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(Circulation. 2006;113:1213-1225.)
© 2006 American Heart Association, Inc.

Hypertension

Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes

Principal Results of the Conduit Artery Function Evaluation (CAFE) Study

The CAFE Investigators, for the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Investigators; CAFE Steering Committee and Writing Committee; Bryan Williams, MD, FRCP; Peter S. Lacy, PhD; Simon M. Thom, MD, FRCP; Kennedy Cruickshank, MD; Alice Stanton, MB, PhD, FRCPI; David Collier, MBBS, PhD; Alun D. Hughes, MBBS, PhD; H. Thurston, MD, FRCP; Study Advisor Michael O’Rourke, MD, FRACP

From the University Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (B.W., P.S.L., H.T.); National Heart & Lung Institute, International Center for Circulatory Health at St Mary’s Hospital, Imperial College London W2 ILA, London, UK (S.M.T., A.D.H.); Clinical Epidemiology Group, University Department of Medicine, Manchester Royal Infirmary, Manchester, UK (K.C.); Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen’s Green, Dublin, Ireland (A.S.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart’s & The London, Queen Mary’s School of Medicine & Dentistry, London, UK (D.C.); and University of New South Wales, Sydney, Australia (M.O.).

Reprint requests to Peter S. Lacy, PhD, Research Fellow, Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester, LE2 7LX, UK. E-mail psl2{at}le.ac.uk

Received October 14, 2005; revision received December 14, 2005; accepted December 16, 2005.

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 (0.7 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, 4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, 3.0 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.

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				P. Ou, D. S. Celermajer, O. Raisky, O. Jolivet, F. Buyens, A. Herment, D. Sidi, D. Bonnet, and E. Mousseaux Angular (Gothic) aortic arch leads to enhanced systolic wave reflection, central aortic stiffness, and increased left ventricular mass late after aortic coarctation repair: Evaluation with magnetic resonance flow mapping J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 62 - 68. [Abstract] [Full Text] [PDF]

				R. A. Payne and D. J. Webb Peripheral Augmentation Index: Shouldering the Central Pressure Load Hypertension, January 1, 2008; 51(1): 37 - 38. [Full Text] [PDF]

				R. S. Vasan Pathogenesis of Elevated Peripheral Pulse Pressure: Some Reflections and Thinking Forward Hypertension, January 1, 2008; 51(1): 33 - 36. [Full Text] [PDF]

				S. Munir, A. Guilcher, T. Kamalesh, B. Clapp, S. Redwood, M. Marber, and P. Chowienczyk Peripheral Augmentation Index Defines the Relationship Between Central and Peripheral Pulse Pressure Hypertension, January 1, 2008; 51(1): 112 - 118. [Abstract] [Full Text] [PDF]

				K. O. Stumpe, E. Agabiti-Rosei, T. Zielinski, D. Schremmer, J. Scholze, P. Laeis, P. Schwandt, and M. Ludwig Original Research: Carotid intima-media thickness and plaque volume changes following 2-year angiotensin II-receptor blockade. The Multicentre Olmesartan atherosclerosis Regression Evaluation (MORE) study Therapeutic Advances in Cardiovascular Disease, December 1, 2007; 1(2): 97 - 106. [Abstract] [PDF]

				C. M. Ferrario, J. Basile, W. Bestermann, E. Frohlich, M. Houston, D. T. Lackland, R. D. Smith, and D. L. Wise Review: The role of noninvasive hemodynamic monitoring in the evaluation and treatment of hypertension Therapeutic Advances in Cardiovascular Disease, December 1, 2007; 1(2): 113 - 118. [Abstract] [PDF]

				M. F. O'Rourke Arterial aging: pathophysiological principles Vascular Medicine, November 1, 2007; 12(4): 329 - 341. [Abstract] [PDF]

				J.-G. Wang and Y. Li Response to Amlodipine and Stroke Prevention Hypertension, October 1, 2007; 50(4): e72 - e72. [Full Text] [PDF]

				A. Benjo, R. E. Thompson, D. Fine, C. W. Hogue, D. Alejo, A. Kaw, G. Gerstenblith, A. Shah, D. E. Berkowitz, and D. Nyhan Pulse Pressure Is an Age-Independent Predictor of Stroke Development After Cardiac Surgery Hypertension, October 1, 2007; 50(4): 630 - 635. [Abstract] [Full Text] [PDF]

				M. Naya, T. Tsukamoto, K. Morita, C. Katoh, T. Furumoto, S. Fujii, N. Tamaki, and H. Tsutsui Olmesartan, But Not Amlodipine, Improves Endothelium-Dependent Coronary Dilation in Hypertensive Patients J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1144 - 1149. [Abstract] [Full Text] [PDF]

				K. Fox Contribution of perindopril to cardiology: 20 years of success Eur. Heart J. Suppl., September 1, 2007; 9(suppl_E): E10 - E19. [Abstract] [Full Text] [PDF]

				M. J Brown Renin: friend or foe? Heart, September 1, 2007; 93(9): 1026 - 1033. [Abstract] [Full Text] [PDF]