Activity of the Angiotensin-Converting Enzyme Mediates the Association Between Plasma Vitamin D and Plasma Aldosterone in Hypertensive Patients

Abstract

Objective: Deficiency of 25-OH Vitamin D (25OHD) and activation of the renin-angiotensin-aldosterone system (RAAS) are both known cardiovascular risk factors. Some studies have shown that 25OHD has a suppressive effect on RAAS but data in literature are conflicting. The aim of the study was to evaluate the relationships between 25OHD level and RAAS parameters in essential hypertensive (EH) patients without obesity and of severe impairment of renal function. Design and method: In 153 EH subjects (age 49 ± 12 years, 87 males, 123 naive, 30 after a wash-out period) we evaluated clinical characteristics, glomerular filtration rate (GFR), plasma levels of 25OHD, 1,25OHD, PTH, potassium, calcium, plasma aldosterone (PA), active renin (AR), angiotensin-converting-enzyme (ACE), 24-h urinary calcium (UCa) and 24-h urinary sodium. Results: 25OHD level was significantly and directly related with UCa (r = 0.209, P = 0.024), ACE (r = 0.470, P < 0.001), PA (r = 0.272, P = 0.001), and inversely related with age (r = -0.301, P < 0.001) and PTH level (r = -0.188, P = 0.025). At multivariate analysis, 25OHD level was independently associated with levels of PTH (B = -0.213, P = 0.023), ACE (B = 0.488, P < 0.001) and PA (B = 0.201, P = 0.039). PA level was positively related with 25OHD, 1,25-OHD (r = 0.256, P = 0.026), and ACE (r = 0.296, P = 0.006) and inversely related with age (r = -0.260, P = 0.019), plasma potassium (r = -0.261, P = 0.001) and alcohol intake (r = -0.224, P = 0.007). In a multivariate model that did not include ACE, PA was independently associated with levels of plasma potassium (B = -0.227, P = 0.004) and 25OHD (B = 0.197, P = 0.018). After inclusion of ACE, PA level remained independently associated only with plasma potassium (B = -0.244, P = 0.015) and alcohol intake (B = -0.244, P = 0.016). At multivariate analysis with ACE as the dependent variable and 25OHD and PA as independent variables, ACE was independently associated with 25OHD level (B = 0.427, P < 0.001). Conclusions: In patients with EH, PA and 25OHD are directly related and this relationship appears to be mediated by the activity of ACE.