Background:
Recent evidence suggests that racial differences in circulating levels of free or bioavailable 25(OH)D rather than total 25(OH)D may explain the apparent racial disparities in cardiovascular disease(CVD).However, few prospective studies have directly tested this hypothesis.
Objective:
Our study prospectively examined black white differences in the associations of total, free, and bioavailable 25(OH)D, vitamin D binding protein (VDBP), and parathyroid hormone (PTH) levels at baseline with incident CVD in a large, multi-ethnic, geographically diverse cohort of postmenopausal women.
Method:
We conducted a case-cohort study among 79,705 black and non-Hispanic white postmenopausal women aged 50 to 79 years and free of CVD at baseline in the Women’s Health Initiative Observational Study (WHI-OS). We included a randomly chosen subcohort of 1,300 black and 1,500 white noncases at baseline and a total of 550 black and 1,500 white women who developed incident CVD during the follow up. We directly measured circulating levels of total 25(OH)D, VDBP (monoclonal antibody assay), albumin, and PTH and calculated free and bioavailable vitamin D levels. Weighted Cox proportional hazards models were used while adjusting for known CVD risk factors.
Results:
At baseline, white women had higher mean levels of total 25(OH)D and VDBP and lower mean levels of free and bioavailable 25(OH)D and PTH than black women (all
P
values < 0.0001). White cases had lower levels of total 25(OH)D and VDBP and higher levels of PTH than white noncases, while black cases had higher levels of PTH than black noncases (all
P
values < 0.05). There was a trend toward an increased CVD risk associated with low total 25(OH)D and VDBP levels or elevated PTH levels in both US black and white women. In the multivariable analyses, the total, free, and bioavailable 25(OH)D, and VDBP were not significantly associated with CVD risk in black or white women. A statistically significant association between higher PTH levels and increased CVD risk persisted in white women, however. The multivariate-adjusted hazard ratios [HRs] comparing the extreme quartiles of PTH were 1.37 (95% CI: 1.06-1.77; P-trend=0.02) for white women and 1.12 (95% CI: 0.79-1.58; P-trend=0.37) for black women. This positive association among white women was also independent of total, free, and bioavailable 25(OH)D or VDBP. There were no significant interactions with other pre-specified factors, including BMI, season of blood draw, sunlight exposure, recreational physical activity, sitting time, or renal function.
Interpretation:
Findings from a large multiethnic case-cohort study of US black and white postmenopausal women do not support the notion that circulating levels of vitamin D biomarkers may explain black-white disparities in CVD but indicate that PTH excess may be an independent risk factor for CVD in white women.
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