title: Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction.
abstract: 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.
authors.affiliation: Cardiology Section, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157-1045, USA. wlittle@wfubmc.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Little
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Wesley-Farrington
authors.forename: John
authors.initials: J
authors.lastname: Hoyle
authors.forename: Steffen
authors.initials: S
authors.lastname: Brucks
authors.forename: Scott
authors.initials: S
authors.lastname: Robertson
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.forename: Che-Ping
authors.initials: CP
authors.lastname: Cheng
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018592:Cross-Over Studies; D003971:Diastole; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D013777:Tetrazoles / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D014700:Verapamil; C081643:candesartan