Circulating 25OHD, Dietary Vitamin D, PTH, and Calcium Associations with Incident Cardiovascular Disease and Mortality: The MIDSPAN Family Study

CONTEXT: Observational studies relating circulating 25-hydroxyvitamin D (25OHD) and dietary vitamin D intake to cardiovascular disease (CVD) have reported conflicting results. OBJECTIVE: Our objective was to investigate the association of 25OHD, dietary vitamin D, PTH, and adjusted calcium with CVD and mortality in a Scottish cohort. DESIGN AND SETTING: The MIDSPAN Family Study is a prospective study of 1040 men and 1298 women from the West of Scotland recruited in 1996 and followed up for a median 14.4 yr. PARTICIPANTS: Locally resident adult offspring of a general population cohort were recruited from 1972-1976. MAIN OUTCOME MEASURES: CVD events (n = 416) and all-cause mortality (n = 100) were evaluated. RESULTS: 25OHD was measured using liquid chromatography-tandem mass spectrometry in available plasma (n = 2081). Median plasma 25OHD was 18.6 ng/ml, and median vitamin D intake was 3.2 μg/d (128 IU/d). Vitamin D deficiency (25OHD <15 ng/ml) was present in 689 participants (33.1%). There was no evidence that dietary vitamin D intake, PTH, or adjusted calcium were associated with CVD events or with mortality. Vitamin D deficiency was not associated with CVD (fully adjusted hazard ratio = 1.00; 95% confidence interval = 0.77-1.31). Results were similar after excluding patients who reported an activity-limiting longstanding illness at baseline (18.8%) and those taking any vitamin supplements (21.7%). However, there was some evidence vitamin D deficiency was associated with all-cause mortality (fully adjusted hazard ratio = 2.02; 95% confidence interval = 1.17-3.51). CONCLUSION: Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD. Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD.