How does obesity affect mortality through blood pressure and blood glucose in Chinese and US citizens? Insights from a causal mediation analysis of two large cohorts

BACKGROUND: Obesity, which has reached the scale of a global pandemic, is a leading cause of premature death. It is unclear to what extent its effect on mortality was driven by blood pressure or glucose levels in people of different ethnicities. METHODS: We conducted a causal mediation analysis to estimate the mediation effect of blood pressure and glucose between body mass index (BMI) or waist-hip ratio (WHR) on mortality based on data from the China Kadoorie Biobank (CKB) (n = 458 385) and US National Health and Nutrition Examination Survey (NHANES) (1999-2008, n = 20 726). RESULTS: The WHR's effect on mortality was mediated by blood pressure and glucose in the CKB data set by 38.7% (95% confidence interval (CI) = 34.1, 43.2) and 36.4% (95% CI = 31.6, 42.8), whereas in NHANES by 6.0% (95% CI = 2.3, 8.3) and 11.2% (95% CI = 4.7, 22.7), respectively. For associations between BMI and mortality in subjects with overweight or obesity, the mediator proportion of blood pressure and glucose was 49.4% (95% CI = 40.1, 62.5) and 16.9% (95% CI = 13.6, 22.9) in CKB and 9.10% (95% CI = 2.2, 25.9) and 16.7% (95% CI = 7.3, 49.0) in NHANES, respectively. We stratified the patients by their blood glucose, blood pressure level, or both into four groups. The effect of WHR on mortality was comparable across subgroups in either cohort. The associations between BMI and mortality were stronger in patients with higher blood pressure in CKB (P = 0.011) and blood glucose in NHANES (P = 0.035) in patients with overweight and obesity. CONCLUSIONS: The relationship between WHR and mortality in the CKB data set was potentially caused by blood pressure and glucose to a much greater extent than in the NHANES one. The effect of BMI influenced by blood pressure was significantly higher among Chinese individuals with overweight and obesity. These results implicate a different intervention strategy is required for blood pressure and blood glucose in China and US to prevent obesity and obesity-related premature death.