Challenging the obesity paradox: extreme obesity and COPD mortality in the SUMMIT trial

Abstract

Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the "obesity paradox". Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity. We examined the relationship between body mass index (BMI; defined as underweight: <20 kg·m^-2, normal: 20-25 kg·m^-2, overweight: 25- <30 kg·m^-2, obese class I: 30- <35 kg·m^-2, class II: 35- <40 kg·m^-2 and class III: ≥40 kg·m^-2), morbidity, and mortality in the SUMMIT trial population (n=16 485), characterised by moderate COPD and heightened cardiovascular risk with a substantial proportion with class III obesity. The association between BMI category and time to event was modelled <i>via</i> proportional hazards (reference normal weight) adjusted for demographics and cardiorespiratory disease. Consistent with the paradox, underweight individuals demonstrated higher mortality (hazard ratio (HR) 1.31 (95% CI 1.04-1.64)), with lower mortality among overweight (HR 0.62 (95% CI 0.52-0.73)) and obese class I (HR 0.75 (95% CI 0.62-0.90)). However, mortality increased in obese class III (HR 1.36 (95% CI 1.00-1.86)). Death was primarily attributable to cardiovascular causes. Within a large, multinational cohort with moderate COPD and increased cardiovascular risk, the phenomenon of reduced mortality with obesity did not persist at BMI >40 kg·m^-2, suggesting that obesity may not remain protective at the extremes in this population.