Atlas of Heart Diseases: Hypertension: Mechanisms and Therapy PDF
Preview Atlas of Heart Diseases: Hypertension: Mechanisms and Therapy
This educational resource has been provided as a service to the medical community by AstraZeneca. maker of ATACAND® (candesartan cilexetil) and ATACAND HCrM (candesartan cilexetil-hydrochlorothiazide). Please see accompanying full Prescribing Information. including boxed WARNING regarding use in pregnancy. ~ AstraZeneca ~ Atlas of - - - HEART DISEASES Hypertension: Mechanisms and Therapy THIRD EDITION volume editor NORMAN K. HOLLENBERG, MD, PHD Professor of Radiology Harvard Mcdlc.J1 School DireClor. Physiologic Research Department of Medlcin!;! Brigham and Woml.'n's Hospilal BasIon, fI:lassachusctts Se ri es edito r EUGENE BRAUNWALD , MD, MD (HON), SeD (HON) Vice President for Academic Programs. Partners t-IcallhCarc System Distinguished I h:rscy Profcssor of the Theory .:md Practice of ""Icdiclnc Faculty Dcan for ,\eademlc Programs Brigham .:md Women's Hospllal and Massachus('IIS Gener.11 lIospital H.lrvard Medical School Basion. MJssilchusctls With 22 Contributors eM nJRR~ Ml.DICINl. Developed by Current Medicine, Inc., Philadelphia CURRENT MEDICI NE 400 MARf-ET STREfT. SUITE 700' PHILADELPHIA, PA 19106 Managing Editor ........................................ .cJwrles Fie/d Developmental Editors ........................... Lisa M. Jallda, alld Marimi BeI/lis Editorial Assistant.. ........................A IIII11/arie O'Orlolla Art Director ........................................... Jerilyll Kauffillall Design and Layout .................................J e11l1ifer Kllighl nJustration Director ..............................A IIII Saydlowski Illustrators .................................................... Marie Deali, AIIII Saydlowski, alld LnrnJ Ward Production Director .................................... Lnri Hol/alld Assistant Production Manager. ..............S imoll OickClJ Indexing ..........................................A lexalldrn Nickersoll Hypertension: mechanisms andt herapy / volume editor, Norman K. Hollenberg. - 3rd ed. p. ; cm. - (Alias of heart d iseases) Includes bibliographic references and i ndex. 1. Hypertcnsion-Atlases. 1. Hollenberg, Norman K. II. A lais of heart diseases (Unnumbered) IDNLM: 1. Hypertension-physiopathology-allases. 2. Hypertension-therapy-atlases. WG 17 H998 20001 RC685.H8 H825 2000 616.1'32dc21 for library of Congress 00-023233 CIP Library of Congress Cataloguing-in-Publication Data ISBN 978-1-4684-6911-0 ISBN 978-1-4684-6909-7 (eBook) DOI 10.1007/978-1-4684-6909-7 () Copyright 2001 by Springer Science+Business Media New York. AII rights reserved. No part or this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means electronic, mechanical, photocopying, recording, or otherwise, without prior written consent of the publisher. Originally published by Current Medicine in 2001 Softcover rellrint or the hardcover 3rd edition 2001 1098 76543 " CONTRIBUTORS R. WAYNE ALEXANDER, MD, PHD WILLIAM J. ELLIOTT, MD, PHD R. Brllce Logue Professor of Medicillf! Professor Director of Cardiology Department of Preventive Medicine Emory Ulliversity Rush Medical College Atfa/lfn, Georgia Attending Pllysiciall Rllsh-Presbyteriall-St. Luke's Medical Center JOHN AMERENA, MBBS, FRACP Chicago, lllillois SCllior Lectllrer Depar/me,,! of Medicille KATHY K. GRIENDLlNG, PHD University of Melbourne Professor of Medicille Gee/OIlg Hospital Department of Medicille/Cardiology Gee/ollg, Australia Emory Ulliversity Atlanta, Georgia HENRY R. BLACK, MD Charles f. mId Margaret Roberts Professor and CARLENE MINKS GRIM Cltainl1{1ll Shared Care Researdl alld Educatioll Departmellt of Preventive Medicine Torrallce, Califomia Rush Medical College CLARENCE E. GRIM Associate Vice Presidellt for Rl..'Search Professor RlIs},-Presbyleriml-Sf. Luke's Medical Cellter Departmellt of Cardiovascular Medicille Chicago, Illillois Medical College of Wisconsi" EMMANUEL L. BRAVO, MD Milwaukee, Wiscollsi/l Department of Nephrology a/ld Hypertellsion RANDOLPH A. HENNIGAR, MD, PHD The Cleveland Clillie FOIlI1dntioll Associate Professor of PatilOlogy Cleve/alld, Ohio Departmellt of Pathology HANS R. BRUNNER, MD Emory University Professor of Medicine Atlallta, Georgia Dillisioll of HypertcIIsioll NORMAN K. HOLLENBERG, MD, PHD La/lSl1//lfC University Professor of Radiology Ulliversity Hospital Departmel/t of Medici/Ie WI/sa/me, Switzer/fl/ld Harvard Medical School Director, Physiologic Researdl ROBERT M. CAREY, MD Professor of Medicine