Causal Effect of 25-Hydroxyvitamin D3 on Hypertension and Mediation by High-Sensitivity C-Reactive Protein: A Mendelian Randomization Study

Abstract OBJECTIVE To investigate the independent causal relationship between 25-hydroxyvitamin D3 [25(OH)D3] and hypertension and to assess the mediating role of high-sensitivity C-reactive protein (hsCRP) in this relationship. METHODS Statistical data from genome-wide association studies were collected, and a two-sample Mendelian randomization (TSMR) analysis was performed to test the causal association between 25(OH)D3 and hypertension. Additionally, a two-step mediation analysis was conducted to explore whether the potential association between 25(OH)D3 and hypertension was partially mediated through hsCRP. RESULTS The TSMR analysis showed that increased levels of 25(OH)D3 lowered the risk of hypertension (odds ratio [OR] = 0.975, 95% confidence interval [CI]: 0.960–0.990, P = .001). Additionally, 25(OH)D3 was negatively associated with hsCRP (OR = 0.945, 95% CI: 0.911–0.980, P = .002), and hsCRP was positively associated with hypertension (OR = 1.018, 95% CI: 1.012–1.025, P = .001). The mediation analysis further confirmed that hsCRP mediates the effect of 25(OH)D3 on hypertension risk, with an effect value of −0.001 (95% CI: −0.002 to 0). CONCLUSIONS A causal relationship exists between 25(OH)D3 and hypertension, with hsCRP mediating this association.