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

• Published in: European heart journal Vol. 45; no. 24; pp. 2145 - 2154
• Main Authors: Lv, Yuebin, Zhang, Yue, Li, Xinwei, Gao, Xiang, Ren, Yongyong, Deng, Luojia, Xu, Lanjing, Zhou, Jinhui, Wu, Bing, Wei, Yuan, Cui, Xingyao, Xu, Zinan, Guo, Yanbo, Qiu, Yidan, Ye, Lihong, Chen, Chen, Wang, Jun, Li, Chenfeng, Luo, Yufei, Yin, Zhaoxue, Mao, Chen, Yu, Qiong, Lu, Hui, Kraus, Virginia Byers, Zeng, Yi, Tong, Shilu, Shi, Xiaoming
• Format: Journal Article
• Language: English
• Published: England 28-06-2024
• Subjects: Causal inference; Body mass index; Waist circumference; Mendelian randomization; Mortality
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehae206

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.
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.
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.
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.