1600 John F.Kennedy Blvd. Suite 1800 Philadelphia,PA 19103-2899 HYPERTENSION:A COMPANION TO BRAUNWALD’S ISBN-13:978-1-4160-3053-9 HEART DISEASE ISBN-10:1-4160-3053-0 Copyright © 2007 by Saunders,an imprint ofElsevier Inc. All rights reserved.No part ofthis publication may be reproduced or transmitted in any form or by any means, electronic or mechanical,including photocopying,recording,or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia,PA, USA:phone:(+1) 215 239 3804,fax:(+1) 215 239 3805,e-mail:[email protected] may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com),by selecting ‘Customer Support’and then ‘Obtaining Permissions.’ Notice Knowledge and best practice in this field are constantly changing.As new research and experience broaden our knowledge,changes in practice,treatment,and drug therapy may become necessary or appropriate.Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer ofeach product to be administered to verify the recommended dose or formula,the method and duration ofadministration,and contraindications.It is the responsibility of practitioners,relying on their own experience and knowledge ofthe patient,to make diagnoses,to determine dosages and the best treatment for each individual patient,and to take all appropriate safety precautions.To the fullest extent ofthe law,neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out ofor related to any use ofthe material contained in this book. Library ofCongress Cataloging-in-Publication Data Black,Henry R.(Henry Richard) Hypertension :a companion to Braunwald’s heart disease / Henry R.Black, William J.Elliott.— 1st ed. p.;cm. Companion v.to:Braunwald’s heart disease / [edited by] Douglas P.Zipes ..[et al.].7th ed.c2005. Includes index. ISBN 1-4160-3053-0 1.Hypertension.2.Heart—Diseases.I.Elliott,William J.,M.D.II.Braunwald’s heart disease.III.Title. [DNLM:1.Hypertension.WG 340 B627c 2007] RC685.H8B553 2007 616.1’2—dc22 2006045231 Executive Publisher:Natasha Andjelkovic Developmental Editor:Jerisha Parker Publishing Services Manager:Frank Polizzano Project Manager:Lee Ann Draud Design Direction:Steve Stave Printed in Canada Last digit is the print number: 9 8 7 6 5 4 3 2 1 Henry R.Black To my wife,Benita,the love of my life and my perfect partner,and to Dana,Matt,and Sabrina, who make it all worthwhile.To our colleagues whose work is discussed in this volume and whose contributions to understanding and treating hypertension have saved millions of lives. William J.Elliott To my teachers (including my parents and spouse,Melicien Tettambel,DO),my family members,and my students,although it is still unclear from whom I learned (and continue to learn) more. vii Contributors Matthew A.Allison,MD,MPH Henry R.Black,MD Assistant Professor ofFamily and Preventive Medicine, Charles J.and Margaret Roberts Professor ofPreventive University ofCalifornia,San Diego,School ofMedicine, Medicine and Professor ofInternal Medicine,Rush Medical La Jolla,California College ofRush University at Rush University Medical Peripheral Arterial Disease in Hypertension Center,Chicago,Illinois Angiotensin Receptor Blockers Craig Anderson,MBBS,PhD,FRACP Professor ofStroke Medicine and Clinical Neuroscience, Michael J.Bloch,MD University ofSydney Faculty ofMedicine and the Institute of Associate Professor ofMedicine,University ofNevada School Neurosciences ofRoyal Prince Alfred Hospital;Director, ofMedicine;Medical Director,St.Mary’s Risk Reduction Neurological and Mental Health Division,The George Institute Center,Reno,Nevada for International Health,Sydney,Australia Hypertension in the Elderly Cerebrovascular Disease in Hypertension Emmanuel L.Bravo,MD Lawrence J.Appel,MD,MPH Consultant,Cleveland Clinic,Cleveland,Ohio Professor ofMedicine,Johns Hopkins University School of Secondary Hypertension: Mineralocorticoid Excess States Medicine,Baltimore,Maryland Diet and Blood Pressure Robert D.Brook,MD Assistant Professor,Department ofInternal Medicine, Phyllis August,MD,MPH University ofMichigan Medical School,Ann Arbor, Professor ofMedicine,Medicine in Obstetrics and Gynecology, Michigan and Public Health,and Program Director,Nephrology and Hypertension and the Perioperative Period Hypertension,Weill Medical College ofCornell University; New York–Presbyterian Hospital,New York,New York David A.Calhoun,MD Hypertension in Pregnancy Associate Professor ofMedicine,University ofAlabama Birmingham School ofMedicine,Birmingham, George L.Bakris,MD Alabama Professor ofInternal Medicine and Director ofthe Pathophysiology ofHypertension