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.

Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction.

Diastolic dysfunction may be exacerbated by increased systolic blood pressure (SBP) during exercise. Ang II may contribute to this process. We performed a randomized, double-blind, crossover study of two weeks of candesartan (16 mg) and verapamil (SR 160 mg). The 21 subjects were 64 +/- 10 years old with ejection fraction greater than 50%, no ischemia, mitral flow velocity E/A less than 1, normal resting SBP (< 150 mm Hg), and SBP greater than 200 mm Hg during exercise. Exercise tolerance was assessed using a Modified Bruce Protocol at baseline and after each two-week treatment period, separated by a two-week washout period. Quality of life (QOL) was assessed using the Minnesota Living with Heart Failure questionnaire. During exercise, Ang II levels increased from 29 +/- 18 to 33 +/- 18 pg/ml (P < 0.05). SBP during exercise was 213 +/- 9 mm Hg at baseline and similarly reduced by candesartan (198 +/- 18, P < 0.01) and verapamil (197 +/- 14, P < 0.01). With candesartan, exercise time increased from 793 +/- 182 seconds to 845 +/- 163 seconds (P < 0.05), and QOL improved from 11 +/- 14 to 5 +/- 6 (P < 0.05). In contrast, verapamil did not significantly improve exercise time or QOL. In patients with mild diastolic dysfunction at rest and a hypertensive response to exercise, both Ang II receptor blockade and verapamil blunted the hypertensive response to exercise. Ang II blockade increased exercise tolerance and improved QOL.