Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study

Circulation. 2006 Mar 7;113(9):1213-25. doi: 10.1161/CIRCULATIONAHA.105.595496. Epub 2006 Feb 13.

Abstract

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.

Methods and 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Amlodipine / pharmacology
  • Amlodipine / therapeutic use
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Aorta / physiopathology*
  • Atenolol / pharmacology
  • Atenolol / therapeutic use
  • Blood Pressure / drug effects*
  • Brachial Artery / physiopathology
  • Cardiovascular Diseases
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Male
  • Middle Aged
  • Perindopril / pharmacology
  • Perindopril / therapeutic use
  • Renal Insufficiency
  • Sodium Chloride Symporter Inhibitors / pharmacology
  • Sodium Chloride Symporter Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Sodium Chloride Symporter Inhibitors
  • Amlodipine
  • Atenolol
  • Perindopril