Impact of Spironolactone on Vascular, Myocardial, and Functional Parameters in Untreated Patients With a Hypertensive Response to Exercise

Abstract

Although a hypertensive response to exercise (HRE) is associated with cardiac risk and masked hypertension (MHT), its mechanisms and appropriate treatment remain unclear. We investigated spironolactone as a treatment for abnormal vascular and myocardial stiffness in HRE. In this randomized, double-blind, placebo-controlled study of 115 patients (54 ± 9 years, 57% men) with an HRE (≥210/105 mm Hg in men; ≥190/105 mm Hg in women) but no prior history of hypertension or myocardial ischemia, MHT prevalence was 40%. Patients were randomized to spironolactone 25mg daily (n = 58) or placebo (n = 57) and underwent evaluation at baseline and 3 months with exercise echocardiography, VO2max, pulse wave velocity (PWV), exercise and central blood pressure (BP), and 24-hour ambulatory BP. Changes in left ventricular mass index (LVMI), Doppler-derived E/em ratio (LV filling pressure), and myocardial strain were assessed. Baseline 24-hour systolic BP (SBP) was 133 ± 10 mm Hg and peak-exercise SBP was 219 ± 16 mm Hg. Peak systolic strain (0.3 ± 3.6% vs. -0.1 ± 3.2, P = 0.56), E/em (-1.1 ± 2.3 vs. -0.6 ± 1.7, P = 0.30), VO(2max) (0.4 ± 4.9 vs. -0.9 ± 4.1 ml/kg/min, P = 0.15), and adjusted PWV did not significantly change with treatment, despite reduction in exercise SBP, 24-hour SBP, and LVMI. The change in exercise E/em was of borderline significance (-0.3 ± 2.4 vs. 0.8 ± 2.8, P = 0.06) and became significant after adjustment for baseline differences (P = 0.01). Patients with higher LVMI significantly increased VO(2max) (1.1 ± 5.6 vs. -2.4 ± 4.4 ml/kg/min, P < 0.05) and reduced exercise E/e(m) (-0.7 ± 2.7 vs. 1.9 ± 2.8, P < 0.05). In HRE patients without previous hypertension, short-term spironolactone reduced exercise BP, 24-hour ambulatory BP, LVMI, and E/e(m) but did not significantly alter exercise capacity or myocardial strain.