Hypertension Clinic in the Diabetes Institute,Pritzker School ofMedicine,University ofChicago,Chicago,Illinois Barry L.Carter,PharmD Kidney Disease in Hypertension Professor,College ofPharmacy and Department ofFamily Medicine,University ofIowa Roy J.and Lucille A.Carver Robert L.Bard,MA College ofMedicine,Iowa City,Iowa Research Associate,Endothelial Function Laboratory, Hypertension Disease Management Services University ofMichigan Medical Center,Ann Arbor,Michigan Hypertension and the Perioperative Period John Chalmers,MD,PhD,FRACP Emeritus Professor ofMedicine,University ofSydney Faculty Jan N.Basile,MD ofMedicine and Flinders University School ofMedicine; Professor ofMedicine,Medical University ofSouth Carolina; Honorary Consultant Physician,Royal Prince Alfred Hospital Lead Physician,Primary Care Service Line,Ralph H.Johnson and Sydney South West Area Health Service;Chairman ofthe Veterans Affairs Medical Center,Charleston,South Carolina Board ofDirectors and Senior Director and Head ofResearch Hypertension in the Elderly; Hypertensive Emergencies and Advisory Unit,The George Institute for International Health, Urgencies Sydney,Australia Cerebrovascular Disease in Hypertension Grzegorz Bilo,MD,PhD Research Assistant,Department ofClinical Medicine and Shalini Chandra,MD Prevention,University ofMilano-Bicocca,Milan,Italy;I Department ofInternal Medicine,Wayne State University Cardiac Department,Jagiellonian University,Krakow,Poland School ofMedicine,Detroit,Michigan Secondary Hypertension: Sleep Apnea Hypertension in African Americans viii Contributors Neil Chapman,BSc,MB BChir Larry E.Fields,MD,MBA,FACP Honorary Senior Lecturer,International Centre for Circulatory Director,Clinical Product Development,Medco Health Health,Imperial College;Consultant,Cardiovascular Solutions,Inc.,Franklin Lakes,New Jersey Physician,St.Mary’s Hospital,London,England U.S.and Canadian Guidelines for Hypertension Cerebrovascular Disease in Hypertension John M.Flack,MD,MPH,FAHA Kenneth L.Choi,MD Professor and Associate Chair for Academic Affairs,Internal Division ofNephrology and Hypertension,Department of Medicine Administration;Director ofCardiovascular Internal Medicine,University ofMiami School ofMedicine, Epidemiology and Clinical Applications (CECA) Program, Miami,Florida Wayne State University School ofMedicine,Detroit, Kidney Disease in Hypertension Michigan Hypertension in African Americans Richard S.Cooper,MD Professor and Chair,Department ofPreventive Medicine and Veronica Franco,MD,MSPH Epidemiology,Loyola University Chicago Stritch School of Instructor ofMedicine,Division ofCardiovascular Disease, Medicine,Chicago,Illinois University ofAlabama Birmingham School ofMedicine, Genetics ofHypertension Birmingham,Alabama Pathophysiology ofHypertension Michael H.Criqui,MD,MPH Professor ofMedicine and Vice Chair ofFamily and Stanley S.Franklin,MD,FACP,FACC,FASN Preventive Medicine,University ofCalifornia,San Diego, Clinical Professor ofMedicine and Associate Medical School ofMedicine,La Jolla,California Director ofthe UCI Heart Disease Prevention Program, Peripheral Arterial Disease in Hypertension University ofCalifornia,Irvine,School ofMedicine,Irvine, California Errol D.Crook,MD The Special Problem ofIsolated Systolic Hypertension Professor and Chairman,Department ofInternal Medicine, Division ofNephrology,University ofSouth Alabama Ronald S.Freudenberger,MD College ofMedicine,Mobile,Alabama Associate Professor ofMedicine,University ofMedicine & Hypertension in African Americans Dentistry ofNew Jersey—Robert Wood Johnson Medical School;Director,Heart Failure and Transplant Cardiology, Prakash C.Deedwania,MD,FACC,FACP,FAHA Robert Wood Johnson University Hospital,New Brunswick, Professor ofMedicine,University ofCalifornia,San New Jersey Francisco,School ofMedicine,San Francisco;Chief, Heart Failure in Hypertension Cardiology Section,Veterans Affairs Central California Health Care System,Fresno,California William H.Frishman,MD Hypertension in South Asians Rosenthal Professor and Chairman ofMedicine,New York Medical College;Director ofMedicine,Westchester Medical Mehul G.Desai,MD Center,Valhalla,New York Medical Officer,Division ofCardiovascular and Renal (cid:3)-Blockers in Hypertension Products,Center for Drug Evaluation and Research,Food and Drug Administration,Silver Spring,Maryland Philip B.Gorelick,MD,MHP,FACP Antihypertensive Drug Development: A Regulatory Perspective John S.Gavin Professor and Head,Department ofNeurology and Rehabilitation,University ofIllinois College ofMedicine Kim