Lin Yidie, Li Xuechao, Hu Meijing, Zhao Jian, Zhu Cairong
Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, CHINA.
Med Sci Sports Exerc. 2025 Apr 1;57(4):781-790. doi: 10.1249/MSS.0000000000003601. Epub 2024 Nov 18.
Findings from previous Mendelian randomization (MR) studies disagreed with the current scientific consensus regarding the role of physical activity (PA) and sedentary behavior in ischemic stroke (IS). We reassessed these associations with a focus on etiological subtypes of IS and the potential mediating roles of cardiometabolic traits and brain imaging-derived phenotypes (IDPs).
We performed MR analyses using summary statistics from genome-wide association studies of sedentary behavior and PA ( n = 88,411 ~ 608,595), cardiometabolic traits ( n = 393,193 ~ 694,649), brain IDPs ( n = 33,224), and the latest IS data (62,100 cases and 1,234,808 controls). Inverse-variance weighted regression was used as the primary method, complemented by several sensitivity analyses. A two-step MR approach was employed to assess the mediating effects of cardiometabolic traits and brain IDPs.
Genetic liability to leisure-time moderate-to-vigorous PA (MVPA) and higher overall PA (OPA) were associated with reduced risks of IS and small vessel stroke (Benjamini-Hochberg adjusted P < 0.05). Suggestive associations were observed between longer leisure-screen time and higher IS risk and between higher OPA and lower cardioembolic stroke risk ( P < 0.05). The isotropic volume fraction in the anterior limb of the left internal capsule, as well as some cardiometabolic metrics, partially mediated these associations. There was no evidence for causal effects of overall MVPA, overall light-intensity PA, or overall sedentary duration on IS.
Longer leisure screen time, less OPA, and not engaging in MVPA during leisure time were associated with higher risk of IS. The associations between PA and IS depended on different subtypes and were mediated by changes in anterior limb of the left internal capsule and cardiometabolic biomarkers.
先前孟德尔随机化（MR）研究的结果与当前关于体力活动（PA）和久坐行为在缺血性中风（IS）中的作用的科学共识不一致。我们重新评估了这些关联，重点关注IS的病因亚型以及心脏代谢特征和脑成像衍生表型（IDP）的潜在中介作用。
我们使用来自久坐行为和PA（n = 88,411608,595）、心脏代谢特征（n = 393,193694,649）、脑IDP（n = 33,224）的全基因组关联研究的汇总统计数据以及最新的IS数据（62,100例病例和1,234,808例对照）进行MR分析。采用逆方差加权回归作为主要方法，并辅以多种敏感性分析。采用两步MR方法评估心脏代谢特征和脑IDP的中介作用。
休闲时中度至剧烈PA（MVPA）的遗传易感性和较高的总体PA（OPA）与IS和小血管中风风险降低相关（Benjamini-Hochberg校正P<0.05）。观察到休闲屏幕时间较长与较高的IS风险之间以及较高的OPA与较低的心源性栓塞性中风风险之间存在提示性关联（P<0.05）。左侧内囊前肢的各向同性体积分数以及一些心脏代谢指标部分介导了这些关联。没有证据表明总体MVPA、总体低强度PA或总体久坐时间对IS有因果影响。
休闲屏幕时间较长、OPA较少以及休闲时不进行MVPA与较高的IS风险相关。PA与IS之间的关联取决于不同的亚型，并由左侧内囊前肢的变化和心脏代谢生物标志物介导。
