The obesity paradox in heart failure: is it still valid in light of new therapies?

Background: 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.Summary: 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 22nd 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 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. Key messages: 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 from 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.

Automated summary

This article discusses the obesity paradox in patients with heart failure (HF) and the potential interference of new HF treatments, such as SGLT2 inhibitors. The literature provides evidence for the obesity paradox in various HF patients, and it has been observed in SGLT2 inhibitor-treated patients but not in those using sacubitril/valsartan. Cardiorespiratory fitness and HF severity appear to be important factors influencing the obesity paradox in HF. Unintentional weight loss is associated with a poor prognosis, but weight loss associated with SGLT2 inhibitor treatment appears to be safe.