A.Eagle,MD,FACC at Chicago;Chief,Neurology Service,University ofIllinois at Albion Walter Hewlett Professor ofInternal Medicine, Chicago Medical Center,Chicago,Illinois University ofMichigan Medical School;Clinical Director, Assessment ofHypertensive Target Organ Damage University ofMichigan Cardiovascular Center,Ann Arbor, Michigan Guido Grassi,MD Hypertension and the Perioperative Period Professor ofMedicine,University ofMilano-Bicocca,Milan; Ospedale San Gerardo,Monza,Italy William J.Elliott,MD,PhD European,American,and British Guidelines: Similarities and Professor ofPreventive Medicine,Internal Medicine,and Differences Pharmacology,Rush Medical College ofRush University at Rush University Medical Center,Chicago,Illinois Carlene M.Grim,MSN,SpDN Secondary Hypertension: Renovascular Hypertension; The President,Shared Care Research and Education Consulting, Natural History ofUntreated Hypertension; Angiotensin Inc.,Milwaukee,Wisconsin Receptor Blockers; (cid:2)-Blockers Office Blood Pressure Measurement Bonita Falkner,MD Clarence E.Grim,MD,MS Professor ofMedicine and Pediatrics,Thomas Jefferson Clinical Professor ofMedicine and Professor ofEpidemiology, University,Philadelphia,Pennsylvania Medical College ofWisconsin,Milwaukee,Wisconsin Hypertension in Children and Adolescents Office Blood Pressure Measurement Contributors ix Ehud Grossman,MD Philip R.Liebson,MD,FACC,FAHA Vice Dean ofthe Faculty ofMedicine,Sackler School of McMullan-Eybel Chair ofExcellence in Clinical Cardiology, Medicine,Tel-Aviv University,Tel-Aviv;Head ofInternal Professor ofInternal Medicine,and Professor ofPreventive Medicine and Hypertension,Chaim Sheba Medical Center, Medicine,Rush Medical College ofRush University;Senior Tel-Hashomer,Israel Attending Physician,Rush University Medical Center, Rare and Unusual Forms ofHypertension Chicago,Illinois Assessment ofHypertensive Target Organ Damage Rajeev Gupta,MD Professor ofMedicine,Mahatma Gandhi National Institute Donald M.Lloyd-Jones,MD,ScM ofMedical Sciences;Consultant Physician,Marilek Hospital Assistant Professor ofPreventive Medicine and Assistant and Research Center,Jaipur,India Professor ofMedicine (Cardiology),Northwestern University Hypertension in South Asians Feinberg School ofMedicine;Associate in Medicine, Northwestern Medical Faculty Foundation,Northwestern David J.Hyman,MD,MPH Memorial Hospital,Chicago,Illinois Professor ofMedicine and Family and Community Epidemiology ofHypertension Medicine,Baylor College ofMedicine;Chief,General Internal Medicine,Ben Taub General Hospital,Houston, Carolina Lombardi,MD,PhD Texas Assistant Professor,University ofMilano-Bicocca;Head of Hypertension in Hispanics Sleep Medicine Unit,San Luca Hospital,Milan,Italy Secondary Hypertension: Sleep Apnea Joseph L.Izzo,Jr.,MD Professor ofMedicine,Pharmacology,and Toxicology,State Giuseppe Mancia,MD University ofNew York at Buffalo School ofMedicine and Professor ofMedicine,University ofMilano-Bicocca,Milan; Biomedical Sciences;Vice Chair,Department ofMedicine, Head ofInternal Medicine Division,Ospedale San Gerardo, Erie County Medical Center,Buffalo,New York Monza,Italy Assessment ofHypertensive Target Organ Damage Secondary Hypertension: Sleep Apnea; European,American, and British Guidelines: Similarities and Differences Panagiotis Kokkoris,MD Endocrinologist,Department ofEndocrinology,Diabetes,and Franz H.Messerli,MD Metabolism,Hellenic Air Force General Hospital,Athens,Greece Director,Hypertension Program,St.Luke’s-Roosevelt Obesity in Hypertension Hospital Center,New York,New York Rare and Unusual Forms ofHypertension John B.Kostis,MD John G.Detwiler Professor ofCardiology,Professor of Albert Mimram,MD Medicine and Pharmacology,and Chairman,Department of Professor and Head,Medicine and Hypertension Service, Medicine,University ofMedicine & Dentistry ofNew University ofMontpelier;Medicine and Hypertension Jersey—Robert Wood Johnson Medical School;Chiefof Service,Hôpital Lapeyronie,Montpelier,France Medical Service,Robert Wood Johnson University Hospital, Assessment ofHypertensive Target Organ Damage New Brunswick,New Jersey Heart Failure in Hypertension Marvin Moser,MD,FACP Clinical Professor ofMedicine,Yale University School of Jane Morley Kotchen,MD,MPH Medicine,New Haven,Connecticut Professor ofEpidemiology,Medical College ofWisconsin, Diuretic Therapy in Cardiovascular Disease Milwaukee,Wisconsin Defining Hypertension Maryann N.Mugo,MD Department ofInternal Medicine,University of Theodore A.Kotchen,MD Missouri–Columbia School ofMedicine,Columbia, Professor ofMedicine