Tsai Ming-Chieh, Fan Hsien-Yu, Hsu Hsin-Yin, Tseng Po-Jung, Chuang Shih-Ming, Yeh Tzu-Lin, Lee Chun-Chuan, Chien Ming-Nan, Chien Kuo-Liong
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan.
J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1420-e1429. doi: 10.1210/clinem/dgae561.
The causal association and biological mechanism linking serum 25-hydroxyvitamin D (25(OH)D) to stroke risk lacks epidemiological evidence.
This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors.
The community-based prospective community-based cohort study, the Chin-Shan Community Cardiovascular Cohort, was conducted from 1990 to December 2011, with external validation using a 2-sample Mendelian randomization (MR) study.
A total of 1778 participants with serum 25(OH)D data were enrolled.
In the Chin-Shan Community Cardiovascular Cohort observational study, the outcome was ascertained as stroke, while in the 2-sample MR study, it was defined as ischemic stroke. Causal effects were estimated using restricted cubic spline analysis, COX proportional hazard ratios, mediation analysis, and 2-sample MR.
Over 12 years (21 598 person-years) of follow-up, 163 participants (9.17%) developed stroke. Higher 25(OH)D concentrations were associated with lower stroke risk (hazard ratio: 0.64; 95% confidence interval, 0.43-0.96) after full-model adjustments. Mediation analysis showed a significant association between 25(OH)D concentration and stroke risk mediated by hypertension in unadjusted models (mediation percentage 23.3%, P = .008) that became nonsignificant in full models (mediation percentage, 15.5%; P = .072). Two-sample MR confirmed a significant inverse association between genetically determined 25(OH)D and stroke risk (inverse variance weighted method odds ratio 0.92; 95% confidence interval: 0.85-0.99; P = .036). However, hypertension had an insignificant mediating role in the MR study.
Higher 25(OH)D levels are linked to reduced stroke risk, potentially mediated by hypertension. Prioritizing blood pressure management may improve stroke prevention in 25(OH)D-deficient patients.
血清25-羟维生素D（25(OH)D）与中风风险之间的因果关联及生物学机制缺乏流行病学证据。
本研究旨在调查25(OH)D浓度与中风风险之间的关联以及潜在的中介因素。
基于社区的前瞻性队列研究——金山社区心血管队列研究，于1990年至2011年12月进行，并采用两样本孟德尔随机化（MR）研究进行外部验证。
共纳入1778名有血清25(OH)D数据的参与者。
在金山社区心血管队列观察性研究中，结局确定为中风，而在两样本MR研究中，结局定义为缺血性中风。使用受限立方样条分析、COX比例风险比、中介分析和两样本MR估计因果效应。
经过12年（21598人年）的随访，163名参与者（9.17%）发生中风。在全模型调整后，较高的25(OH)D浓度与较低的中风风险相关（风险比：0.64；95%置信区间，0.43 - 0.96）。中介分析显示，在未调整模型中，25(OH)D浓度与由高血压介导的中风风险之间存在显著关联（中介百分比23.3%，P = 0.008），在全模型中该关联变得不显著（中介百分比，15.5%；P = 0.072）。两样本MR证实，基因决定的25(OH)D与中风风险之间存在显著的负相关（逆方差加权法优势比0.92；95%置信区间：0.85 - 0.99；P = 0.036）。然而，在MR研究中，高血压的中介作用不显著。
较高的25(OH)D水平与降低中风风险相关，可能由高血压介导。优先进行血压管理可能会改善25(OH)D缺乏患者的中风预防。
