March 3, 2026

Peak oxygen consumption as a modifier of the obesity paradox in patients with obesity with heart failure with reduced ejection fraction

Key Result

Obesity in patients with HFrEF lowered all-cause mortality versus normal weight (HR 0.46), but elevated peak VO2 was associated with a U-shaped mortality curve (P for interaction=0.001).

Key Points

Patients with obesity in heart failure had better survival outcomes than those with normal weight, highlighting the obesity paradox.
For 819 patients analyzed, obesity improved mortality, with a hazard ratio of 0.46 and a significant difference in peak oxygen consumption levels.
Observational analysis of exercise capacity via cardiopulmonary testing revealed a U-shaped relationship between peak oxygen consumption and mortality for those with obesity in heart failure, unlike others' linear trend . Peak oxygen consumption's relation to mortality indicates that higher levels may eventually diminish the survival benefit seen in obesity, necessitating further study.

Structured PICO

Does peak VO2 modify the survival advantage of obesity in patients with HFrEF?

Population

819 patients with HFrEF (LVEF <40%) and BMI >18.5 kg/m2 who underwent maximal cardiopulmonary exercise testing. Median age 59, 75.2% male.

Intervention

Obesity (BMI ≥25.0 kg/m2) and peak VO2 assessment

Comparator

Normal weight (BMI 18.5–22.9 kg/m2) and overweight (23.0–24.9 kg/m2)

Outcome

All-cause mortalityhard clinical

In patients with HFrEF, obesity is associated with a survival benefit, but this advantage may diminish at higher levels of exercise capacity, demonstrating a U-shaped relationship between peak VO2 and mortality.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background: Obesity is linked to adverse health effects, but paradoxically improves survival in heart failure (HF). Peak oxygen consumption (VO 2 ), a measure of exercise capacity, is a key prognostic indicator in HF. We examined the interaction between obesity and peak VO 2 in predicting survival in patients with HF with reduced ejection fraction (HFrEF). Methods: We retrospectively reviewed 18,879 patients who underwent maximal cardiopulmonary exercise testing using the modified Bruce ramp protocol between 2012 and 2020. The inclusion criteria were left ventricular ejection fraction 18.5 kg/m 2 . Patients were classified as those with normal weight (BMI: 18.5–22.9 kg/m 2 ), overweight (23.0–24.9 kg/m 2 ), or obesity (≥25.0 kg/m 2 ) per 2020 Korean Society for the Study of Obesity guidelines. Results: For the 819 included patients (292 with normal weight, 197 with overweight, 330 with obesity), median age was 59 (interquartile range IQR: 49–67) years, 75.2% were male, and the median BMI was 24.1 (IQR: 22.1–26.5) kg/m 2 . Patients with obesity achieved the highest workload, peak VO 2 , and exercise time (all P < 0.001). They also had lower all-cause mortality versus patients with normal weight (hazard ratio 0.46, 95% confidence interval 0.25–0.82, P = 0.009). In patients with obesity, elevated peak VO 2 was associated with a U-shaped mortality curve, unlike the linear relationship in other groups ( P for interaction = 0.001). Conclusions: Patients with obesity and HFrEF showed better survival, consistent with the obesity paradox. However, the U-shaped relationship between peak VO 2 and mortality in this group suggests the survival advantage may diminish at higher levels of exercise capacity, warranting further investigation.