A new pooled analysis suggests that measures of abdominal adiposity, such as waist-to-height ratio, are better predictors of clinical outcomes than body mass index (BMI) alone in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Obesity is highly prevalent in this patient population and is linked to an increased risk of mortality and disability.

This participant-level pooled analysis included data from five international randomised clinical trials: DELIVER (NCT03619213), PARAGON-HF (NCT01920711), TOPCAT (NCT00094302), I-Preserve (NCT00095238), and CHARM-Preserved (NCT00634712). The study evaluated the association between adiposity-related anthropometrics—specifically BMI, waist circumference (WC), and waist-to-height ratio (WHtR)—and clinical outcomes.

The cohort consisted of 21,479 adults with HFmrEF/HFpEF. The primary endpoints were heart failure (HF) events and mortality, assessed both overall and stratified by age and sex.

At baseline, 46% of participants had a BMI of ≥30 kg/m², meeting the criteria for obesity. However, 95% had an elevated WC or WHtR, indicating a high prevalence of abdominal adiposity. Notably, among participants with a BMI <30 kg/m², 89% still exhibited excess abdominal adiposity, a finding that was more common in older and female participants.

The analysis revealed that while BMI had complex J- and U-shaped associations with clinical outcomes, a higher WHtR was linearly associated with an increased risk of both HF events and mortality. This association was particularly strong in younger participants for both BMI and WHtR in relation to cardiovascular death or HF hospitalisation (Pinteraction <0.001 for both).

Crucially, a higher WHtR was independently associated with adverse outcomes, regardless of the patient's BMI. Conversely, a higher BMI was independently associated with HF hospitalisation, irrespective of WHtR. Patients with elevations in both BMI and WHtR experienced the highest rates of cardiovascular death or HF hospitalisation compared to those with only one elevated measure.

The findings challenge the utility of BMI as the sole metric for defining obesity and assessing risk in patients with HFmrEF/HFpEF. The study authors concluded that, “WC or WHtR assessment identifies a substantial number of individuals with abdominal obesity despite BMI <30 kg/m², and may enhance risk stratification beyond BMI alone in HFmrEF/HFpEF.” These simpler measures could provide a more accurate picture of risk by identifying central adiposity, which may be missed by BMI alone, especially in older adults and women.

This study was funded by various sources for the individual trials, including AstraZeneca, Novartis, the National Heart, Lung, and Blood Institute (NHLBI), Bristol-Myers Squibb, and Sanofi-Aventis.

References

1. Ostrominski JW, Højbjerg Lassen MC, Butt JH, et al. Adiposity-Related Anthropometrics and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Clinical Trials. J Am Coll Cardiol. 2025;86(20):1760-1777. https://doi.org/10.1016/j.jacc.2025.08.012

2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726. https://doi.org/10.1093/eurheartj/ehab368

Disclaimer: The information presented in this article is for educational purposes only. Any quotes included reflect the opinions of the individual quoted, and do not necessarily reflect the views of the publisher. The publisher does not guarantee the accuracy or completeness of the content and accepts no responsibility for any errors, or any consequences arising from its use.