To analyze vitamin D3 plasma concentrations among monkeys randomized to oral conjugated equine estrogen (CEE) versus control and the association with coronary artery atherosclerosis (CAA).
Surgically postmenopausal monkeys (N = 50) were fed an atherogenic diet containing a woman's equivalent of 1000 IU/day of vitamin D3. The monkeys were randomized at baseline to receive CEE (equivalent of 0.45 mg/d, n = 25) or placebo (n = 25). 25-hydroxyvitamin D3 (25OHD3) was measured at baseline and 20 months later. At 20 months, CAA evidence of coronary artery remodeling, and American Heart Association (AHA) severity scores were assessed.
The percent change in 25OHD3 concentrations from baseline to 20 months postrandomization was inversely correlated with plaque area of the right coronary artery (P = 0.048), left circumflex artery (P = 0.039), left anterior descending artery (P = 0.017), and AHA severity score (AHA LADmax) (P = 0.016). Those with increased 25OHD3 concentrations who were taking CEE also had significantly lower AHA scores compared with those who were not taking CEE and did not have an increase in 25OHD3 (P = 0.01).
Monkeys with increases in 25OHD3 concentrations had significantly less severe CAA. Those with increases in 25OHD3 with CEE were associated with significantly decreased AHA lesion scores, decreased plaque, and greater coronary artery remodeling. If these findings are present in women, achieving higher 25OHD3 concentrations (or being a vitamin D supplementation “responder”) may be associated with cardioprotection, and further studies to evaluate a synergistic effect with CEE and vitamin D on cardiovascular health are needed.
1Department of ObGyn
2Department of Internal Medicine, Reading Hospital, Reading, PA
3Department of ObGyn
4Department of Internal Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
5Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
Address correspondence to: Peter F. Schnatz, DO, FACOG, FACP, NCMP, Associate Chairman and Residency Program Director, Department of ObGyn, Reading Hospital, R1, P.O. Box 16052, Reading, PA 19612-6052. E-mail: Peter.Schnatz@readinghealth.org
Received 31 July, 2015
Revised 21 October, 2015
Accepted 21 October, 2015
The contents are solely the responsibility of the authors and do not necessarily represent the view of Pfizer.
Funding/support: This study was supported by grants from Pfizer, Inc. (an investigator-initiated grant to Wake Forest School of Medicine; principal investigator, TBC). Wake Forest School of Medicine has received an investigator-initiated (TBC) grant (bazedoxifene acetate) from Pfizer. TBC was a paid co-investigator and has been a consultant for Pfizer.
Financial disclosure/conflicts of interest: TBC, DVM, was the recipient of a research grant from Merck and during this research was the recipient of a research grant from Pfizer. The other authors have no conflicts of interest.