Brig/mill alld Women's Hospital BostOll, Massad/llsetts Dean, SeI/Ool of Medicillc U"iversily of Virgil/in Health Sciences Cellter Clmrlottesville, Virginia "' STEVO JULIUS, MD, SeD HELMY M. SIRAGY, MD, FRACP Profi'~sor of lull'rIml Medicine "lid Plty:;;ology Professor of Medicil/e Frede,;ck C.L. H,lehllel/ Professor Dl'pnrtmel/t of Medicil/e of Hyperle1lsioll Ullilll'rsity of Virgil/ia Departlllellt of '"/ernal Medicine CJmrlottesuille, Virgil/in Ulliversity of Miclligall BERNARD WAEBER, MD AIIII Arbor, Middgn" Professor of Medicille WILLIAM B. KANNEL, MD, MPH DepnrtmC'I/t of Medici/Ie Professor of Medici"e "lid Pllhlic Health wI/Sflm/C' UIlil.lCrsity Bostoll U"iversity School of Medicille Ulliuersity Hospital LaIlSflmIe, Switzer/mId Boslol/, Massad/lise/Is SmioT Investigator ALAN B. WEDER, MD Frnm;IIgllflm Study Professor of Medicine Framillglmm, Massad/usetls Department of 11111..'",01 Medicine BARRY j. MATERSON, MD, MBA rhe U"iuersity of Michigan Medical CClfter Professor of Medici"e An" Arbor, Micltigall Depur/mell' of Medicine MATIHEW R. WEIR, MD Ulliversi/y of Miami Professor of Medicine Miami, Florida Director, Division of Nephrology and Clillical Research Unit JAMES A. SCHOENBERGER, MD Department of Medicil/e Emeritlls Proft!ssor of Medicille Divisioll of Nephrology Drpar/mel//s of Medicille nlld Preve1ltive Medicine Ulliversity of Maryla/ld School of Medicille RIIsh-Presbyleriall-St. Lllke's Medical Cellier Baltimore, Marylalld Cllicngo, Illinois GORDON H. WILLIAMS, MD DOMENIC A. SICA, MD Professor of Medicille Professor Departmellt of Medici"e Harvard Medical ScI,ool Depar/mt'''' of Medicine alld Plmrmacology Chief, Endocrille-Hypertensiotl Division CllI7irmflll. Clinical Pharmacology fwd Hypertellsioll Brigham and Womeu's Hospital Medical College of Virgil/in 80stOIl, Massachusetts RiclllllOlld, Virginia iv PREFACE Although It '-;('Cms like only yesterday, it ha ... banded out...tanding units devoted to the oc'Cn 6 year. .. .,ince the first edition wa ... pre development of antihyperten~ives. ThoM.' pared, and almost 3 years since the <;ccond. who ignored the conventional wisdom, as is The atlas format, applied to the problem of often the case, prospered. hypertenSion, has proven to be very attractive This created a problem. How could we to readers of both the first and second edition. develop a detailed overview on the Angll We have learned a lot while preparing the Antagonist class, vasopcptidasc inhibitors, Atlas, and we are confident that readers of the and new ilgents available for blocking aldos third edition will find it to be improved. terone-with all of their therapeutic implica Cardiovascular medicine is moving at a tions-without distorting and overloading a vcry rapid pace, and hypertension is no chapter on drug therapy, prepared so well by exception. All of the chapters have been Drs. Wncber and Brunner? The solution was updated and incorporate new information. to have Drs. Wacher and Brunner focus on The new figures and legends have not simply therapeutics, while maintaining their empha been added to the end of the chapters, as a sis on the agents that have been available for kind of caboose, but rather have been fitted some time. They added new information 011 into the narrative in what we hope is a seam the newer drugs that have reached what less manner. might be called "therapeutics." Dr. Domcnic Additionally, we have included two new Sica contributed the second new chapter, chapters. Dr. Clarence Grim pointed out that which places emphasis on the pharmacology, an atlas of hypertension ought to include at clinical pharmacology, and early therapeutics least something on blood pressure measure in the arca of the new drug classes. We believe ment. He was, of course, absolutely correct, this solution not only divides the workload, and has contributed a new chapter that pro but also makes it easier for the physician to vides detailed information on the "how to" of find the information that he or she needs. correct blood pressure measurement. One hope expressed in the preface to the While considering the second new chapter, first edition, and echoed in the preface to the we faced another fundamental issue in plan second, is that a single chapter on pathophys ning this edition. The area of drug therapy has iology would be all that would be required shown continued, major growth. This is par because our understanding of pathogenesis ticularly interesting in view of the widely held had become so complete. Alas, that wish has conventional wisdom of the early 1990s that not been met. Perhaps in the next edition ... ? patients with hypertension were already well served, and there would be little advance in drug therapy. Indeed, some companies dis· Norman K. Hollenberg, MD, PhD v CONTENTS CHAPTER 1 Pathogenesis of Hypertension: Genetic and Environmental Factors Alall B. Werler .............. ,., ........................... .. . ...... ..... . . 