and Epidemiology and Associate Dean Missouri for Clinical Research,Medical College ofWisconsin, Hypertension and Diabetes Mellitus Milwaukee,Wisconsin Defining Hypertension Samar A.Nasser,PAC,MPH Department ofInternal Medicine,Wayne State University John C.LaRosa,MD School ofMedicine,Detroit Michigan President and Professor ofMedicine,State University ofNew Hypertension in African Americans York Downstate Medical Center,Brooklyn,New York Dyslipidemia in Hypertension Bruce Neal,MB ChB,PhD,MRCP Associate Professor ofMedicine,University ofSydney Daniel Levy,MD Faculty ofMedicine;Senior Director,Research and Professor,Boston University School ofMedicine,Boston; Development,The George Institute for International Health; Director,National Heart,Lung,and Blood Institute’s Honorary Consultant Epidemiologist,Royal Prince Alfred Framingham Heart Study,Framingham,Massachusetts Hospital,Sydney,Australia Epidemiology ofHypertension Meta-analyses ofHypertension Trials x Contributors James D.Neaton,PhD Priya G.Rao,DO Professor ofBiostatistics,School ofPublic Health,University Department ofInternal Medicine,University of ofMinnesota,Minneapolis,Minnesota Missouri–Columbia School ofMedicine,Columbia,Missouri Design ofOutcome Studies Hypertension and Diabetes Mellitus Suzanne Oparil,MD Shakaib U.Rehman,MD Professor ofMedicine and Physiology and Biophysics, Associate Professor ofMedicine,Medical University ofSouth University ofAlabama Birmingham,School ofMedicine; Carolina;Physician Manager,Primary Care,Ralph H.Johnson Senior Scientist,Center for Aging,and Director,Vascular Veterans Affairs Medical Center,Charleston,South Carolina Biology and Hypertension Program,University ofAlabama Hypertensive Emergencies and Urgencies Birmingham,Birmingham,Alabama Pathophysiology ofHypertension James J.Reidy,MD Professor ofOphthalmology and Director ofthe Cornea Gianfranco Parati,MD Service,State University ofNew York at Buffalo School of Professor ofMedicine,Department ofClinical Medicine and Medicine and Biomedical Sciences;Clinical Director, Prevention,University ofMilano-Bicocca;Head,II Department ofOphthalmology,Erie County Medical Center, Cardiology Unit,San Luca Hospital,Milan,Italy Buffalo,New York Secondary Hypertension: Sleep Apnea Assessment ofHypertensive Target Organ Damage Valory N.Pavlik,PhD Clive Rosendorff,MD,PhD,DScMed Associate Professor,Department ofFamily and Community Professor ofMedicine,Mount Sinai School ofMedicine,New Medicine,Baylor College ofMedicine,Houston,Texas York;Physician,James J.Peters Veterans Affairs Medical Hypertension in Hispanics Center,Bronx,New York Ischemic Heart Disease in Hypertension Thomas G.Pickering,MD,DPhil Professor ofMedicine,Columbia University College of John F.Setaro,MD Physicians and Surgeons;Director,Behavioral Associate Professor ofMedicine,Section on Cardiovascular Cardiovascular Health and Hypertension Program, Medicine,Yale University School ofMedicine,New Haven, Columbia Presbyterian Medical Center,New York, Connecticut New York Resistant Hypertension Home Monitoring ofBlood Pressure Tariq Shafi,MD Paul Pisarik,MD,MPH Assistant Professor,Clinical Internal Medicine,Wayne State Assistant Professor,Department ofFamily Medicine,University University School ofMedicine,Detroit,Michigan ofOklahoma College ofMedicine,Tulsa,Oklahoma Hypertension in African Americans Hypertension in Hispanics Alexander M.M.Shepherd,MD,PhD F.Xavier Pi-Sunyer,MD,MPH Professor and Chief,Division ofClinical Pharmacology, Professor ofMedicine,Columbia University College of University ofTexas Health Science Center at San Antonio, Physicians and Surgeons;Chief,Division ofEndocrinology, San Antonio,Texas Diabetes,and Nutrition,St.Luke’s–Roosevelt Hospital,New New and Investigational Drugs for Hypertension York,New York Obesity in Hypertension Domenic A.Sica,MD Professor ofMedicine,Medical College ofVirginia at Virginia Tiina Podymow,MD Commonwealth University;Chairman,Section ofClinical Associate Professor,McGill University Faculty ofMedicine; Pharmacology and Hypertension,Virginia Commonwealth Division ofNephrology,Royal Victoria Hospital,Montreal, University Health Systems,Richmond,Virginia Quebec,Canada Diuretic Therapy in Cardiovascular Disease; Angiotensin- Hypertension in Pregnancy Converting Enzyme Inhibitors James L.Pool,MD James R.Sowers,MD,FACE,FACP,FAHA Professor ofMedicine and Pharmacology and the James L. Associate Dean for Clinical Research and Professor of Pool Endowed Chair in Clinical Pharmacology,Baylor Internal Medicine,Physiology,and Pharmacology,University