Genetically Determined Low‐Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage

We evaluated whether genetically elevated low‐density lipoprotein cholesterol (LDL‐C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2‐sample Mendelian randomization (MR) study. Our primary analysis used the inverse‐variance weighted method. In secondary analyses, we implemented the MR‐PRESSO method, restricted our analysis to LDL‐C–specific instruments, and performed multivariate MR. A 1‐mmol/l increase in genetically instrumented LDL‐C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73–0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL‐C levels and risk of IA/SAH. ANN NEUROL 2022;91:145–149