Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

Background: Antihypertensive and tissue-protective properties of vitamin D metabolites are increasingly attributed to the inhibition of renin synthesis by 1.25-dihydroxyvitamin [1,25(OH)2D] in the kidney. Method: We aimed to document a potential association between 25-hydroxyvitamin D [25(OH)D], 1.25(OH) 2D and the circulating renin-angiotensin system (RAS) in a large cohort of patients referred (n=3316) to coronary angiography. |Results: Of the 3316 subjects, 3296 (median age: 63.5 (56.3-70.6)years; 30.2% women) had a baseline measurement of 25(OH)D [median: 15.6(10.1-23.0)mu g/L, 1,25(OH)2D [median: 33.2(25.2-42.9) pg/mLJ, plasma renin concentration [PRC; median: 11.4(6.0-24.6)pg/mL] and angiotensin 2 [median: 20.0(12.0-35.0) ng/L]. Multivariate adjusted ANCOVA showed a steady increase of PRC values across declining deciles of 25(OH)D and 1.25(OH)2D values (P=0.013 and P=0.045), respectively. Additionally, mean angiotensin 2 values increased significantly across decreasing 25(OH)D and 1,25(OH)2D values (P=0.020 and P=0.024, respectively). In contrast, multivariate adjusted ANCOVA revealed no significant associations between aldosterone, aldosterone-to-renin ratio and 25(OH)D/1,25(OH)2D values. In multivariate stepwise regression analyses both, 25(OH)D and 1,25(OH)2D emerged as independent predictors of plasma renin and angiotensin 2 concentrations. Conclusions: Our data showed for the first time in humans that both, lower 25(OH)D and 1,25(OH)2D values are independently related to an upregulated circulating RAS. (C) 2010 Elsevier B.V. All rights reserved.