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Clinical Implications of the Obesity Paradox in Patients with Coronary Artery Disease

Published:October 05, 2009DOI:https://doi.org/10.1016/j.amjmed.2009.06.012
      Obesity is a well established and independent risk factor for cardiovascular disease and mortality in the general population. This risk appears to be mediated, at least in part, through obesity-related comorbidities such as diabetes mellitus, hypertension, and dyslipidemia.
      • Must A.
      • Spadano J.
      • Coakley E.H.
      • et al.
      The disease burden associated with overweight and obesity.
      Virtually all national and international guidelines recommend weight loss for overweight and obese patients for the primary prevention of cardiovascular disease, and these recommendations also have been extended to overweight and obese patients with cardiovascular disease.
      Despite the association between obesity and cardiovascular risk in the general population, a multitude of studies have described an inverse correlation between body mass index (BMI) and mortality in patients with cardiovascular disease, including those with stable coronary artery disease. A meta-analysis combining data from 40 cohort studies and including more than 250,152 patients with coronary artery disease and BMI ranging from low to severely obese confirmed this inverse relationship.
      • Romero-Corral A.
      • Montori V.M.
      • Somers V.K.
      • et al.
      Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.
      The association between elevated BMI and improved survival has been termed the “obesity paradox.”
      In this issue of The American Journal of Medicine, Lavie et al further investigate the obesity paradox in a cohort of 529 patients with coronary artery disease enrolled in a cardiac rehabilitation and exercise training program.
      • Lavie C.J.
      • Milani R.V.
      • Artham S.M.
      • et al.
      The obesity paradox, weight loss, and coronary disease.
      In assessing the impact of obesity on mortality in patients with coronary artery disease, the research group used both BMI, a traditional index of obesity, as well as a more direct measure of adiposity, percent body fat. Approximately three quarters of subjects in the study were overweight or obese, and over one half of patients had high percent body fat, defined as percent body fat >25% in men and >35% in women. Consistent with prior studies, survival analysis showed that the risk of death decreased with increasing BMI. Total mortality was considerably lower in the baseline overweight/obese coronary artery disease patients than in patients with baseline BMI <25 kg/m2. Patients with baseline BMI ≥35 kg/m2 had the lowest mortality risk (1.8%). Some investigators have suggested that the finding that higher BMI is associated with lower mortality risk is de facto evidence that BMI is an invalid measure of adiposity.
      • Romero-Corral A.
      • Montori V.M.
      • Somers V.K.
      • et al.
      Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.
      However, Lavie et al demonstrate that coronary artery disease patients with direct measures of high baseline percent body fat also were at substantially lower mortality risk (3.8%) compared with those with more normal percent body fat (10.6%).
      • Lavie C.J.
      • Milani R.V.
      • Artham S.M.
      • et al.
      The obesity paradox, weight loss, and coronary disease.
      While a number of potential hypotheses may explain the paradoxical association between obesity and improved outcomes in patients with established cardiovascular disease, the fundamental clinical question is whether weight loss should be recommended as a therapeutic goal in overweight and obese patients with coronary artery disease. Lavie et al compare mortality rates in patients participating in the cardiac rehabilitation program who lost various degrees of weight. However, because all patients who were overweight or obese were advised to lose weight, rather than being a comparison of a therapeutic strategy of more or less purposeful weight loss, this is really a comparison of responders/more adherent patients with nonresponders/less adherent patients. This introduces a substantial bias to this component of the study and prevents any meaningful conclusions about either the safety or efficacy of purposeful weight loss in this cohort.
      It is time to revisit thinking about obesity in the context of chronic illnesses, including coronary artery disease. The prognostic implications and hence the pathophysiologic consequences of obesity in patients with cardiovascular disease appear to be different from obesity in the general population without illness. The knowledge gained and recommendations derived from one cohort should not be transferred by conjecture to other groups. In order to determine whether weight loss is an efficacious and safe therapeutic intervention in coronary artery disease patients, prospective randomized clinical outcome trials are necessary and critical.

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