Cardiometabolic Chronicle

The Spectrum of Cardiovascular Prevention: Obesity Paradox, Physical Activity, Sedentary Behaviors and Emerging Therapeutics in Type 2 Diabetes Mellitus

Now with that being said, I want to make sure that we don’t pass the wrong message that obesity is a good thing, because if these individuals didn’t become obese in the first place, it could have likely prevented the development of cardiovascular disease. So, we still need to make all the effort we can to prevent obesity.7 But I think that one important point that has come out of these studies and a paradigm change in how we think about patients compared to 15-20 years ago, is that we should pay greater attention to heart failure patients with a normal BMI and clearly in those underweight, perhaps more than heart failure patients with class I obesity, since the former have a higher all-cause and cardiovascular mortality risk.

I believe that the obesity paradox is a real phenomenon, but we still don’t clearly understand the underlying mechanisms responsible for it, nor do we have data from large multicenter randomized controlled trials looking at targeting obesity in the setting of heart failure or other established cardiovascular disease, so we can’t say this with certainty. One hypothesis we have proposed as a group is that patients with obesity in addition to having excess body fat, typically also have excess lean mass, which is a surrogate for skeletal muscle mass.8 And we know that high lean mass is associated with improved prognosis in some cardiovascular conditions, including heart failure. So, it is plausible to think that patients with obesity may do better because they have that excess lean mass. We recently published a review article in Current Problems in Cardiology discussing the role of lean mass and different body composition phenotypes (sarcopenia, sarcopenic obesity and cachexia) in determining cardiorespiratory fitness and overall prognosis in heart failure, where we make a strong distinction between the use of BMI and body composition compartments such as lean mass.9 For example, heart failure patients with excess body fat (i.e., obesity) but a low amount of lean mass (also called sarcopenic obesity) are the ones who actually do worse and have the most impaired cardiorespiratory fitness, even if they have class I obesity, so it is important to make that distinction.

  1. 1. Ortega, Francisco B., Carl J. Lavie, and Steven N. Blair. “Obesity and cardiovascular disease.” Circulation Research 118.11 (2016): 1752-1770.
  2. 2. Carbone, Salvatore, et al. “Obesity paradox in cardiovascular disease: where do we stand?.” Vascular Health and Risk Management 15 (2019): 89 - 100.
  3. 3. Carbone, Salvatore, Carl J. Lavie, and Ross Arena. “Obesity and heart failure: focus on the obesity paradox.” Mayo Clinic Proceedings 92.2 (2017): 266 – 279.
  4. 4. Horwich, Tamara B., et al. “The relationship between obesity and mortality in patients with heart failure.” Journal of the American College of Cardiology 38.3 (2001): 789-795.
  5. 5. Padwal, R., et al. “The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.” International Journal of Obesity 38.8 (2014): 1110 - 1114.
  6. 6. Romero-Corral, Abel, et al. “Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.” The Lancet 368.9536 CLINICAL CONVERSATIONS 26 (2006): 666-678.
  7. 7. Lavie, Carl J., et al. “Healthy weight and obesity prevention: JACC Health Promotion Series.” Journal of the American College of Cardiology 72.13 (2018): 1506 - 1531.
  8. 8. Carbone, Salvatore, et al. “Obesity, body composition and cardiorespiratory fitness in heart failure with preserved ejection fraction.” Future Cardiology 13.5 (2017): 451-463.
  9. 9. Carbone, Salvatore, et al. “Lean mass abnormalities in heart failure: the role of sarcopenia, sarcopenic obesity and cachexia.” Current Problems in Cardiology (2019).
  10. 10. Ortega, Francisco B., et al. “Body mass index, the most widely used but also widely criticized index: would a criterion standard measure of total body fat be a better predictor of cardiovascular disease mortality?.” Mayo Clinic Proceedings. 91.4 (2016): 443 - 455.
  11. 11. Piercy, Katrina L., and Richard P. Troiano. “Physical activity guidelines for Americans from the US Department of Health and Human Services: cardiovascular benefits and recommendations.” Circulation: Cardiovascular Quality and Outcomes 11.11 (2018): e005263, also available at https:// Physical_Activity_Guidelines_2nd_edition.pdf
  12. 12. Fletcher, Gerald F., et al. “Promoting physical activity and exercise: JACC health promotion series.” Journal of the American College of Cardiology 72.14 (2018): 1622-1639.
  13. 13. Stamatakis, Emmanuel, et al. “Sitting time, physical activity, and risk of mortality in adults.” Journal of the American College of Cardiology 73.16 (2019): 2062-2072.
  14. 14. Lavie, Carl J., et al. “Sedentary behavior, exercise, and cardiovascular health.” Circulation Research 124.5 (2019): 799-815.
  15. 15. Lee, I-Min, et al. “Association of Step Volume and Intensity With All-Cause Mortality in Older Women.” JAMA Internal Medicine (2019).
  16. 16. Arnett, Donna K., et al. “2019 ACC/AHA guideline on the primary prevention of cardiovascular disease.” Journal of the American College of Cardiology (2019): 26029.
  17. 17. UK Prospective Diabetes Study (UKPDS) Group. “Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).” The Lancet 352.9131 (1998): 837-853.
  18. 18. Zinman, Bernard, et al. “Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.” New England Journal of Medicine 373.22 (2015): 2117-2128.
  19. 19. Neal, Bruce, et al. “Canagliflozin and cardiovascular and renal events in type 2 diabetes.” New England Journal of Medicine 377.7 (2017): 644-657.
  20. 20. Wiviott, Stephen D., et al. “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” New England Journal of Medicine 380.4 (2019): 347- 357.
  21. 21. Perkovic, Vlado, et al. “Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.” New England Journal of Medicine 380.24 (2019): 2295-2306.
  22. 22. Marso, Steven P., et al. “Liraglutide and cardiovascular outcomes in type 2 diabetes.” New England Journal of Medicine 375.4 (2016): 311-322.
  23. 23. Marso, Steven P., et al. “Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.” New England Journal of Medicine 375.19 (2016): 1834-1844.
  24. 24. Hernandez, Adrian F., et al. “Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.” The Lancet 392.10157 (2018): 1519-1529.
  25. 25. American Diabetes Association. “9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2019.” Diabetes Care 42.Supplement 1 (2019): S90-S102.
  26. 26. Carbone, Salvatore, et al. “Glucose-lowering therapies for cardiovascular risk reduction in type 2 diabetes mellitus: State-of-the-Art Review.” Mayo Clinic Proceedings 93.18 (2018): 1629 – 1647.


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