Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.,International Journal of Epidemiology

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Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.
International Journal of Epidemiology ( IF 6.4 ) Pub Date : 2024-08-14 , DOI: 10.1093/ije/dyae125
Andri Iona,Fiona Bragg,Zammy Fairhurst-Hunter,Iona Y Millwood,Neil Wright,Kuang Lin,Ling Yang,Huaidong Du,Yiping Chen,Pei Pei,Liang Cheng,Dan Schmidt,Daniel Avery,Canqing Yu,Jun Lv,Robert Clarke,Robin Walters,Liming Li,Sarah Parish,Zhengming Chen,

BACKGROUND Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. METHODS The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79 years in 2004-08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12 years of follow-up. RESULTS Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41-1.58), 1.49 (1.38-1.61), 1.42 (1.31-1.54) and 1.64 (1.58-1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20-1.23), 1.28 (1.26-1.29), 1.31 (1.29-1.33) and 1.14 (1.10-1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. CONCLUSIONS Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.

更新日期：2024-08-14

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