Losartan improves exercise tolerance in patients with diastolic dysfunction and hypertensive response to exercise

OBJECTIVES The aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and marked increase in systolic blood pressure (SBP) during exercise. BACKGROUND Diastolic dysfunction may be exacerbated during exercise, especially if there is marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance. METHODS We performed randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 ± 10 years with normal left ventricular systolic function (EF >50%), no ischemi on stress echocardiogram, mitral flow velocity E/ <1, normal resting SBP (<150 mm Hg), and hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesot Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by two-week washout period. RESULTS Resting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 ± 2.5 (mean ± SD) min, with peak exercise SBP of 226 ± 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 ± 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 ± 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 ± 2.0 min) or peak exercise SBP (217 ± 26 mm Hg). Quality of life improved with losartan (18 ± 22, p < 0.05) compared to placebo (22 ± 26). CONCLUSIONS In patients with Doppler evidence of diastolic dysfunction at rest and hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.