Are Vitamin D Deficiency and VDR Gene Polymorphisms Associated With Higher Blood Pressure Defined by the 2017 ACC/AHA in Postmenopausal Women?

Abstract Postmenopausal status has been associated with an unfavorable phenotype tied to hormonal and metabolic changes, which collectively could contribute to an increased risk of cardiovascular disease. Vitamin D deficiency is frequent in postmenopausal women and may be linked to this phenotype and especially to an increased risk of developing hypertension. Vitamin D actions are modulated by the vitamin D receptor (VDR), and metabolic abnormalities have been associated with VDR gene variants in different populations. The aims of the present study were to assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension by the 2017 ACC/AHA definition in postmenopausal women. We conducted a cross-sectional study of biobanked blood samples from 339 postmenopausal women with no evidence of clinical disease. Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR with allelic discrimination assays. Mean serum total 25(OH)D levels were 22.99±8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p=0.014) and free 25(OH)D levels (p=0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. The CC+CT genotypes of Bsm-I and the AA+AG genotypes of Taq-I polymorphisms were more frequent in women with stage 2 hypertension (Bsm-I CC+CT: 85.8% vs. TT: 14.2%, p=0.045; Taq-I AA+AG: 91.3% vs. GG: 8.7%, p=0.021). A higher prevalence ratio of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p<0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p<0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p=0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p=0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these analyses lost significance when adjusted for age and BMI. In conclusion, the present results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.