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

The CAFE InvestigatorsFrom 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,Bryan WilliamsFrom 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,Peter LacyFrom 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,Simon ThomFrom 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,Kennedy CruickshankFrom 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,Alice StantonFrom 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,David CollierFrom 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,Alun D. HughesFrom 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,H. ThurstonFrom 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,Michael F. O’RourkeFrom 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,
2006en
ABI

Аннотация

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.

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