This is supported by the U-shaped association of BMI and mortality in patients with HF, with increased mortality being observed in patients with a BMI <18.5 . In addition to direct effects of cachexia on mortal- ity, this reverse epidemiology may be explained partly by decreased levels of lipoprotein molecules and adipocytes in the setting of cachexia distorting their endotoxin-scav- enging role, predisposing patients with HF with cachexia to inflammatory consequences of endotoxemia.221 It is also interesting to note that brain natriuretic pep- tide levels are significantly lower in overweight and obese patients with HF compared with lean patients.222 224 A potential important explanation includes the increase in the clearance of active natriuretic peptides by means of an increased expression of clearance receptors on adi- Furthermore, obese subjects are frequently treated for hypertension and coronary artery disease. Pharmacological treatment reduces plasma levels of cardiac natriuretic peptides, and this effect may explain, in part, the lower brain natriuretic peptide levels of some asymptomatic subjects with increased BMI values. Di- minished activation of natriuretic peptides, enhanced protection against endotoxin or inflammatory cytokines, and increased nutritional and metabolic reserve may ex- plain some aspects of reverse epidemiology with obesity and mortality in patients with HF. Still, it is important to Bozkurt et al note that although obese patients have lower levels of brain natriuretic peptide than nonobese patients, brain natriuretic peptide levels predict worse symptoms, im- paired hemodynamics, and higher mortality in any BMI category, even in obese patients.222 It has also been proposed that obese patients may simply have less ad- vanced illness, earlier diagnosis, or competing diagno- ses with excess symptoms such as fatigue and dyspnea caused part by their excess body weight. 