Identification of a mechanism for increased cardiovascular risk among individuals with low vitamin D concentrations

Objective: The aim of this study was to investigate the plasma concentrations of vitamin D and its association with plasma lipid profiles. Methods: Plasma vitamin D3 and lipid concentrations were measured in 119 female cynomolgus monkeys (premenopausal, n = 49; ovariectomized, n = 70) consuming approximately 1,000 IU per day of vitamin D ₃. In a subset of the ovariectomized monkeys (n = 23), vitamin D ₃ was remeasured after 6 months. The concentrations of vitamin D ₃ were analyzed as a continuous variable and were divided at the median into high (≥48 ng/mL) versus low (<48 ng/mL) groupings. Results: Among the 119 monkeys, the range of vitamin D ₃ concentrations was 24.0 to 95.2 ng/mL (mean ± SD, 48.5 ± 12.7 ng/mL). Plasma vitamin D ₃ concentration was positively associated with high-density lipoprotein cholesterol (HDL-C; P = 0.003). Monkeys in the high vitamin D ₃ group had a significantly greater plasma HDL-C concentration (57.9 mg/dL) than did those in the low vitamin D ₃ group (47.1 mg/dL; P = 0.001). Although the difference was not significant (P = 0.120), the monkeys in the high vitamin D ₃ group had a decreased total plasma cholesterol-to-HDL-C ratio compared with those in the low vitamin D3 group (5.4 and 6.2, respectively), potentially putting them at lower risk of atherosclerosis development. Conclusions: Given that the monkeys all consumed a diet replete in vitamin D ₃, it seems that individual differences in vitamin D absorption or metabolism may have determined whether the monkeys had high or low concentrations of vitamin D ₃. Lower vitamin D ₃ was associated with a more atherogenic lipid profile, a major risk factor for progressing to coronary artery atherosclerosis in monkeys and human beings.