A prospective Chinese Mendelian randomization study revealed that participants with higher body mass index (BMI) but lower waist circumference (WC) had the lowest mortality risk among the oldest-old. The study enrolled 5306 community-based oldest-old (mean age 90.6 years) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC for subsequent causal estimates in one-sample linear Mendelian randomization (MR) along with non-linear MR analyses. During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, both higher BMI and WC were associated with lower mortality risk [hazard ratio (HR) 0.963 for a 1-kg/m2 increment of BMI and HR 0.971 for each 5 cm increase of WC]. However, positive monotonic causal associations were observed between WC and all-cause (HR 1.108 per 5 cm increase), cardiovascular disease (CVD, HR 1.193), and non-CVD (HR 1.110) mortality, while 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) in linear MR analysis. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2. Joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. The findings are in line with some previous studies and provide additional evidence to the obesity paradox among the oldest-old. Source: https://academic.oup.com/eurheartj/
