Association between Lipid-Lowering Drugs and Traumatic Subdural Hemorrhage: A Mendelian Randomization Study

Abstract

Background: There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, Proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors and Niemann-Pick C1-like protein 1 (NPC1L1) inhibitors on traumatic subdural hematomas. Methods: We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study. Results: A causal relationship was found between HMGCR inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = –0.7593341 (Odds Ratio (OR) = 0.4679779), p = 0.008366947 < 0.05)). However, no causal relationship was found between PCSK9 inhibitors and NPC1L1 inhibitors and traumatic subdural hematoma (PCSK9 inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), p = 0.1126327), NPC1L1 inhibitors: Inverse variance weighted (β = –0.02118558 (OR = 0.9790373), p = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results. Conclusions: This two-sample MR study suggests a potential causal relationship between HMGCR inhibition (atorvastatin) and traumatic subdural hemorrhage.

Keywords

• lipid-lowering drugs
• traumatic subdural hemorrhage
• mendelian randomization analysis
• cause-and-effect relationship
• drug targeting