.” Featured Clinical Research II. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.
    11. Sidney, Stephen. “Wrong direction: troubling trends in the rate of U.S. cardiovascular disease deaths.” A report from the National Forum for Heart Disease & Stroke Prevention. Available at: www.nationalforum.org.

    Volume

    July 2018 | Vol. 1 Q3