Lu Qi1, Wenjie Ma2, Yoriko Heianza2, Yan Zheng2, Tiange Wang2, Dianjianyi Sun2, Eric B Rimm2, Frank B Hu2, Edward Giovannucci2, Christine M Albert2, Kathryn M Rexrode2, JoAnn E Manson1. 1. From the Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (L.Q., Y.H., T.W., D.S.); Department of Epidemiology (L.Q., W.M., E.B.R., F.B.H., E.G., J.E.M.) and Department of Nutrition (L.Q., Y.Z., E.B.R., F.B.H., E.G.), Harvard T.H. Chan School of Public Health, Boston, MA; and Channing Division of Network Medicine (L.Q., E.B.R., F.B.H., E.G., J.E.M.) and Division of Preventive Medicine (C.M.A., K.M.R., J.E.M.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. lqil@tulane.edu jmanson@rics.bwh.harvard.edu. 2. From the Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (L.Q., Y.H., T.W., D.S.); Department of Epidemiology (L.Q., W.M., E.B.R., F.B.H., E.G., J.E.M.) and Department of Nutrition (L.Q., Y.Z., E.B.R., F.B.H., E.G.), Harvard T.H. Chan School of Public Health, Boston, MA; and Channing Division of Network Medicine (L.Q., E.B.R., F.B.H., E.G., J.E.M.) and Division of Preventive Medicine (C.M.A., K.M.R., J.E.M.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE: To comprehensively evaluate the independent associations and potential interactions of vitamin D-related biomarkers including total and bioavailable 25-hydroxyvitamin D (25OHD), VDBP (vitamin D binding protein), and parathyroid hormone (PTH) with risk of coronary heart disease (CHD). APPROACH AND RESULTS: We prospectively identified incident cases of nonfatal myocardial infarction and fatal CHD among women in the Nurses' Health Study during 20 years of follow-up (1990-2010). Using risk-set sampling, 1 to 2 matched controls were selected for each case. The analysis of 25OHD and PTH included 382 cases and 575 controls; the analysis of VDBP included 396 cases and 398 controls. After multivariate adjustment, plasma levels of total 25OHD, bioavailable 25OHD, and PTH were not significantly associated with CHD risk. VDBP was associated with a lower CHD risk with an extreme-quartile odds ratio of 0.60 (95% confidence interval, 0.39-0.92; P trend=0.02). When examining the biomarkers jointly, a significant, inverse association between 25OHD and CHD was observed among participants with higher PTH levels (P for interaction=0.02). The odds ratio (95% confidence interval) comparing the highest quartile of 25OHD to lowest was 0.43 (0.23-0.82; P trend=0.003) when PTH levels were above population median (35.3 pg/mL), whereas among the rest of participants the corresponding odds ratio (95% confidence interval) was 1.28 (0.70-2.36; P trend=0.43). CONCLUSIONS: Our data suggest that higher 25OHD levels were associated with a lower CHD risk when PTH levels were high, whereas no association was observed for participants with low PTH levels. VDBP but not bioavailable 25OHD was independently associated with lower CHD risk.
OBJECTIVE: To comprehensively evaluate the independent associations and potential interactions of vitamin D-related biomarkers including total and bioavailable 25-hydroxyvitamin D (25OHD), VDBP (vitamin D binding protein), and parathyroid hormone (PTH) with risk of coronary heart disease (CHD). APPROACH AND RESULTS: We prospectively identified incident cases of nonfatal myocardial infarction and fatal CHD among women in the Nurses' Health Study during 20 years of follow-up (1990-2010). Using risk-set sampling, 1 to 2 matched controls were selected for each case. The analysis of 25OHD and PTH included 382 cases and 575 controls; the analysis of VDBP included 396 cases and 398 controls. After multivariate adjustment, plasma levels of total 25OHD, bioavailable 25OHD, and PTH were not significantly associated with CHD risk. VDBP was associated with a lower CHD risk with an extreme-quartile odds ratio of 0.60 (95% confidence interval, 0.39-0.92; P trend=0.02). When examining the biomarkers jointly, a significant, inverse association between 25OHD and CHD was observed among participants with higher PTH levels (P for interaction=0.02). The odds ratio (95% confidence interval) comparing the highest quartile of 25OHD to lowest was 0.43 (0.23-0.82; P trend=0.003) when PTH levels were above population median (35.3 pg/mL), whereas among the rest of participants the corresponding odds ratio (95% confidence interval) was 1.28 (0.70-2.36; P trend=0.43). CONCLUSIONS: Our data suggest that higher 25OHD levels were associated with a lower CHD risk when PTH levels were high, whereas no association was observed for participants with low PTH levels. VDBP but not bioavailable 25OHD was independently associated with lower CHD risk.
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