The Journal of clinical endocrinology and metabolism · 2025
Association of Serum 25-Hydroxyvitamin D With Stroke: Observational Mediation and Mendelian Randomization Study.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
CONTEXT: The causal association and biological mechanism linking serum 25-hydroxyvitamin D (25(OH)D) to stroke risk lacks epidemiological evidence.
OBJECTIVE: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors.
DESIGN: 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.
PATIENTS: A total of 1778 participants with serum 25(OH)D data were enrolled.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
OBJECTIVE: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors.
DESIGN: 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.
PATIENTS: A total of 1778 participants with serum 25(OH)D data were enrolled.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.