Vitamin D, Hypertension, and Ischemic Stroke in 116 655 Individuals From the General Population A Genetic Study

Observational studies indicate that low concentrations of plasma 25-hydroxyvitamin D (25(OH) D) are associated with high blood pressure, hypertension, and ischemic stroke. However, whether these associations are causal remain unknown. A total of 116 655 white individuals of Danish descent from the general population were genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25(OH) D concentrations; 35 517 had plasma 25(OH) D measurements. Primary outcomes were blood pressure, hypertension, and ischemic stroke. Median follow-up for incident ischemic stroke was 9.3 years (range, 1 day-33.6 years). DHCR7/CYP2R1 allele score was as expected associated with lower 25(OH) D concentration (F=328 and R-2=1.0%). A genetically determined 10 nmol/L lower 25(OH) D concentration was associated with a 0.68 (95% confidence interval [CI], 0.20-1.17) mm Hg higher systolic blood pressure and a 0.36 (95% CI, 0.08-0.63) mm Hg higher diastolic blood pressure with corresponding observational estimates of 0.58 (95% CI, 0.50-0.68) and 0.40 (95% CI, 0.35-0.45) mm Hg. The odds ratio for hypertension was 1.02 (95% CI, 0.97-1.08) for a genetically determined 10 nmol/L lower 25(OH) D with a corresponding observational odds ratio of 1.06 (95% CI, 1.05-1.07). The odds ratio for ischemic stroke was 0.98 (95% CI, 0.86-1.13) for a genetically determined 10 nmol/L decrease in 25(OH) D with a corresponding observational odds ratio of 1.03 (95% CI, 1.01-1.05). Genetic and observational low 25(OH) D concentrations were associated with higher blood pressure, as well as with hypertension consistent with causal relationships. Because observational but not genetic low 25(OH) D concentration was associated with ischemic stroke, and as the CIs overlapped, we can neither support nor exclude a causal relationship.