医学
腔隙性中风
冲程(发动机)
血栓形成
疾病
心脏病学
颅内血栓形成
血管疾病
卡德西尔
内科学
缺血性中风
缺血
静脉血栓形成
痴呆
机械工程
工程类
作者
Fatemeh Koohi,Eric L. Harshfield,Aleksey Shatunov,Hugh S. Markus
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2024-04-01
卷期号:55 (4): 934-942
标识
DOI:10.1161/strokeaha.123.044937
摘要
BACKGROUND: The importance of thromboembolism in the pathogenesis of lacunar stroke (LS), resulting from cerebral small vessel disease (cSVD), is debated, and although antiplatelets are widely used in secondary prevention after LS, there is limited trial evidence from well-subtyped patients to support this approach. We sought to evaluate whether altered anticoagulation plays a causal role in LS and cSVD using 2-sample Mendelian randomization. METHODS: From a recent genome-wide association study (n=81 190), we used 119 genetic variants associated with venous thrombosis at genome-wide significance ( P <5*10 −8 ) and with a linkage disequilibrium r 2 <0.001 as instrumental variables. We also used genetic associations with stroke from the GIGASTROKE consortium (62 100 ischemic stroke cases: 10 804 cardioembolic stroke, 6399 large-artery stroke, and 6811 LS). In view of the lower specificity for LS with the CT-based phenotyping mainly used in GIGASTROKE, we also used data from patients with magnetic resonance imaging–confirmed LS (n=3199). We also investigated associations with more chronic magnetic resonance imaging features of cSVD, namely, white matter hyperintensities (n=37 355) and diffusion tensor imaging metrics (n=36 533). RESULTS: Mendelian randomization analyses showed that genetic predisposition to venous thrombosis was associated with an increased odds of any ischemic stroke (odds ratio [OR], 1.19 [95% CI, 1.13–1.26]), cardioembolic stroke (OR, 1.32 [95% CI, 1.21–1.45]), and large-artery stroke (OR, 1.41 [95% CI, 1.26–1.57]) but not with LS (OR, 1.07 [95% CI, 0.99–1.17]) in GIGASTROKE. Similar results were found for magnetic resonance imaging–confirmed LS (OR, 0.94 [95% CI, 0.81–1.09]). Genetically predicted risk of venous thrombosis was not associated with imaging markers of cSVD. CONCLUSIONS: These findings suggest that altered thrombosis plays a role in the risk of cardioembolic and large-artery stroke but is not a causal risk factor for LS or imaging markers of cSVD. This raises the possibility that antithrombotic medication may be less effective in cSVD and underscores the necessity for further trials in well-subtyped cohorts with LS to evaluate the efficacy of different antithrombotic regimens in LS.
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