Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study.
BACKGROUND
Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol+/-thiazide-based versus amlodipine+/-perindopril-based therapy) on derived central aortic pressures and hemodynamics.


RESULTS
The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Delta0.7 mm Hg; 95% CI, -0.4 to 1.7; P=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Delta4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, Delta3.0 mm Hg; 95% CI, 2.1 to 3.9; P<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc-defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P<0.0001; adjusted for baseline variables, P<0.05).


CONCLUSIONS
BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Bryan
B
Williams
Peter S
PS
Lacy
Simon M
SM
Thom
Kennedy
K
Cruickshank
Alice
A
Stanton
David
D
Collier
Alun D
AD
Hughes
H
H
Thurston
Michael
M
O'Rourke
D017677:Age Distribution; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000503:physiopathology*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use; D051437:Renal Insufficiency; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D049993:Sodium Chloride Symporter Inhibitors; D017311:Amlodipine; D001262:Atenolol; D020913:Perindopril