Impact of spironolactone on vascular, myocardial, and functional parameters in untreated patients with a hypertensive response to exercise

BACKGROUND 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. METHODS In this randomized, double-blind, placebo-controlled study of 115 patients (54¡À9 years, 57% men) with an HRE (¡Ý210/105mm Hg in men; ¡Ý190/105mm 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. RESULTS Baseline 24-hour systolic BP (SBP) was 133¡À10mm Hg and peak-exercise SBP was 219¡À16mm Hg. Peak systolic strain (0.3¡À3.6% vs. -0.1¡À3.2, P = 0.56), E/em (-1.1¡À2.3 vs. -0.6¡À1.7, P = 0.30), VO2max (0.4¡À4.9 vs. -0.9¡À4.1ml/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¡À2.4 vs. 0.8¡À2.8, P = 0.06) and became significant after adjustment for baseline differences (P = 0.01). Patients with higher LVMI significantly increased VO2max (1.1¡À5.6 vs. -2.4¡À4.4ml/kg/min, P < 0.05) and reduced exercise E/em (-0.7¡À2.7 vs. 1.9¡À2.8, P < 0.05). CONCLUSIONS In HRE patients without previous hypertension, short-term spironolactone reduced exercise BP, 24-hour ambulatory BP, LVMI, and E/em but did not significantly alter exercise capacity or myocardial strain.