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

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Abstract

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 a marked increase in systolic blood pressure (SBP) during exercise.

BACKGROUND

Diastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance.

METHODS

We performed a 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 ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a 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 a 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 a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.

Abbreviations

ACE
angiotensin-converting enzyme
Ang II
angiotensin II
BP
blood pressure
IVRT
isovolumetric relaxation time
LV
left ventricular
SBP
systolic blood pressure

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This work was supported in part by research grants from the NIH (AG12257) and from Merck Research Laboratories.