Association Between Arterial Stiffness Index and Age-Related Diseases: A Mendelian Randomization Study

Arterial stiffness is an emerging indicator of cardiovascular risk, but its causal relationship with a variety of age-related diseases is unclear. The objective is to assess the causal relationship between arterial stiffness index (ASI) and age-related diseases by Mendelian randomization (MR) analysis. We obtained instrumental variables associated with age-related diseases from genome-wide association studies (GWAS) of 484,598 European individuals, and data for ASI were obtained from the UK Biobank GWAS of 127,127 participants. We used the inverse variance-weighted as the primary analysis method. In addition, several sensitivity analyses including MR-Egger, weighted-median (WM), Mendelian randomization pleiotropy residual sum and outlier, and Cochran's Q test were performed to test the robustness of the results. Reverse MR analysis was also performed to assess reverse causal relationships between age-related diseases and ASI. We verified the causal relationship between eight age-related diseases and ASI, of which cardiovascular disease (β = 0.19), gallbladder disease (β = 0.85), liver, biliary, or pancreas problem (β = 1.02), hypertension (β = 0.19), joint disorder (β = 0.53), and esophageal disorder (β = 2.10) elevated ASI. In contrast, hyperthyroidism or thyrotoxicosis (β = -2.17) and bowel problems (β = -1.83) may reduce ASI. This MR analysis reveals causal relationships between ASI and several age-related diseases. ASI is expected to be a potential indicator of health conditions for older populations.