College ofMedicine;Director,Hypertension-Clinical ofMissouri–Columbia School ofMedicine,Columbia, Pharmacology Research Clinic,Department ofMedicine, Missouri Baylor College ofMedicine,Houston,Texas Hypertension and Diabetes Mellitus (cid:2)-Blockers Norman Stockbridge,MD,PhD Jason Ramos,MD Director,Division ofCardiovascular and Renal Products, Department ofInternal Medicine,Wayne State University Center for Drug Evaluation and Research,Food and Drug School ofMedicine,Detroit,Michigan Administration,Silver Spring,Maryland Hypertension in African Americans Antihypertensive Drug Development: A Regulatory Perspective Contributors xi Craig S.Stump,MD,PhD William B.White,MD Assistant Professor ofMedicine,Division ofEndocrinology, Professor ofMedicine,University ofConnecticut School of University ofMissouri–Columbia School ofMedicine; Medicine;Chief,Division ofHypertension and Clinical Research Scientist,Harry S Truman Memorial Veterans Pharmacology,Calhoun Cardiology Center,and Medical Hospital,Columbia,Missouri Director,Clinical Trials Unit,University ofConnecticut Hypertension and Diabetes Mellitus Health Center,Farmington,Connecticut Ambulatory Blood Pressure Monitoring in Hypertension Sandra J.Taler,MD Associate Professor ofMedicine,Mayo Medical School; Peter W.F.Wilson,MD Consultant,Department ofInternal Medicine,Division of Professor ofMedicine,Department ofEndocrinology, Nephrology and Hypertension,Mayo Clinic College of Diabetes,and Medical Genetics,Medical University ofSouth Medicine,Rochester,Minnesota Carolina;Program Director,General Clinical Research Transplant Hypertension Center,Charleston,South Carolina Prediction ofGlobal Cardiovascular Risk in Hypertension Robert Temple,MD Associate Director for Medical Policy,Center for Drug Nathan D.Wong,PhD,MPH Evaluation and Research,Food and Drug Administration, Professor and Director,Heart Disease Prevention Program, Silver Spring,Maryland University ofCalifornia,Irvine,School ofMedicine,Irvine, Antihypertensive Drug Development: A Regulatory Perspective California Hypertension in East Asians and Pacific Islanders Douglas C.Throckmorton,MD Deputy Center Director,Center for Drug Evaluation and Xiaodong Wu,PhD Research,Food and Drug Administration,Silver Spring, Assistant Professor,Department ofPreventive Medicine and Maryland Epidemiology,Loyola University Chicago Stritch School of Antihypertensive Drug Development: A Regulatory Perspective Medicine,Chicago,Illinois Genetics ofHypertension Fiona Turnbull,MB ChB,FAFPHM Senior Research Fellow,The George Institute for William F.Young,Jr.,MD,MSc International Health;Sydney,Australia Professor ofMedicine,Mayo Clinic College ofMedicine; Meta-analyses ofHypertension Trials Vice-Chair,Division ofEndocrinology,Diabetes, Metabolism,and Nutrition,Mayo Clinic,Rochester, Carlos Vallbona,MD Minnesota Distinguished Service Professor,Department ofFamily and Secondary Hypertension: Pheochromocytoma Community Medicine,Baylor College ofMedicine;Chiefof Staff,Community Health Program,Harris County Hospital Alberto Zanchetti,MD District,Houston,Texas Emeritus Professor ofInternal Medicine,University of Hypertension in Hispanics Milan;Scientific Director,Instituto Auxologico Italiano, Milan,Italy Donald G.Vidt,MD Calcium Channel Blockers in Hypertension Consultant,Department ofHypertension and Nephrology, Cleveland Clinic Foundation,Cleveland,Ohio Hypertensive Emergencies and Urgencies xiii Foreword Hypertension has been recognized as an important cardiovas- enormous amount has been learned about the mechanisms of cular disorder since the dawn ofthe 20th century,when Riva- action and efficacy of the numerous classes of antihyperten- Rocci and then Korotkoffdescribed the sphygmomanometric sive agents. For the first time, rigorous comparisons among method of measuring arterial pressure. Although hyperten- these classes have been conducted.Revised practice guidelines sion has been studied intensively since then,this is an extraor- that synthesize much useful information for clinical practice dinary time for investigators, teachers, and clinicians in the have become available. field.It is a time when hypertension is spreading to the devel- The goal of the Companions to Heart Disease: A Textbook oping world and is reaching pandemic proportions. More of Cardiovascular Medicine is to provide cardiologists and inclusive definitions as well as more accurate and detailed trainees in this field with important additional information in measurements of blood pressure indicate that the prevalence critically