Effect of Losartan and Hydrochlorothiazide on Exercise Tolerance in Exertional Hypertension and Left Ventricular Diastolic Dysfunction

A randomized, double-blind study of 6 months of losartan 50 mg or hydrochlorothiazide (HCTZ) 12.5 mg was performed in 40 subjects with left ventricular diastolic dysfunction (mitral flow velocity E/A ratio <1), exercise systolic blood pressure (BP) >200 mm Hg, systolic BP at rest <150 mm Hg, ejection fraction >50%, and no ischemia. Before treatment, exercise systolic BP was 213 ± 13 mm Hg (mean ± SD) in the 19 patients randomized to losartan and 209 ± 11 mm Hg in the 21 patients who received HCTZ. After 6 months, exercise systolic BP was similarly reduced in patients who received losartan (197 ± 23 mm Hg, p <0.01) and HCTZ (191 ± 11 mm Hg, p <0.01). With losartan, treadmill exercise time increased from 894 ± 216 to 951 ± 225 seconds (p = 0.011), and quality of life improved from 15 ± 12 to 7 ± 10 (p = 0.015) without a change in oxygen consumption (1,895 ± 470 to 1,954 ± 539 ml/min, p = 0.30). With HCTZ, exercise time (842 ± 225 to 872 ± 239 seconds, p = 0.32) and quality of life (19 ± 21 vs 19 ± 24, p = 0.43) did not change, whereas oxygen consumption decreased from 2,144 ± 788 to 1,960 ± 706 ml/min (p = 0.022). In conclusion, in patients with diastolic dysfunction and hypertensive responses to exercise, 6 months of losartan and HCTZ blunted systolic BP during exercise. Only losartan increased exercise tolerance and improved quality of life.