The Obesity Paradox in Heart Failure: Is It Still Valid in Light of New Therapies?

Abstract

<b><i>Background:</i></b> Obesity increases the risk of cardiovascular disease and heart failure (HF). However, in patients with established HF, many studies observed greater survival with increasing adiposity. This counterintuitive observation has been termed the “obesity paradox.” In recent years, new HF therapies have emerged that improve prognosis in patients with HF. Some of these, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i), cause weight loss and may therefore interfere with the obesity paradox. <b><i>Summary:</i></b> This article is a narrative review on the relationship between body weight and outcomes in patients with HF with special focus on new HF treatments. PubMed was searched for studies reporting the prognostic impact of obesity in HF from 2002 to February 22, 2022. More than 400 records were examined, with 150 being included in the present review. Literature provides evidence for an obesity paradox in a broad range of HF patients, including acute and chronic HF across the spectrum of left ventricular ejection fraction. It has been verified in HF patients treated with SGLT2i but not in those using sacubitril/valsartan. Cardiorespiratory fitness and the severity of HF seem to be important confounders of the obesity paradox in HF. While unintentional weight loss is associated with a poor prognosis in HF, weight loss associated with SGLT2i treatment appears safe. <b><i>Key Messages:</i></b> Consensus has yet to emerge as to whether the obesity paradox is a true phenomenon in HF. As cardiorespiratory fitness is strongly associated with prognosis and significantly modifies the relationship between adiposity and survival in HF, regular physical activity is recommended irrespective of the body weight. In HF patients with severe obesity, a modest weight reduction of 5–10% may be reasonable to improve HF symptoms and quality of life.