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

Abstract

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.

The Role of CCTA-derived Cardiac Structure and Function Analysis in the Prediction of Readmission in Nonischemic Heart Failure

“…Obesity is prevalent among HF patients, but whether it can serve as an independent prognostic factor for HF outcomes remains a topic of debate [21]. Some relevant studies have suggested that overweight and mildly to moderately obese HF patients may have longer survival rates than normal-weight or underweight HF patients [22,23]. The potential explanation for this difference may be related to whether fat leads to excessive accumulation of WAT and myocardial fat infiltration [24,25].…”

“…We hypothesized that, compared to BMI, EAT might be a more precise indicator of obesity, and thus, measuring EAT could better assess disease progression. In fact, previous research has confirmed that EAT participates in the occurrence and progression of cardiovascular diseases by synthesizing and secreting proinflammatory mediators and neurohormones such as IL-1β, IL-6, TNF-α, MCP-1, resistin, visfatin, and others [23]. Currently, research on EAT in HF patients is primarily focused on those classified based on ejection fraction (EF) [26].…”

Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF

“…Several studies performed in the last two decades consistently showed that mild to moderate obesity-even if associated with increased risk for cardiovascular diseases and all-cause mortality in healthy subjects-prevents early death in chronic HF. This phenomenon has also been shown for a plenty of other cardiovascular disease conditions and is termed the 'obesity paradigm' (35,36). It has been clearly shown that muscle wasting/sarcopenia, which affects 20%-50% of patients with chronic HF including patients in young age groups, even before a reduction in total body weight sets in, relates with impaired exercise tolerance, quality of life and mortality (33,(37)(38)(39).…”

“…Even though obesity is highly prevalent in HFpEF and seems to be of causative impact at least in a subset of HFpEF patients with a distinct obesity phenotype, the so called obesity paradigm indicating higher mortality in patients with lower BMI has been shown consistently in different HFpEF populations ( 36 , 40 – 42 ). Recently, this was confirmed in a secondary analysis of the DELIVER trial analyzing safety and efficacy of the SGLT2 inhibitor dapagliflozin vs. placebo in 6,263 patients with HFpEF according to baseline BMI.…”

How Should Weight Control and Caloric Intervention Be Implemented for Obese Heart Failure Patients?

“…Consistent results were seen in small Japanese populations, although the cutoff for the definition of obesity (BMI >25 kg/m 2 ) varied. This phenomenon, widely known as the “obesity paradox,” implies that a higher BMI is associated with a better prognosis for patients with HF [4].…”