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.

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.

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 (27 kg/m²).

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.

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement No external funding was received. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the Danish Ethics Committee (KF 01/2724936) and the extended follow-up was approved by the Danish Data Protection Agency (Approval number P-2019-348). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data obtained through the nationwide registers in Denmark can be made available only through research on Danish servers hosted in highly protected research environments where researchers can be granted access and permission with encrypted person identification. Access to raw data can be gained only through collaboration with the authors or other Danish institutions that already have been granted access. Please contact the first author with any questions regarding data access.