Racial/Ethnic Differences in 25-Hydroxy Vitamin D and Parathyroid Hormone Levels and Cardiovascular Disease Risk Among Postmenopausal Women

Abstract

Background Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25-hydroxy vitamin D (25[ OH ]D) rather than total 25( OH )D may explain apparent racial disparities in cardiovascular disease ( CVD ). We prospectively examined black-white differences in the associations of total, free, and bioavailable 25( OH )D, vitamin D-binding protein, and parathyroid hormone levels at baseline with incident CVD (including nonfatal myocardial infarction, nonfatal stroke, and CVD death) in postmenopausal women. Methods and Results We conducted a case-cohort study among 79 705 postmenopausal women, aged 50 to 79 years, who were free of CVD at baseline in the WHI-OS (Women's Health Initiative Observational Study). A subcohort of 1300 black and 1500 white participants were randomly chosen as controls; a total of 550 black and 1500 white women who developed incident CVD during a mean follow-up of 11 years were chosen as cases. We directly measured total 25( OH )D, vitamin D-binding protein, albumin, parathyroid hormone, and calculated free and bioavailable 25( OH )D. Weighted Cox proportional hazards models were used to examine their associations with CVD risk. Although vitamin D-binding protein and total, free, and bioavailable 25( OH )D were not significantly associated with CVD risk in black or white women, a significant positive association between parathyroid hormone and CVD risk persisted in white women (hazard ratio comparing the highest quartile with the lowest, 1.37; 95% CI , 1.06-1.77) but not in black women (hazard ratio comparing the highest quartile with the lowest, 1.12; 95% CI, 0.79-1.58), independent of total, free, and bioavailable 25( OH )D or vitamin D-binding protein. Conclusions Circulating levels of vitamin D biomarkers are not related to CVD risk in either white or black women. Higher parathyroid hormone levels may be an independent risk factor for CVD in white women.

Keywords: 25(OH)D; biomarker; cardiovascular disease; parathyroid hormone/calcitonin; vitamin D; women.

Figure 1

Race/ethnicity‐specific associations of total 25‐hydroxy vitamin D (25[OH]D) and parathyroid hormone (PTH) with cardiovascular disease (CVD) events. A, Total 25(OH)D and CVD events. B, PTH and CVD events. Associations were estimated by proportional hazards regression–based restricted cubic spline analyses among white and black women, separately. We calculated restricted cubic spline with 3 fixed knots at 10%, 50%, and 90% percentiles based on the distribution of each biomarker level. Solid lines with gray areas indicate the hazard ratios (HRs) and 95% CIs. The model was adjusted for age, clinical center, race/ethnicity, body mass index, family history of CVD, educational levels, alcohol intake, physical activity levels, cigarette smoking status, postmenopausal hormone therapy use, estimated glomerular filtration rate, and season of blood draw.