Varying Effects of Body Mass Index and Mortality in Different Risk Groups

It is unclear why high body mass index (BMI) is associated with a lower risk of death in patients with cardiovascular disease (CVD). We hypothesized that the impact of higher BMI varies by the patient's baseline risk of death. We analyzed data from 14 prospective studies conducted by us in 50 countries of 170,470 patients: 22.8% without CVD, 29.4% with stable CVD and 47.8% with acute coronary syndromes (ACS). Compared with overweight (BMI 25 to 29.9 kg/m²), normal weight (BMI 20 to 24.9 kg/m²), and underweight (BMI < 20 kg/m²) were associated with higher mortality in all cohorts. Compared with overweight, the risk of death among those with obesity (BMI ≥ 30 kg/m²) varied depending on the population studied: HR (95% confidence interval) in those without CVD, with stable CVD, and with ACS were 1.20 (1.01 to 1.45; p = 0.04), 1.08 (1.02 to 1.15; p = 0.01), and 1.01 (0.93 to 1.10; p = 0.72), respectively. The BMI associated with lowest mortality increased as cohort risk increased (no-CVD 27.2 kg/m², stable CVD 28.1 kg/m², and ACS 30.9 kg/m²; p <0.001). Within each cohort, the optimal BMI value was higher in the high-risk subgroup. In the ACS cohort, low-risk patients had an optimal BMI value of 29.1 kg/m² while in the high-risk group higher BMI was associated with lower risk of death (interaction-p <0.001). In conclusion, between and within cohorts of people without CVD, stable CVD, and ACS, higher BMI was associated with lower risk of death in higher risk groups. The benefits of increased body fat (i.e., increased caloric reserve) may counteract the hazards in high-risk groups, suggesting an alternative explanation of the obesity paradox.