LAUSR

OBJECTIVE 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). METHODS We conducted a two-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 multivariable MR. RESULTS One mmol/L increase of genetically-instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (OR=0.83; 95%CI=0.73-0.94; p=0.004). Results remained consistent in secondary and multivariable analyses (all p<0.05). INTERPRETATION Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. This article is protected by copyright. All rights reserved.