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Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study

2024; Oxford University Press; Volume: 45; Issue: 24 Linguagem: Inglês

10.1093/eurheartj/ehae206

1522-9645

Yuebin Lv, Yue Zhang, Xinwei Li, Xiang Gao, Yongyong Ren, Luojia Deng, Lanjing Xu, Jinhui Zhou, Bing Wu, Wei Yuan, Xingyao Cui, Zinan Xu, Yanbo Guo, Yidan Qiu, Li-Hong Ye, Chen Chen, Jun Wang, Ming C. Lin, Yufei Luo, Zhaoxue Yin, Chen Mao, Qiong Yu, Hui Lü, Virginia B. Kraus, Yi Zeng, Shilu Tong, Xiaoming Shi,

Genetic Associations and Epidemiology

Abstract Background and Aims Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. Methods A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. Results During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955–0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950–0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928–0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036–1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064–1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016–1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. Conclusions Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.