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Reassessing the Association of Sedentary Behavior and Physical Activity with Ischemic Stroke: A Mendelian Randomization Study.
Medicine & Science in Sports & Exercise ( IF 4.1 ) Pub Date : 2024-11-18 , DOI: 10.1249/mss.0000000000003601
Yidie Lin,Xuechao Li,Meijing Hu,Jian Zhao,Cairong Zhu

PURPOSE 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). METHODS 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. RESULTS Genetic liability to leisure-time moderate-to-vigorous PA (LTMVPA) 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 (ALIC), 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. CONCLUSIONS Longer LST, less OPA and not engaging in moderate-to-vigorous PA during leisure time were associated with higher risk of ischemic stroke. The associations between PA and ischemic stroke depended on different subtypes and were mediated by changes in ALIC and cardiometabolic biomarkers.

中文翻译:


重新评估久坐行为和身体活动与缺血性中风的关系:一项孟德尔随机化研究。



目的 以前的孟德尔随机化 (MR) 研究结果与当前关于身体活动 (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) 的潜在介导作用。方法 我们使用久坐行为与 PA (n = 88,411~608,595)、心脏代谢特征 (n = 393,193~694,649)、脑 IDP (n = 33,224) 和最新的 IS 数据 (62,100 例和 1,234,808 例对照) 的全基因组关联研究的汇总统计数据进行 MR 分析。逆方差加权回归用作主要方法,并辅以多种敏感性分析。采用两步 MR 方法来评估心脏代谢特征和脑 IDP 的中介作用。结果 闲暇时间中度至强力 PA (LTMVPA) 和较高的总体 PA (OPA) 的遗传易感性与 IS 和小血管中风风险降低相关 (Benjamini-Hochberg 校正 P < 0.05)。在较长的闲暇屏幕时间与较高的 IS 风险之间以及较高的 OPA 与较低的心源性栓塞性卒中风险之间观察到提示相关性 (P < 0.05)。左内囊前肢的各向同性体积分数 (ALIC) 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 、总体光强度 PA 或总体久坐持续时间对 IS 有因果影响。结论 较长的 LST 、较少的 OPA 和闲暇时间不参与中度至剧烈的 PA 与缺血性卒中风险较高相关。 PA 与缺血性卒中之间的关联取决于不同的亚型,并由 ALIC 和心脏代谢生物标志物的变化介导。
更新日期:2024-11-18
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