Association of body mass index with mortality in COPD through exacerbations and cardiovascular events

INTRODUCTION: The mechanisms through which body mass index (BMI) influences the prognosis of chronic obstructive pulmonary disease (COPD) remain poorly understood. This study investigates whether BMI influences all-cause mortality in patients with COPD through mediating effects of exacerbations and cardiovascular events. METHODS: Data were obtained from a multicentre prospective COPD cohort (NCT02800499). BMI was assessed both continuously and categorically as 27 kg/m² (high). The primary outcome was all-cause mortality and secondary outcomes were moderate-to-severe exacerbations and cardiovascular events. Mediation analyses were applied to quantify the contribution of these events to the association between BMI and all-cause mortality. RESULTS: Among 3314 patients with COPD, those with low BMI had a higher risk of mortality (adjusted OR, 1.46; 95% CI 1.04 to 2.07), whereas no significant difference was observed among those with high BMI. Mediation analyses indicated that exacerbations partially mediated the relationship between BMI and all-cause mortality, explaining 11.9% of the increased mortality among patients with low BMI and 21.9% of the reduced mortality among those with high BMI. Meanwhile, cardiovascular events showed mediating effects in the opposite direction, contributing to 5.2% lower mortality among patients with low BMI and 11.5% higher mortality among those with high BMI. CONCLUSIONS: BMI was non-linearly associated with all-cause mortality in COPD. Exacerbations mediated the excess mortality risk among patients with low BMI, whereas the decreasing risk of cardiovascular events in this group contributed to a countervailing effect that tempered the overall association between low BMI and mortality.