In the Uppsala study, insulin sensitivity, but not anthropo- metric indexes of obesity, was independently predictive of In a cohort study from Greece, individuals with normal BMI and metabolic syndrome were at substantially higher risk of HF at 6 years compared with obese individu- als without metabolic syndrome.198 Analyses from MESA (Multi-Ethnic Study of Atherosclerosis) suggest that inflam- mation may potentiate the link between obesity and the risk of developing HF. Although the risk of HF was 83% higher in obese compared with nonobese subjects after adjustment for traditional risk factors, the relationship be- tween obesity and incident HF was no longer significant after adjustment for the inflammatory biomarkers.199,200 Obesity and Outcomes in Patients With Established HF: The Obesity Paradox Overweight and obesity are exceedingly prevalent in HF, although the prevalence may vary depending on the pop- ulation studied. However, recent studies have shown that 29% to 40% of patients with HF are overweight and 30% to 49% are obese, with a significantly higher prevalence Figure 5. Cumulative incidence curves for all-cause death according to category of body mass index (BMI) at the baseline examination. Vertical bars indicate standard errors of the incidence estimates at 3 years of follow-up. Data shown are truncated at 3.5 years. Reprinted from Kenchaiah et al.201 Copyright 2007, American Heart Association, Inc. Management of Comorbidities in Chronic Heart Failure CLINICAL STATEMENTS AND GUIDELINES of obesity in patients with HFpEF compared with patients Although obesity is well established as a risk factor for CVD and incident HF, as described above, obesity, as measured by BMI or other anthropometric indexes, is not a risk factor for adverse outcomes in patients with established HF. This reversal of traditional epidemiology, or the obesity paradox, has now been well documented in numerous studies in the HF medical literature. 