Gu Xiaoxia, Du Xinchao, Yao Zhiwei, Gu Shengyuan
Department of Cardiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
Department of Thyroid Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Medicine (Baltimore). 2025 Aug 8;104(32):e43838. doi: 10.1097/MD.0000000000043838.
The relationship between statin usage and hemorrhagic stroke (HS) has been reported in clinical studies, but the link was contradictory and causality from statin usage to HS remained unclarified. We aimed to investigate statin's causal effects of blood and brain on HS risk with the Summary-data-based Mendelian randomization (SMR) method. We used 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene expression-associated single-nucleotide polymorphisms (SNPs) to proxy the pleiotropic effects of statin. Comparison analysis was performed to explore the difference between blood and the brain in the pattern of HMGCR affecting HS and HMGCR gene expression. SMR analysis found that a higher blood HMGCR expression decreased the risk of subarachnoid hemorrhage (SAH) (OR = 0.64, 95% CI = 0.43-0.95, SMR-P = .027), while brain HMGCR gene expression increased the risk of SAH at a boundary significance (OR = 1.11, 95% CI = 1.00-1.23, SMR-P = .049). Comparison analysis showed a negative relationship between blood and brain in the pattern of HMGCR affecting HS and HMGCR gene expression. This MR study suggested that HMGCR expression in the brain increased HS risk. The controversial results from the blood data were due to the difference in HMGCR gene expression between the brain and blood. Lipophilic statins might benefit patients more from the lower HS risk than the hydrophilic ones.
临床研究已报道了他汀类药物使用与出血性卒中（HS）之间的关系，但这种联系相互矛盾，他汀类药物使用与HS之间的因果关系仍不明确。我们旨在采用基于汇总数据的孟德尔随机化（SMR）方法研究他汀类药物对血液和大脑的因果效应与HS风险之间的关系。我们使用与3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）基因表达相关的单核苷酸多态性（SNP）来代表他汀类药物的多效性作用。进行比较分析以探讨HMGCR影响HS的模式以及HMGCR基因表达在血液和大脑之间的差异。SMR分析发现，血液中较高的HMGCR表达降低了蛛网膜下腔出血（SAH）的风险（OR = 0.64，95% CI = 0.43 - 0.95，SMR-P = 0.027），而大脑中HMGCR基因表达增加SAH风险，具有临界显著性（OR = 1.11，95% CI = 1.00 - 1.23，SMR-P = 0.049）。比较分析显示，在HMGCR影响HS的模式以及HMGCR基因表达方面，血液和大脑之间存在负相关关系。这项孟德尔随机化研究表明，大脑中HMGCR表达增加了HS风险。血液数据得出的有争议结果是由于大脑和血液中HMGCR基因表达的差异。亲脂性他汀类药物可能比亲水性他汀类药物在降低HS风险方面使患者受益更多。
