Background: We aimed to test the hypothesis that the angiotensin II receptor blocker (ARB)/diuretic combination decreases the urinary albumin/creatinine ratio (UACR) to a greater extent than treatment with the ARB/calcium-channel blocker (CCB) combination through a mechanism related to a greater reduction of sleep blood pressure (BP).
Methods: We conducted a prospective, randomized, open-label, blinded end-point trial in hypertensive patients. Patients received olmesartan monotherapy for 12 weeks, followed by an additional use of hydrochlorothiazide (HCTZ) (n = 104) or azelnidipine (n = 103) for 24 weeks after randomization. The measurements of central and ambulatory BP, and laboratory tests were performed at baseline and the end of the study.
Results: The adjusted percent reduction in UACR in the olmesartan/HCTZ group was significantly greater than that in the olmesartan/azelnidipine group (-43.2 vs. -24.0%, P = 0.0014), although the olmesartan/azelnidipine group showed greater decreases in central systolic BP (SBP; P = 0.04), oxidative stress (urinary 8-isoprostane; P = 0.02), inflammation (high-sensitivity C-reactive protein; P = 0.04), and insulin resistance (the homeostasis model assessment insulin resistance index (HOMA(IR)); P < 0.001) than the olmesartan/HCTZ group. In multivariate regression analyses, the significant determinants of change in UACR in the olmesartan/HCTZ group were changes in sleep SBP (P < 0.001), central SBP (P = 0.01), estimated glomerular filtration rate (eGFR) (P = 0.02), and HOMA(IR) (P = 0.03), and those in the olmesartan/azelnidipine group were changes in central SBP (P = 0.001) and urinary 8-isoprostane (P = 0.02).
Conclusions: These data showed that the ARB/diuretic combination decreased UACR significantly more than the ARB/CCB combination, and this decrease in UACR was associated with a greater magnitude reduction in sleep SBP.