Renal dysfunction enhances, and nifedipine retards coronary artery calcifications in high risk hypertensives: insights from an insight substudy

Abstract

Renal failure may be associated with adverse coronary outcome. We examined the progression of coronary atherosclerosis as measured by dual-section spiral computed tomography using total coronary artery calcium score (TCS) as a quantitative measure of the burden of atherosclerosis. In this side-arm of the INSIGHT study, 313 high risk Israeli hypertensive patients completed the prospective calcification study. Subjects were studied on placebo and after 3 years of treatment (nifedipine or thiazide/amiloride combination). Patients were divided to 2 groups depending on their creatinine clearance: ≤60 ml/min, average 51±1ml/min-renal dysfunction group(RD) (n=53), and, >60 ml/min -normal renal function (NRF) group, average 90±1ml/min (n=260). Baseline blood pressure (BP), cholesterol, smoking rate, and TCS did not differ and were 166±2/92±1mmHg, 235±12mmol/l, 17%, and 141±27 points in NRF, and 166±1/93±1mmHg, 214±11 mmol/l, 15%, and 183±37 points in RD respectively. Age 68±1 years, males 70%, diabetes mellitus (DM) 15%, ischemic heart disease (IHD) 30%, body mass index (BMI) 26.7±0.4 Kg/M2, and serum creatinine 123.2±4.4mmol/l in the RD group differed significantly, p<0.0001 from NRF group, 63±1years, males 48%, DM 31%, IHD 11%, BMI 29.5±0.3Kg/M2, and serum creatinine 79.2±0.88mmol/l. After 3 years of treatment BP control was similar: 140 ±2/79±1 mmHg in the RD vs.138±1/81±1 mmHg in the NRF group, whereas the TCS progression was 2 fold greater in the RD than the NRF group, 156±32 vs. 64±8 score points, respectively, p=0.006. In a multiple logistic regression analysis the odds ratio (OR) for TCS progression was highest for the RD group 2.1 with 95%confidence interval (CI) of 1.2-3.7, as well as for treatment with thiazide/amiloride combination, OR 1.66 95%CI 1.09-2.51. Gender, BMI, smoking, cholesterol, and DM were not significant predictors. Absence of IHD and younger age offered protection OR of 0.32 95%CI 0.17-.059 and 0.96 95%CI 0.93-0.99, respectively. In conclusion we found in a prospective randomized evaluation that even mild renal dysfunction accelerates coronary artery calcifications, above and beyond conventional risk factors,but less so in nifedipine as compared to diuretic treated subjects.