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.
Little
William C
WC
Cardiology Section, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. wlittle@wfubmc.edu
Zile
Michael R
MR
Klein
Allan
A
Appleton
Christopher P
CP
Kitzman
Dalane W
DW
Wesley-Farrington
Deborah J
DJ
D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*
D000959:Antihypertensive Agents; D004232:Diuretics; D006852:Hydrochlorothiazide; D019808:Losartan