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The association between plasma 25-hydroxyvitamin D3 concentrations, C-reactive protein levels, and coronary artery atherosclerosis in postmenopausal monkeys

Schnatz, Peter F. DO, FACOG, FACP, NCMP1,2,3,4; Vila-Wright, Sharon MD1; Jiang, Xuezhi MD1; Register, Thomas C. PhD5; Kaplan, Jay R. PhD5; Clarkson, Thomas B. DVM5; Appt, Susan E. DVM5

doi: 10.1097/gme.0b013e31825499f0
Original Articles
Editorial

Objective: The aim of this study was to identify the potential relationships between plasma 25-hydroxyvitamin D3 (25OHD3), C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets.

Methods: Female cynomolgus monkeys (n = 74) were fed a casein-lactalbumin (C/L)–based, moderately atherogenic diet for 12 months. They then consumed either a soy-based (n = 35) or C/L-based (n = 39) diet for 32 months. CRP concentrations were then determined, and monkeys underwent surgical menopause. Each diet group was then rerandomized to receive soy (n = 36) or C/L (n = 38). After 32 postmenopausal months, 25OHD3, CRP, CAA, and coronary artery remodeling were determined. All monkeys received a woman’s equivalent of 1,000 IU/day of vitamin D3 and 1,200 mg/day of calcium throughout the study.

Results: The premenopausal and postmenopausal dietary protein sources had no effect on postmenopausal 25OHD3 concentrations (P = 0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD3 concentrations and CRP at necropsy (r = −0.35, P = 0.003). A significant inverse correlation between 25OHD3 concentration and the change in CRP from premenopause to postmenopause was observed (r = −0.32, P = 0.007). The significant associations identified between plasma 25OHD3 and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling.

Conclusions: Higher plasma concentrations of 25OHD3 were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD3 concentrations are associated with an anti-inflammatory state and may support an association between oral vitamin D3 and cardioprotection.

From the Departments of 1ObGyn and 2Internal Medicine, The Reading Hospital and Medical Center; Reading, PA.; Departments of 3ObGyn and4Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; and 5Department of Pathology/Comparative Medicine, Wake Forest University; Winston-Salem, NC.

Received December 8, 2011; revised and accepted February 15, 2012.

Funding/support: The funding sources for this research and manuscript preparation were the research budgets of the Wake Forest University Primate Center and The Reading Hospital and Medical Center. In addition, the original study was supported by the following grants from the National Institutes of Health: HL079421 (J.R.K.) and PPG HL 45666 (T.B.C., J.R.K.), and AG027847 (S.E.A.).

Financial disclosure/conflicts of interest: Thomas B. Clarkson, DVM, is a member of an advisory committee to Pfizer pharmaceuticals and has been supported with a research grant from Pfizer. He is also the recipient of a research grant from Merck. The other authors have no conflicts of interest to disclose.

These data were presented in abstract form at The North American Menopause Society 22nd Annual Meeting in Washington, DC, September 22, 2011. These data and results, however, have not been published in manuscript form and have not been submitted previously to another journal.

Address correspondence to: Peter F. Schnatz, DO, The Reading Hospital and Medical Center, Department of Obstetrics and Gynecology-R1, 6th Ave & Spruce Street, West Reading, PA 19612-6052. E-mail: schnatzp@readinghospital.org

©2012The North American Menopause Society