New Insights into the "Obesity Paradox" and Cardiovascular Outcomes

Abstract

Overweight and obesity are increasing in epidemic proportions both in the United States (US) and throughout the Western World [1]. A considerable burden from cardiovascular disease (CVD) in the US has been “heavily” impacted by the obesity epidemic, with the current estimation of obesity prevalence in US children and adolescents being just under 20%, with a prevalence >33% in adults 24-74 years of age [2]. Alarmingly, the proportion of patients with either severe or morbid obesity is increasing even more so than are overweight and obesity per se [1]. Almost all of the major CVD risk factors, including glucose abnormalities (impaired fasting glucose, metabolic syndrome, and type 2 diabetes mellitus), lipid disorders (especially elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol), hypertension (HTN) and left ventricular hypertrophy, and physical inactivity ,as well as sleep apnea, are all adversely impacted by overweight and obesity [1,3-5]. In addition, overweight and obesity may be independent risk factors for coronary heart disease (CHD) and have adverse impacts on almost all CVD, including HTN, heart failure (HF), atrial fibrillation (AF), and sudden cardiac death [1,3-5].Despite the powerful impact, however, that overweight and obesity have on CHD risk factors, CHD, and other CVD, numerous studies and meta-analyses have addressed the “obesity paradox,” which indicates that once CVD becomes established, including CHD, HF, HTN, and AF, overweight and obese have a better prognosis than do their lean counterparts with the same CVD [1,3-7]. The obesity paradox has been discounted by some experts who have suggested that this may be due to such factors as sample size errors or by unmeasured confounding factors, as was also suggested in a recent major study of in-hospital mortality in acute myocardial infarction [3,8,9]. However, even very large meta-analyses have demonstrated this paradox in CHD and HF [6,7]. In fact, Romero-Corral and colleagues [6] evaluated 40 studies of more than 250,000 patients with CHD and demonstrated that in patients grouped according to body mass index (BMI), those in the lowest or “normal” BMI group had the highest all-cause mortality, whereas better survival was observed in higher BMI groups. The overweight had the lowest relative risk, whereas obesity and severe obesity have no increased mortality risk. Likewise, in HF, Oreopoulos and colleagues [7] reviewed 29,000 patients from 9 major HF studies and demonstrated reductions in CV and total mortality of 19% and 16%, respectively in the overweight and 40% and 33%, respectively in the obese compared with normal-weight patients with HF. Many have blamed the obesity paradox on relatively poor accuracy of BMI to reflect true body fatness, and we agree that other measures of body composition [including waist circumference (WC), waist-to-hip ratio, and measures of visceral and peripheral adiposity] may all be superior to BMI in the assessment of body fatness [1,3-6,10-15]. We have demonstrated the obesity paradox, however, in both HF [14,16] and CHD [13,15,17-19] with both BMI and percent body fat (BF), demonstrating that BF was an independent predictor of better event-free survival. In CHD, we have demonstrated that low BF (≤ 25% in men and ≤ 35% in women) predicted a nearly three-fold increase in mortality compared with high BF [10,12,14]; also, we demonstrated that the combination of low BF and low BMI (< 25 kg/m