Benefits from angiotensin-converting enzyme inhibitor 'beyond blood pressure lowering': beyond blood pressure or beyond the brachial artery?
OBJECTIVE
The substantial benefits of ramipril over conventional therapy in high-risk patients are not always associated with clinically significant differences in brachial arterial pressure, and largely remain unexplained. We undertook this acute study to establish the magnitude of and reason for different acute effects of ramipril and atenolol on arterial pressure.


METHODS
We enrolled 30 patients, who took 10 mg ramipril, 100 mg atenolol, and placebo at intervals of > or = 7 days, in a randomized, double-blind, placebo-controlled trial. After baseline, measurements were taken at 30-60 min intervals for 5 h, and comprised cuff brachial pressure, radial artery tonometry with generation of central aortic pressure, and pulse wave velocity for aorta, upper limb and lower limb arteries.


RESULTS
Both ramipril and atenolol reduced arterial pressure, and the diastolic pressure fall was similar in the aorta and brachial artery, but the systolic pressure fall for ramipril was greater than for atenolol (by 5.2 mmHg, P < 0.0001) in the aorta compared with the brachial artery. The aortic systolic pressure difference with ramipril in comparison with atenolol was accompanied by an absolute difference of 10.7% (P < 0.0001) in the augmentation index, denoting a reduction in peripheral wave reflection by ramipril. The aortic pulse wave velocity fell to a similar degree with ramipril in comparison with atenolol, but fell to a greater degree (1.35 and 0.44 m/s, respectively, P < 0.0001 for both) in muscular arteries of the lower and upper limbs.


CONCLUSIONS
A greater (average, 5.2 mmHg) decrease in aortic systolic pressure caused by ramipril may explain the greater benefit of ramipril over atenolol. The difference is attributable to decreased stiffness of peripheral arteries and a reduction in wave reflection.
Hirata
Kozo
K
St Vincent's Hospital and Clinic, University of New South Wales, Darlinghurst NSW, Sydney, Australia.
Vlachopoulos
Charalambos
C
Adji
Audrey
A
O'Rourke
Michael F
MF
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001011:Aorta / Q000502:physiology; D001262:Atenolol / Q000008:administration & dosage; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011673:Pulsatile Flow / Q000187:drug effects; D017257:Ramipril / Q000008:administration & dosage*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010919:Placebos; D001262:Atenolol; D017257:Ramipril