Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial

An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity—the waist-to-height ratio (WHtR)—focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

The PARAGON-HF trial randomized 4796 patients with heart failure (HF) and ejection fraction ≥45% to valsartan or sacubitril/valsartan. The current work characterizes the association of BMI and WHtR with clinical features, outcomes, and the response to neprilysin inhibition.

About half (49%) of the participants were considered obese by BMI (≥30 kg/m²), but nearly every patient (96%) had central adiposity (WHtR ≥.5). Among patients who were not obese (BMI <30 kg/m²), 860 (37%) had marked central adiposity (WHtR ≥.6). Higher BMI and WHtR were both associated with higher risk of total HF hospitalizations, but as compared with BMI, WHtR was linearly associated with HF outcomes and identified a higher proportion of patients who had a particularly elevated risk (i.e. 30% or greater). An obesity-survival paradox (i.e. improved outcomes in those with greater adiposity) was apparent with BMI in unadjusted analyses, but it was not observed with WHtR. Although neprilysin inhibition appeared to have greater effects on HF outcomes in patients with higher BMI and WHtR, analyses of interaction with obesity metrics did not show significant heterogeneity across the range of values for adiposity.

In PARAGON-HF, in contrast with BMI, nearly every patient with HFpEF had central adiposity (as assessed by WHtR), and the risks of adverse HF events were more robustly related to WHtR. These data challenge the current reliance on BMI as an appropriate metric of adiposity, and they suggest that—rather than obesity-related HFpEF being regarded as a select HFpEF subgroup—central adiposity is a ubiquitous feature of HFpEF.

https://www.clinicaltrials.gov. Unique identifier: NCT01920711