important segments of cardiology that go beyond of hypertension is even greater in the United States and what is contained in the “mother book,”thereby creating an Europe than had previously been thought. Also, the health extensive cardiovascular information system. Hypertension, threat of hypertension in the pathogenesis of coronary heart brilliantly edited by Drs.Henry R.Black and William J.Elliott disease,heart failure,cerebrovascular disease,peripheral vas- and superbly written by distinguished leaders in the field, cular disease, and renal failure probably exceeds what we clearly accomplishes this goal. We are delighted to welcome appreciated in the past. this companion into the “family.” At the same time,this is a time of unprecedented oppor- Eugene Braunwald tunity to deal effectively with this serious health problem. Douglas P.Zipes Research carried out in the last 5 years is unraveling the patho- Peter Libby genesis and genetics of hypertension. Simultaneously, an Robert O.Bonow xv Preface Hypertension is one of the most important public health Chronic kidney disease,an independent risk factor for cardio- problems worldwide, and its impact is expected to increase vascular disease, too often results in end-stage renal disease over the next 20 years as economically developing nations (dialysis or kidney transplantation), which has the highest improve sanitation, infant mortality, and childhood immu- annualized per-patient cost ofany program supported by the nization rates (among other measures).1 The prevalence of Centers for Medicare and Medicaid Services. Although dia- hypertension in adults is expected to grow from 26.4% betes has typically ranked first among sole “causes”ofdialysis (in 2000) to 29.2% in 2025, with most of the growth from for about 20 years,hypertension has ranked second for about 972 million to the projected 1.56 billion affected people the same period oftime,and,when more than one cause was occurring outside ofNorth America and Europe.1This global allowed to be cited,hypertension was either the primary or a “epidemic” of high blood pressure is expected to shift the secondary cause of end-stage renal disease in 72% of those burden of disease so that heart disease will become the most who began dialysis in 2003.10Hypertension ranks second (to common cause ofdeath worldwide by the year 2025.2 diabetes) as a cause of peripheral vascular disease, the most In the United States, hypertension is the most important common cause oflower limb amputations in 2003.4Although and most ubiquitous risk factor for heart disease and stroke, its relationship to hypertension is often forgotten, vascular which were the number 1 and number 3 killers in preliminary dementia ranked eighth among the top 10 causes of death in data from the year 2004,3 regardless of whether other risk the United States in 20043and second (to Alzheimer’s disease) factors are present.4Approximately 60 million Americans have as a cause for nursing home placement. hypertension, which includes those whose blood pressure is The two major reasons for the increased prevalence of 140 mm Hg or higher systolic or 90 mm Hg diastolic and hypertension in the United States are aging and increasing those who are taking antihypertensive medications;an addi- weight of the population.These disproportionately affect the tional 5 million persons have been told twice by a health care two ends ofthe age spectrum.The fastest-growing segment of provider that their blood pressures were elevated and are the U.S.population is the “old old,”that is,those aged 85 years counted as “hypertensive” in some surveys.4,5 High blood and older.11 The prevalence of hypertension in these indi- pressure was given as a primary or contributing cause ofdeath viduals is thought to be more than 95%,because data from the in about 11% of the death certificates filed in 20034 and Framingham Heart Study put the lifetime risk of hyper- ranked 13th among primary causes of death in preliminary tension (beginning at either age 55 or 65 years) at more data from 2004.3The importance ofhypertension among the than 90%.12The current nationwide epidemic of obesity and living can also be ascertained from the preliminary 2004 physical inactivity, particularly among children and adoles- National Ambulatory Medical Care Survey, which indicated cents, makes it likely that hypertension will become even that hypertension was the most common diagnosis for a more prevalent as these overweight individuals grow into chronic disease among all outpatients: the ICD-9 