title: Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiology Section, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1045, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Warner
authors.forename: D C
authors.initials: DC
authors.lastname: Metzger
authors.forename: D W
authors.initials: DW
authors.lastname: Kitzman
authors.forename: D J
authors.initials: DJ
authors.lastname: Wesley
authors.forename: W C
authors.initials: WC
authors.lastname: Little
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005080:Exercise Test / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D019808:Losartan