1 - 33 CHAPTER 2 Role of the Nervous System in Human Hypertension }olm Amerr1la (Iud Stevo jll/iIlS . ... .. .... .. , .... .. ... .. ..... .... ,. , ..... . ... 34 - 58 CHAPTER 3 Hypertension: Kidney, Sodium, and the Renin-Angiotensin System Helmy M. Siragy and Robert M. Carey .... .... ... .. .. .. ..... ... .............. 59 - 79 CHAPTER 4 Pathogenesis of Hypertension Kathy K. GriclIdl;lfg, R. WaYlle Alexander, alf(l Randolph A. Hennigar .......... .. 80 - 99 CHAPTER 5 Cardiovascular Risk Assessment in Hypertension William 8. Kannel .............................. , ............•........ . . 100 - 117 CHAPTER 6 Secondary Hypertension: Adrenal and Nervous Systems ( ""'Wlllle! L. Bravo ... ... .. ..... .................. .. .......... .. .. ...... 118 - 143 CHAPTER 7 Antihypertensive Agents: Mechanisms of Drug Action Benlaril Waeber and Harts R. Brullller ............ ........... . ..... ..••.... 144 - 161 CHAPTERS The Therapeutic Trials lames A. Schoenberger ....... .•• •. ..••••.. ... •.. ....••......•.......... . 162 - 184 vi CHAPTER 9 Antihypertensive Therapy: Patient Selection and Special Problems Barry ,. Materso" .... . .. .. . .. .. . ...... . .. .. ... .. .. .... . .. . .. ........ . .. . 185 - 207 CHAPTER 10 Antihypertensive Therapy: Progression of Renal Injury Matthew R. Weir ... ..... ..... ....... ..... ......... ......... .••••....... 208 - 236 CHAPTER 11 Antihypertensive Therapy: Compliance and Quality of life Gordon H. Williams .... ...... ........ ...... ....... .. ..... ....... ....... 237 - 251 CHAPTER 12 Special Situations in the Management of Hypertension William J. Elliott and Henry R. Black .......... ............ .....••... •..... 252 - 274 CHAPTER 13 Recommendations of the American Diabetes Association and Summary of the Joint National Committee ONC)-V and Who/International Society of Hypertension (ISH) Special Reports Nannan K. Hollenberg ..... .. ... .. .. .. .. . .. ... .. .... .. . .. ... .. .. .. ... .. .. 275 - 292 CHAPTER 14 Newer Antihypertensive Agents: Angiotensin-Receptor Antagonists and Dual Metalloproteinase Inhibitors Domen;c A. Sica .. .. ... .. ... .. .. .... . ....... ....... .. ..... .. ... .. .. .. ... 293 - 313 CHAPTER 15 Accurale and Reliable Blood Pressure Measurement in the Clinic and Home: The Key to Hypertension Control Clarence E. Grim and Carlene Minks Grim .. . ..... .. .. ... .. .. ... .. .. .•.. ... . 314 - 324 vii PATIIOGENESIS OF HYPERTENSION: GENETIC AND ENVIRONMENTAL FACfORS Alan B. Weder Like obesity and diabetes, essential hypertension is one of the "diseases of civilization" that results from the collision of a modem Lifestyle with Paleolithic genes. Genetic analyses of communities, families, twins, and individuals aU support the tenet of a genetic contribution to blood pressure regulation, but the identification of specific genes that cause hypertension has only just begun. The use of segregating populations derived from inbred hypertensive and normotensive animals, which permits tracing the linkage of genetic markers with blood pressure, has led to the detection of several genes that may contribute to hypertension. It was hoped that such studies would identify candidate genes that cause essential hypertension, but none of the specific genes identified in rat models has been proven to cause disease in humans. The applicability of congenic and transgenic methods to rats has permitted studies of candidate loci and individual genes in relatively well-defined settings, and it is hoped that such models will define the effects of mutant genes on the control of blood pressure. It should not be assumed that the effects of single-gene insertions or knockouts of candidate alleles will always have straightforv.rard phenotypic effects. An example is the hypertensive rat created by insertion of the mouse renin gene. These rats are characterized by low levels of plasma renin and renal renin gene expression but also by high adrenal renin gene expression and fulminant hypertension. Such unpredictable phenotypic effects arising from seemingly "simple" genetic manipulations serve to emphasize