Associations of Body Mass Index on worsening of heart failure and mortality in patients with heart failure and reduced left ventricular ejection fraction: A 10-year follow-up study (A NorthStar Substudy)

Background Obesity is common in heart failure with reduced ejection fraction (HFrEF). As anti-obesity treatments advance, understanding how body mass index (BMI) affects outcomes in HFrEF is increasingly important. Objective To examine whether a BMI >27 kg/m² is linked to higher risks of all-cause mortality, cardiovascular death, and heart failure (HF) hospitalization in HFrEF patients. Methods This study included 1,017 clinically stable, medically optimized HFrEF patients from the NorthStar study (2005–2009), followed through 2023 using Danish registries. Outcomes were assessed with Cox models adjusted for prognostic factors. The primary endpoint was all-cause mortality; secondary endpoints included cardiovascular death, HF hospitalization, and a composite of mortality or hospitalization. Subgroup analyses compared BMI categories (<24, 24–27, >27 kg/m²). Results Patients with BMI >27 had more diabetes (27.8% vs. 17.7%) and lower NT-proBNP (median 776 vs. 1,163 pg/mL) than those with BMI 24–27, with similar HF etiology. Over a median 8.8 years, 821 patients (80.7%) died, including 444 cardiovascular deaths, and 740 (72.8%) were hospitalized for HF. A BMI of 35 vs. 27 was associated with non-significant increased all-cause mortality (HR 1.18, 95% CI 0.94–1.48) but significantly higher cardiovascular mortality (HR 1.42, 95% CI 1.05–1.92), HF hospitalization (HR 1.33, 95% CI 1.05–1.67), and composite outcome (HR 1.30, 95% CI 1.06–1.60). Subgroup analysis showed higher mortality with BMI >27 vs. 24–27 in ischemic cardiomyopathy (HR 1.31, 95% CI 1.05–1.64), but not in non-ischemic (HR 0.86, 95% CI 0.66–1.12), interaction p=0.015. Conclusion Among HFrEF patients—especially those with ischemic cardiomyopathy—BMI >27 is associated with worse outcomes, challenging the “obesity-survival paradox” and highlighting the importance of effective weight management.