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 prevalent in patients with heart failure with reduced ejection fraction (HFrEF). With the advent of glucagon-like peptide 1 analogues, understanding the relationship between body mass index (BMI) and clinical outcomes in HFrEF is crucial.

OBJECTIVE: This study investigated whether a BMI > 27 kg/m2 is associated with higher rates of all-cause mortality, cardiovascular mortality, and heart failure (HF) hospitalization in patients with HFrEF.

METHODS: A total of 1017 clinically stable and medically optimized HFrEF patients from the NorthStar study (enrolled 2005-2009) were analyzed. Patients were followed until 2023 using Danish nationwide registries. The primary outcome was all-cause mortality, while secondary outcomes included cardiovascular mortality, HF hospitalization, and a composite of all-cause mortality or HF hospitalization. Cox proportional-hazards models adjusted for prognostic factors were used to assess associations. Interaction analyses for the primary outcome were conducted for BMI categories (< 24, 24-27, > 27 kg/m2) and prognostic variables.

RESULTS: Compared to patients with a BMI of 24-27 kg/m2, those with a BMI > 27 had a higher prevalence of diabetes (27.8% vs. 17.7%), similar HF etiology (ischemic: 57.5% vs. 58.7%), and lower NT-proBNP levels (median 776 vs. 1163 pg/mL). Over a median follow-up of 8.8 years, the primary outcome occurred in 235 patients (71.9%) with BMI 24-27, and 338 patients (71.8%) with BMI > 27 (ref. BMI 24-27: Hazard ratios (HR) 1.11 [0.94 - 1.32]). 124 patients (37.9%) and 186 patients (39.5%) died from cardiovascular causes, respectively (HR 1.21 [0.96 - 1.53]). A first worsening HF event occurred in 214 patients (65.4%) and 317 patients (67.3%) (HR 1.12 [0.93 - 1.33]). A combined outcome of all-cause death and first worsening HF events occurred in 277 patients (84.7%) and 398 patients (84.5%) (HR 1.09 [0.93 - 1.27]). The subgroup analyses revealed a significantly higher mortality rate for BMI > 27 vs 24-27 in patients with ischemic cardiomyopathy (HR 1.31 [1.05-1.64]), but not in patients with non-ischemic cardiomyopathy (HR 0.86 [0.66-1.12]).

CONCLUSION: In HFrEF patients, a BMI > 27 was not associated with increased mortality, contradicting the "obesity-survival paradox." In fact, patients with ischemic cardiomyopathy and a BMI > 27 may be associated with a higher mortality rate.