the complexity of genomic dynamiCS. The task of identifying genes that contri.bute to essential hypertension in humans is a great challenge, and the genetic architecture of human hypertension is only dimly perceived. Several notable successes have been achieved recently, however. The rare mendelian-dominant hypertensive syndrome of gluco corticoid~remediable hyperaldosteronism has been proven to result from a genetic chimerism of the genes for l1~~hydroxylase and aldosterone synthase, and i.t is likely that other mendelian defects associated with hypertension can be approached through use of similar methods. The more difficult problem of essential hypertension has also witnessed progress lately with the recently described link between the angiotensinogen gene and both essential hypertension and hypertension of pregnancy. A major problem in defining the genetics of essential hypertension is heterogeneity of the phenotype, and further advances may depend on refinements in subtyping hypertension. In addition to classic characterizations based on measurements of biochemical regulators of cardiovascular function, promising approaches factors can rightly focus on factors that are universally include subtyping by membrane transport character active in societies (eg, high salt intake, calorie excess, and istics and definitions based on multivariate hypertension social stress) as well as specific factors (eg, alcohol excess) related syndromes. whose impacts are limited to at-risk individuals. There may Regardless of its genetic substrate, hypertension is clearly be genetic subtypes of hypertensive individuals who are an ecogenic disease, that is, environmental factors interact particularly sensitive to specific environmental factors, for with genes to result in high blood pressure. Because the example, dietary sodium and calcium, although inter prevalence of hypertension is directly related to the mean ventional studies have not yielded conclusive evidence on blood pressure of the population, studies of environmental which to base preventive approaches to hypertension. .. { w;~~{~;: ': ~ GENETIC FACTORS IN HYPERTENSION J.~.~. .(.. ~ .~:...v . -..~~"" . FIGURE 1-1. A model indicating the mechanisms by which essential hyper Determinants of hypertension tension could result from the combined GRA effects of individual major genes that have Angiotensin a large impact on blood pressure, blended Diabetes Major genes Kallikrein polygenes with small individual contribu Obesity Na-Li counter- Polygenes Race tions, and environmental effects operating transport? Blood pressure on individuals or within families. FCHL Haptoglobin Major gene traits: familial combined hyperlipidemia; FDH MN blood type RBC Na Background familial dyslipidemic hypertension; GRA Combination Na-K cotransport? glucocorticoid-remediable aldosteronism. FDH? FCHL? (Courtesy of Roger R. Williams, MD.) Nonmodulation? i Sympathetics? Environment Individual Others? Shared Diet Oral contraceptives Na Pb Physical inactivity K Fat Stress CI Calories Lower education Ca Alcohol Small family size Mg Caffeine FIGURE 1-2. From the late 1940s through the 1960s, Sir George Pickering and Lord Platt of Grindleford debated the nature of the genetic Plan Pickering basis of human essential hypertension. Platt, a prominent English irttemist, poirtted to ~ormotensives what he believed to be discontinuities in the Normotensives ~ distribution of blood pressure values irt ~~rtensives families of hypertensive individuals and - postulated the existence of a major gene for , \ "I, hypertension, transmitted as a mendelian :: '\., "" '-\ ,, ,' -I~, dominant trait [1]. Pickering, who mam , tairted that hypertensives have blood pres :" '\ ',., ' '., . ,, , , , sures irt the upper end of a continuous, ,,, ',, ,' \, ,, smooth distribution, argued that hyperten , , \. ' sion is a multigenic disease [2). In such a ,I ," ,\. , ,, , , construct, each gene has a small effect on a , , ~/A trait (intermediate phenotype) that contri butes to irtcreased blood pressure; the sum of all the trait effects, when sufficient to zz elevate blood pressure to some arbitrarily Major Major AA aa BB bb zz gene gene Trait A Trait B Trait Z high value, is the genetic basis of essential hypertension. The consensus now supports Intermediate phenotypes Pickering's view, but the debate was of most importance because it sparked interest irt the genetic basis of human essential hypertension. H YPERTENSION: MECHANISMS AND THERAPY 2
The list of books you might like
