Among patients with heart failure with preserved ejection fraction (HFpEF), cardiac remodeling, hemodynamics and functional impairment were independently correlated with adiposity while insulin resistance (IR) was not, according to results from the PVDOMICS study published May 5 in JACC.

Including 276 study participants with HFpEF, Yogesh N.V. Reddy, MBBS, MSc, et al., assessed the contribution of diabetes vs. obesity to left heart abnormalities in HFpEF, including measures such as BMI, bioimpedance fat mass, waist circumference and homeostasis-model assessment (HOMA). The authors compared rest and exercise pulmonary capillary wedge pressure (PCWP) responses in patients by obesity, IR status and diabetes diagnosis.

Overall, 89% of participants had an increased waist/height ratio and 60% had a BMI ≥30 kg/m². The proportion of patients with IR and diabetes among those with a BMI ≥30 kg/m² vs. <30 kg/m² was 69% and 45% vs. 40% and 25% respectively (p<0.0001 for both vs. obesity phenotype).

Participants with obesity were more likely to have greater biventricular enlargement, worse exercise performance, poorer quality of life, and higher rest and exercise PCWP (p<0.01 for all), and all measures of adiposity evaluated, including greater fat mass, BMI and waist circumference, were associated with higher rest and exercise PCWP (p<0.01 for all).

Meanwhile, no association was noted for presence of IR with worse left heart remodeling or HOMA-IR with higher rest and exercise PCWP (+0.01 mm Hg; p=0.84). Investigators saw similar results when replacing IR with diabetes diagnosis.

These results were replicated in an independent cohort of 254 patients with HFpEF. According to the authors, their findings suggest that "excess adiposity (as estimated by BMI or more specifically by waist-based indices or fat mass estimation) plays a central role in contributing to abnormal left heart reserve in patients with HFpEF, with associated impairments in exercise tolerance and [quality of life], whereas diabetes and associated IR may be more of an epiphenomenon associated with adiposity."

In an accompanying editorial comment, Jennifer E. Ho, MD, FACC, Zsu-Zsu Chen, MD, MPH, and Emily S. Lau, MD, MPH, FACC, add that "clinical efforts should focus on weight loss strategies including incretin-based therapies. However, we cannot ignore the implications of metabolic dysfunction and [type 2 diabetes] that so often compound obesity, and their enormous downstream consequences, not only for HFpEF, but also for overall health."