title: Excess pressure integral predicts cardiovascular events independent of other risk factors in the conduit artery functional evaluation substudy of Anglo-Scandinavian Cardiac Outcomes Trial.
abstract: Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial.
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Justin E
authors.initials: JE
authors.lastname: Davies
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Peter
authors.initials: P
authors.lastname: Lacy
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Therese
authors.initials: T
authors.lastname: Tillin
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: David
authors.initials: D
authors.lastname: Collier
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: J Kennedy
authors.initials: JK
authors.lastname: Cruickshank
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Anura
authors.initials: A
authors.lastname: Malaweera
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Alice
authors.initials: A
authors.lastname: Stanton
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Kim H
authors.initials: KH
authors.lastname: Parker
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.).
authors.forename: Simon A
authors.initials: SA
authors.lastname: McG Thom
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College Healthcare NHS Trust (J.E.D., D.P.F., A.M., J.M., S.A.M.T.) and Department of Bioengineering (K.H.P.), Imperial College London, London, United Kingdom; Institute of Cardiovascular Science and National Institute for Health Research (NIHR), University College London Hospitals Biomedical Research Centre, University College London, London, United Kingdom (P.L., T.T., B.W., A.D.H.); Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom (D.C.); Cardiovascular Medicine and Nutrition at King's College London, London, United Kingdom (J.K.C.); and Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland (A.S.). alun.hughes@ucl.ac.uk.
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D002319:Cardiovascular System / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents
keywords: blood pressure; cardiovascular diseases; carotid intima thickness; hypertension; left ventricular hypertrophy; pulse wave analysis