CLINICAL STUDIES
Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise
James G. Warner, Jr., MD, EdD, FACCa,
D. Christopher Metzger, MDa,
Dalane W. Kitzman, MD, FACCa,
Deborah J. Wesley, RN, BSNa and
William C. Little, MD, FACCa
a Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045, USA
Manuscript received August 20, 1998;
revised manuscript received December 8, 1998,
accepted January 21, 1999.
Reprint requests and correspondence: Dr. William C. Little, Cardiology Section, Wake Forest University School of Medicine, Bowman Gray Campus, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045
wlittle{at}wfubmc.edu
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.
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Abbreviations and Acronyms
| | 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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