Mineralocorticoid Receptor Blockade does not Reduce Pulse Wave Velocity in Older Adults with Metabolic Syndrome

Abstract

Arterial stiffness, an independent predictor of cardiovascular disease, is elevated in aging and metabolic syndrome (MS). We hypothesized that chronically elevated MR activation is partly responsible for increased arterial stiffness in aging/MS and that MR blockade would lead to greater decreases in arterial stiffness in middle-aged (MA) and older (O) adults with vs. without MS. PURPOSE: To examine the effect of 4-week MR blockade vs. placebo on arterial stiffness in MA/O adults with vs. without MS. METHODS: Using a randomized, double blind, crossover design, 100mg per day of Eplerenone (MR blocker) or placebo was administered orally for 4 weeks, with a 4-week washout, in 8 MA/O adults with (4 men & 4 women) vs. 15 (6 men & 9 women) without MS. Pulse wave velocity (PWV), a measure of arterial stiffness, was determined by positioning 2 Doppler flow meters at the suprasternal notch and femoral artery (aortic; AoPWV), femoral and posterior tibial artery (leg; LPWV), and brachial and radial artery (arm; ArPWV). RESULTS: MS risk factors expressed as an overall Z score were elevated in the MA/O adults with MS vs. without MS (0.7±0.2 vs. -0.4±0.1, P<0.0001) but age was similar between the 2 groups (63±3 vs. 64±1 years, P=0.7). Contrary to our hypothesis, PWV measures did not change in response to the MR blockade compared with placebo (AoPWV, 885±140 vs. 864±140 cm/sec, P=0.6; LPWV, 1364±48 vs. 1310±49 cm/sec, P=0.4; ArPWV, 1152±70 vs. 1153±±77 cm/sec, P=0.9) and the change in PWV was not different in the MA/O adults with vs. without MS (AoPWV, 816±241 vs. 934±139 cm/sec, P=0.8; LPWV, 1404±58 vs. 1270±39 cm/sec, P=0.7; ArPWV, 1140±102 vs. 1165±65 cm/sec, P=0.4). CONCLUSION: These results indicate that arterial stiffness in MA/O adults, independent of MS, is not modulated by MR blockade. Alternatively, the duration of the MR blockade may not be long enough to elicit changes in arterial stiffness as measured by PWV. Supported by AHA Grant 0865117F and NIH Grant AG032067.