Obesity paradox is consistently demonstrated in cohorts of patients with systolic heart failure (HF). Recent reports suggest that cardiorespiratory fitness modifies the relation between adiposity measurements and mortality. We aimed to investigate the combined effect of obesity and physical capacity, measured by body mass index (BMI) and 6-minute walk distance (SMWD) test, respectively, on the prognosis of patients with systolic HF. We studied 543 consecutive patients with advanced systolic HF at their initial visit to the HF clinic. SMWD was categorized as low (<300 m) or high (≥300 m) physical capacity and BMI according to standard classification. Association of the BMI × SMWD product (kilogram per meter) with total mortality was assessed by Cox proportional hazards analyses. There were 216 deaths during a mean follow-up of 40 months. Obesity paradox was observed in the study cohort but was attenuated in the high physical capacity group. High compared with low physical capacity was associated with significant survival benefit in both the normal-weight and obese patients subgroups (log-rank p=0.003 and p=0.009, respectively). A progressive inverse relation between quartiles of BMI × SMWD product and mortality risk was observed. Compared with the lower quartile (Q1, reference group), Q2 had hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.49 to 0.97), Q3 had HR of 0.64 (95% CI 0.44 to 0.93), and Q4 had HR of 0.40 (95% CI 0.25 to 0.65). In conclusion, obesity paradox exists in patients with systolic HF but is modified by the degree of physical capacity. Therefore, the combined parameter of BMI × SMWD product is more reliable in predicting long-term mortality risk in patients with systolic HF.
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