The association of arterial stiffness index with cerebrovascular and cardiometabolic disease: A Mendelian randomization study

Background: Arterial stiffness index (ASI) is a potential risk factor for cerebrovascular and cardiometabolic diseases, but the causal links between them are inconclusive. The aim is to evaluate the causal effects of ASI on cerebrovascular and cardiometabolic diseases by Mendelian randomization (MR). Methods: Two-sample MR analysis was performed to infer causal links. Genetic variants significantly associated with ASI were extracted. The inverse variance weighted method was used for estimating the effects. Sensitivity analysis was performed to test heterogeneity or pleiotropy. Results: MR analysis indicated an effect of genetically predicted ASI on the risk of ischemic stroke (IS) of all causes (OR = 1.894, 95% CI 1.210-2.965, p = 0.005). No links were identified between genetically predicted ASI and other cerebrovascular or cardiometabolic diseases (all p > 0.05). Subgroup analysis of IS etiologies found a suggestive association between genetically predicted ASI and large artery atherosclerosis stroke (LAS) (OR = 3.726, 95% CI 1.230-11.286, p = 0.020). There were no effects of ASI on IS due to cardioembolism or small vessel occlusion. Conclusion: The current MR analysis suggested that genetically predicted ASI was associated with higher risk of IS of all causes. The results and the underlying pathways or mechanisms between ASI and IS needs further investigation.

Automated summary

This study used Mendelian randomization to analyze the causal effects of arterial stiffness index (ASI) on cerebrovascular and cardiometabolic diseases. The results indicated that genetically predicted ASI was associated with a higher risk of ischemic stroke (IS) of all causes, but no clear links were found with other cerebrovascular or cardiometabolic diseases. Subgroup analysis suggested an association between genetically predicted ASI and large artery atherosclerosis stroke (LAS).