AS325 - Racial/ethnic differences in 25(OH)D and PTH levels and CVD among women

Investigator Names and Contact Information

Yiqing Song (yiqsong@iu.edu)

Introduction/Intent

Emerging evidence-based dietary guidelines on vitamin D and its health effects are largely based on bone health. Further research is urgently needed to clarify the optimal levels of vitamin D for nonskeletal outcomes, including cardiovascular disease (CVD). Observational and clinical studies have shown that low vitamin D and high parathyroid hormone (PTH), jointly or independently, are related to the risk of cardiovascular disease (CVD) and may operate through multiple shared pathways. Nevertheless, sparse data are available to fully address ethnic differences in levels of 25-hydroxyvitamin D [25(OH)D] and PTH in relation to CVD risk. The Women’s Health Initiative (WHI) provides an exceptional opportunity to examine comprehensively the association of vitamin D status and CVD risk among women of diverse race/ethnicity, and to assess the extent to which vitamin D insufficiency may explain health disparities by race. We propose to conduct a case-cohort study in the WHI-observational study (WHI-OS), to assess racial/ethnic disparities in the prospective associations of 25(OH)D and PTH levels with major cardiovascular events (a composite of nonfatal myocardial infarction [MI], stroke, and CVD mortality). We will include all incident CVD cases in black women (N=550) and a random sample of incident CVD cases from American white women (N=2,000). Noncases will be drawn from a random subcohort of white and black women in the WHI-OS. To assess racial/ethnic differences in baseline 25(OH)D and PTH levels in the entire multiethnic WHI cohort, we will supplement the random subcohort with a random sample of postmenopausal women of other races/ethnicities (total N~4,400). In addition, we will identify whether 25(OH)D and PTH levels correlate with intermediate CVD phenotypes from available data (including measured systolic and diastolic blood pressure, lipids, CRP, IL-6, TNFa, sICAM, IL-1, E-selectin, fasting glucose and insulin, and calculated HOMA indices). In summary, the WHI-OS, as one of the largest most ethnically diverse cohorts of postmenopausal women with abundant health information on CVD risk factors and outcomes, will offer us a unique cost-effective opportunity to answer important and timely questions about ethnicity-specific cutoff values of 25(OH)D defining vitamin D insufficiency or deficiency as well as ethnic disparity in the relation of vitamin D and CVD.

Specific Aims

Primary aims:

In a case-cohort design in the WHI-OS:

1. To test whether 25(OH)D or PTH levels predict the risk of major CVD events (a composite endpoint of nonfatal MI, nonfatal stroke, and CVD mortality) and explore possible threshold levels of 25(OH)D associated with CVD in U.S. non-Hispanic white and black women.
2. To test whether white-black disparities in CVD risk can be explained by differences in levels of 25(OH)D or PTH.

In a random sample of postmenopausal women in the entire WHI-OS cohort (N=~4,400):

1. To assess racial/ethnic disparities in levels of 25(OH)D and investigate the prevalence of vitamin D insufficiency or deficiency in an ethnicity-specific manner.
2. To explore racial/ethnic disparities in levels of PTH and comprehensively assess potential determinants of PTH variation (excluding women with primary or secondary hyperparathyroidism).

Secondary aims (case-cohort study):

1. To test whether 25(OH)D or PTH levels predict the risk of CHD (nonfatal MI + CHD death), stroke, and CVD mortality (as individual outcomes) in American white and black women.

2. To test whether white-black disparities in each major CVD outcome (individually) can be explained by differences in levels of 25(OH)D or PTH.

   Tertiary aims (among all study participants with available data):

3. To test whether levels of 25(OH)D or PTH are associated with intermediate CVD phenotypes including measured systolic and diastolic blood pressure, lipids, CRP, IL-6, TNFa, sICAM, IL1, E-selectin, fasting glucose and insulin, and HOMA indices.

4. To test whether racial/ethnic differences in intermediate CVD phenotypes can be explained by differences in levels of 25(OH)D or PTH.

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Results/ Findings

A complete list of WHI papers is available in the Papers section of this website.