Yu-xiang Fan , Cheng-bin Yang , Zi-hao Song , Xu Yang , Yong-jie Ma , Hong-qi Zhang
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引用次数: 0
Abstract
Background
The impact of antiplatelet drugs (APDs) on the rupture risk of unruptured intracranial aneurysms (uIAs) remains controversial. This study aimed to evaluate the causal effects of APDs on aneurysmal subarachnoid hemorrhage (aSAH) and uIA.
Methods
A two-sample Mendelian randomization (TSMR) analysis examined associations between genetically proxied platelet reactivity and aSAH. The therapeutic inhibition of platelet aggregation by 5 widely used APDs was proxied by expression quantitative trait loci from eqtlGen consortium and Genotype-Tissue Expression project v8 consortium and protein quantitative trait loci from deCODE database. Causal effects were estimated with summary-data-based MR, TSMR, colocalization analysis, and sensitivity analysis. Mediation MR analysis explored potential pathways.
Results
The platelet reactivity was inversely associated with the risk of aSAH, exhibiting no discernible heterogeneity or pleiotropic effects (odds ratio, 0.883; 95% confidential interval, 0.833–0.936; P = 2.67E-05). No causal effects on the aSAH and uIA were observed for the majority of APD target genes by summary-data-based MR, TSMR, and colocalization analysis. However, elevated genetic expression of platelet endothelial aggregation receptor 1 was associated with increased platelet reactivity with an odds ratio of 1.46 (β1 = 0.375, se=0.072; P = 1.99E-07), and this elevation showed significant inverse association with aSAH risks (β2 = −0.125, se=0.030; P = 2.67E-05).
Conclusions
The platelet reactivity was inversely associated with aSAH risk. However, APDs were not identified as either risk or protective agents for aSAH or uIA. Targeting platelet endothelial aggregation receptor 1 might reduce platelet reactivity and increase aSAH risk, highlighting the need for further research.
期刊介绍:
World Neurosurgery has an open access mirror journal World Neurosurgery: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
The journal''s mission is to:
-To provide a first-class international forum and a 2-way conduit for dialogue that is relevant to neurosurgeons and providers who care for neurosurgery patients. The categories of the exchanged information include clinical and basic science, as well as global information that provide social, political, educational, economic, cultural or societal insights and knowledge that are of significance and relevance to worldwide neurosurgery patient care.
-To act as a primary intellectual catalyst for the stimulation of creativity, the creation of new knowledge, and the enhancement of quality neurosurgical care worldwide.
-To provide a forum for communication that enriches the lives of all neurosurgeons and their colleagues; and, in so doing, enriches the lives of their patients.
Topics to be addressed in World Neurosurgery include: EDUCATION, ECONOMICS, RESEARCH, POLITICS, HISTORY, CULTURE, CLINICAL SCIENCE, LABORATORY SCIENCE, TECHNOLOGY, OPERATIVE TECHNIQUES, CLINICAL IMAGES, VIDEOS