code for adulthood.13 hypertension (401) was listed in more than 42 million medical The estimated cost of hypertension and its treatment office visits.6 ($63.5 billion) in the United States in 2006 is but a small part The major reason why hypertension is so important,how- of the total cost of cardiovascular disease ($403.1 billion).4 ever,is not because ofthe deaths or health care provider visits The National Committee for Quality Assurance estimates that that are directly attributed to it. Hypertension is the most in 2005,if blood pressures had been better controlled,many widespread risk factor for many other diseases and illnesses, cardiovascular events would have been prevented or delayed, each of which carries a high morbidity and mortality rate. between 12,000 and 32,000 deaths would have been avoided, Coronary heart disease, still the most common killer of and $328 million to $1 billion would have been saved.14Both American men and women,has many risk factors,but one can direct costs ofhospitalization ($6.2 billion) and nursing home make a persuasive case that, on a nationwide population- care ($3.9 billion), as well as the indirect costs ($16 billion, attributable basis, hypertension is currently more important consisting primarily of lost productivity,disability payments, than smoking, diabetes, or dyslipidemia.4 Some believe that and death benefits) would be considerably reduced. The one of the major reasons for the decline in deaths from both major driver of the increased cost of hypertension in the coronary heart disease and stroke during the past 30 years is United States over the last 15 years has been the cost of anti- the better and more effective treatment of hypertension.7 hypertensive drugs,which has risen at more than seven times Hypertension is the risk factor with the highest population- the inflation rate. The rate of rise will probably decrease attributable risk for stroke in the United States.8Heart failure, somewhat in the near future,as most of the commonly used the most common discharge diagnosis from short-stay,acute- antihypertensive drugs will become available in generic for- care hospitals for Medicare beneficiaries across the United mulations.The economics of hypertension and its treatment States, is preceded in about 85% of cases by hypertension.9 vary widely across nations, in part because some countries xvi Preface have national formularies that restrict access to expensive analysis,in Section 5.The various concomitant diseases that drugs.In some countries,even inexpensive generic formula- are often seen in hypertensive patients are summarized in tions ofantihypertensive drugs are beyond the means ofmany Section 6. Hypertension has many “special populations and patients,which is one of the challenges in controlling hyper- special situations”that are discussed in Section 7.The future tension worldwide.2 ofhypertension treatment is considered in Section 8,and the In this book, we have attempted to gather chapters that book ends with a discussion ofhypertension guidelines (from cover the most important topics in hypertension,written by several different points ofview) in Section 9. world authorities in each case.We have attempted not to avoid some ofthe current controversies in hypertension but to allow William J.Elliott,MD,PhD each author to present his or her point of view,with an eye Henry R.Black,MD toward a balanced and objective result. The discerning reader will recognize that several of the References “hot topics”in hypertension are mentioned but not dealt with in detail,for reasons ofspace and because these controversies 1. Kearney PM,Whelton M,Reynolds K,et al.Global burden of can be more effectively presented in other arenas, including hypertension:Analysis ofworldwide data.Lancet.2005;365: the very recent medical literature. For example, the growing 217-223. 2. Ezzati M,Lopez AD,Rodgers A,et al.Selected major risk awareness of the necessity of assessing global risk in a hyper- factors and global and regional burden ofdisease.Lancet. tensive patient before embarking on treatment has been skill- 2002;360:1347-1360. fully promoted15 and adopted in most of Europe16 but not 3. Miniño AM,Heron M,Smith BL.Deaths:Preliminary data for accepted in practice in the most recent U.S. guidelines.17 2004.National Center for Health Statistics,Centers for Disease Similarly,JNC 7 recommends an initial thiazide-type diuretic Control and Prevention,2006.Found on the Internet at for “most” patients with stage 1 hypertension and no