BACKGROUND: Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation. METHODS: Plasma concentrations of 25-hydroxyvitamin D(3) were determined by radioimmunoassay in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4+/-6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation. RESULTS: On univariate analyses, low 25-hydroxyvitamin D(3) levels were inversely correlated with asymmetric dimethylarginine concentrations, high-sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D(3) levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D(3) levels. On multiple linear analysis, both asymmetric dimethylarginine (beta=-0.19, P=.003) and high-sensitivity C-reactive protein (beta=-0.14, P=.03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations; other significant correlates were male gender (beta=0.19, P=.003), calcium levels (beta=0.14, P=.03), and use of angiotensin-converting enzyme inhibitor (beta=-0.17, P=.007). CONCLUSION: Low 25-hydroxyvitamin D(3) levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk. ; http://www.elsevier.com/wps/find/journaldescription.cws_home/525049/description#description ; Doan T. Ngo, Aaron L. Sverdlov, John J. McNeil, and John D. Horowitz