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)

BackgroundObesity 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. ObjectiveTo examine whether a BMI >27 kg/m{superscript 2} is linked to higher risks of all-cause mortality, cardiovascular death, and heart failure (HF) hospitalization in HFrEF patients. MethodsThis 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/m{superscript 2}). ResultsPatients 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. ConclusionAmong 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.