com- http://www.cdc.gov/nchs/products/pubs/pugd/hestats.prelimde pelling indication for a different class of drug17; the recent aths04/preliminarydeaths04.htm,accessed 25 JUN 06. British National Institute for Health and Clinical Excellence 4. Thom T,Haase N,Rosamond W,et al.Heart disease and stroke (NICE) guidelines instead recommend either an ACE statistics—2006 update:A report from the American Heart inhibitor (for young white patients) or a calcium antagonist Association Statistics Committee and Stroke Statistics (for black or older patients).18 The NICE guidelines recom- Subcommittee.Circulation.2006;113:85-151. mend a β-blocker only for fourth-line treatment of hyper- 5. Fields LE,Burt VL,Cutler JA,et al.The burden ofadult hypertension in the United States 1999 to 2000:A rising tide. tension, based on their economic analyses and a recent Hypertension.2004;44:398-404. meta-analysis19;the low opinion ofthis class ofdrug is shared 6. Burt CW,McCaig LF,Rechtsteiner EA.Ambulatory medical by neither JNC 7 nor the author of this book’s chapter on care utilization estimates for 2004.National Center for Health β-blockers. The debate about the clinical importance of Statistics,Centers for Disease Control and Prevention,2006. incident diabetes during drug treatment of hypertension has Found on the Internet at:http://www.cdc.gov/nchs/products/ intensified since these chapters were written,20,21 but a brief pubs/pubd/hestats/estimates2004/estimates04.htm,accessed 25 review and salient references can be found in the appropriate JUN 06. chapters in this book.Whether certain classes ofantihyperten- 7. Braunwald E.Shattuck Lecture:Cardiovascular medicine at the turn ofthe millennium:Triumphs,concerns and opportunities. sive drugs have “benefits beyond blood pressure control” is still debated,22-24but some aspects of this controversy can be N Engl J Med.1997;337:1360-1369. 8. Gorelick PB,Sacco RL,Smith DB,et al.Prevention ofa first found in the chapters found within these covers. stroke:A review ofguidelines and a multidisciplinary consensus We have attempted to edit the submitted chapters to make statement from the National Stroke Association.JAMA.1999; them as balanced,fair,and objective as possible,while trying 281:1112-1120. to retain some ofthe opinion and flavor ofthe authors’points 9. Levy D,Larson MG,Vasan RS,et al.The progression from of view. We recognize, however, that errors may have crept hypertension to congestive heart failure.JAMA.1996;275: into the text, but we hope the reader will understand that 1557-1562. these were inadvertent and unintentional.Similarly,in a book 10. United States Renal Data System.2003 Annual Report.Figure ofthis scope and magnitude,there will,ofnecessity,be omis- 2.9.Found on the Internet at:http://www.usrds.org/slides.htm. Accessed 25 JUN 06. sions of important references and shortened summaries of 11. Meyer J.Age:2000 (A Census 2000 Brief;C2KBR/01-12). some individuals’opinions.We regret that it was not possible US Department ofCommerce:Economics and Statistics to make this book as all-encompassing as everyone would Administration:US Census Bureau,October,2001.Found wish. The decisions to omit some aspects of hypertension- on the Internet at:http://www.census.gov/prod/2001pubs/ related data were those ofthe authors and editors,and we take c2kbr01-12.pdf.Accessed 15 JUN 06. full responsibility for these. 12. Vasan RS,Beiser A,Seshadri S,et al.Residual lifetime risk for We have attempted to organize the book along classical developing hypertension in middle-aged women and men:The lines.Section 1 deals with the epidemiology and pathophysi- Framingham Heart Study.JAMA.2002;287:1003-1010. ology of hypertension.Section 2 is concerned with diagnosis 13. Ogden CL,Carroll MD,Curtin LR,et al.Prevalence of (including secondary hypertension) and is much longer than overweight and obesity in the United States,1999-2004.JAMA. 2006;295:1549-1555. an analogous book would have been some 20 years ago 14. National Committee for Quality Assurance.The State ofHealth because of the emerging data about ambulatory and home Care Quality,2005.Washington,DC,2005,p.12.Found on the blood pressure monitoring. Risk stratification is the major Internet at www.ncqa.org/Docs/SOHCQ_2005.pdf.Accessed 25 theme ofSection 3,whereas the usual treatment options (both JUN 06. lifestyle modifications and drugs) are presented in Section 4. 15. Jackson R,Lawes CMM,Bennett DA,et al.Treatment with Outcome studies are discussed,both in design and in meta- drugs to lower blood pressure and blood cholesterol based on