H YPERTENSION IN THE E LDERLY

H

E

Hypertension in the Elderly, edited by L. Michael Prisant,

, 2005 Lower Extremity Arterial Disease, edited by Dennis G. Caralis,

,

PhD

,

, and George L. Bakris,

, 2005

Secondary Hypertension: Clinical Presentation, Diagnosis, and Treatment, edited by George A. Mansoor,

, 2004 Pediatric Hypertension, edited by Ronald J. Portman,

,

Jonathan M. Sorof,

, and Julie R. Ingelfinger,

, 2004

C ^LINICAL H YPERTENSION AND V ^ASCULAR D ^ISEASES

W ILLIAM B. W HITE , MD

H YPERTENSION IN THE E ^LDERLY

Edited by

L. M ^ICHAEL P ^RISANT , ^MD

Medical College of Georgia, Augusta, GA

© 2005 Humana Press Inc.

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Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regu- lations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recom- mended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication.

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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 eISBN: 1-59259-911-7

Library of Congress Cataloging-in-Publication Data Hypertension in the elderly / edited by Michael L. Prisant.

p. ; cm. -- (Clinical hypertension and vascular diseases) Includes bibliographical references and index.

ISBN 1-58829-197-9 (alk. paper) 1. Hypertension in old age.

[DNLM: 1. Hypertension--drug therapy--Aged. 2. Hypertension--etiology--Aged.

3. Antihypertensive Agents--therapeutic use--Aged. 4. Clinical Trials--Aged.

WG 340 H99517 2005] I. Prisant, Michael L. II. Series.

RC685.H8H7872 2005 618.97'6132--dc22

2004019019

v

D ^EDICATION

With love to my wife,

Rose Corinth Trincher,

A CKNOWLEDGMENT

Without my mentor, Dr. Albert A. Carr, there would be no book, research, publications, teaching skills, or cognitive patient care. I was fortunate to have him as my friend and teacher.

vi

I ^N M ^EMORIAM

In memory of Dr. Ray W. Gifford, 1923–2004

Dr. Gifford was the former chairman of the Department of Hyperten- sion and Renal Disease at The Cleveland Clinic and a renowned clini- cian, pioneering researcher, leader of medical professional societies, and internationally recognized expert on the nature and treatment of hypertension, nephrology, and cardiovascular disease. As a researcher, Dr. Gifford investigated the causes and treatments of hypertension. As chairman and a member of the Joint National Committee on Detection, Evaluation and Treatment of Hypertension, he coordinated and pro- duced standards for medical professionals across America in the diagno- sis and treatment of hypertension and related disorders.

While Dr. Gifford was chairman of Hypertension and Renal Disease, he linked the Clinic’s strong research programs in the humoral, hemo- dynamic, and neurologic aspects of hypertension, with clinical programs that focused on treatment options and their benefits, as well as patient and physician education. The author of more than 460 scientific papers, and the textbook Pheochromocytoma (with William M. Manger,

), Dr. Gifford performed long-term studies of patients with hypertension, evaluated medications and surgical treatments for hypertension, con- tributed to knowledge of arteriosclerosis and aneurysms, Raynaud’s dis-

vii

ease, renal artery disease, renal transplantation, the effect of hyperten- sion on the extremities, and the effects of dietary sodium, among many other subjects.

Dr. Gifford enjoyed great rapport with his patients and was beloved by a large and loyal practice. Although he attempted to retire from the Clinic in 1993, strong demand from his patients brought him back to active practice until 1999. His influence on the discipline of hyperten- sion will be felt for many years. He will missed by his family and colleagues.

viii In Memoriam

ix

S ^ERIES E ^DITOR ’ ^S I NTRODUCTION

The importance of treating hypertension in the elderly has been greatly appreciated by physicians and scientists since the results of the Medical Research Council studies of the 1970s and the isolated systolic hyperten- sion trials SHEP and Syst-Eur that followed in the 1980s and 1990s.

Despite this appreciation of the severity of the complications of this common disorder during advancing age, treatment rates to control blood pressure in elderly patients with hypertension have been quite low. Dr.

Prisant’s volume on Hypertension in the Elderly is therefore a most clinically relevant contribution in the area of management of hyperten- sion in older people. This book brings together the basic pathophysi- ological, epidemiological, diagnostic, and therapeutic advances in the evaluation of high blood pressure in this population.

The editor, Dr. Prisant, has astutely organized this volume into sec- tions that cover age-related changes in the cardiovascular system includ- ing the development of reductions in arterial compliance, overviews of the epidemiology of hypertension in the older patient, clinical evaluation that covers a variety of topics such as blood pressure measurement and hypertensive complications characteristic of the older patient, and nonpharmacological and pharmacological approaches to the treatment of hypertension in the elderly.

Substantial coverage has been appropriately given to the impact of pharmacological treatments based on clinical trials in the elderly in Chapters 15 through 20. There are also a few chapters devoted to special patient populations that highlight problems of particular concern in older patients, including cerebrovascular disease, diabetes mellitus, heart fail- ure, and chronic arthritis. These sections contribute to the novelty of this book because they are grounded in clinical investigations that have led to enhanced understanding of the management of hypertension during advancing age. The complications of hypertension in older patients are complex, clinically challenging, and have led to much improved thera- pies targeted towards disease regression or prevention, as outlined in Chapters 12–14, and 22.

The chapters in Hypertension in the Elderly have been written by a

number of well-known, expert authors who have provided comprehen-

sive, scientifically sound, and clinically appropriate information. As

series editor of Clinical Hypertension and Vascular Diseases, I am

pleased by the publication of this timely, well-organized book and know

x Series Editor’s Introduction

that Hypertension in the Elderly will become a highly utilized textbook for all specialists in cardiovascular and geriatric medicine as well as all physicians who take care of older adults.

William B. White,

Professor of Medicine and Chief

Division of Hypertension and Clinical Pharmacology

Pat and Jim Calhoun Cardiology Center

University of Connecticut School of Medicine

Farmington, CT

P ^REFACE

Hypertension in the Elderly attempts to focus attention on the group of hypertensive patients with the largest body of outcomes trial data, but the poorest blood pressure control. Research data continue to recognize the importance of hypertension for contributing to both the morbidity and mortality of older patients. The outcomes trials document the benefits of blood pressure treatment in reducing the rate of myocardial infarction, heart failure, and stroke.

The organization of Hypertension in the Elderly is separated into basic concepts, epidemiology and trials, evaluation and management, pharmacologic treatment, special populations, and adherence. The contributors have provided detailed current information that is useful for the management of patients. Several chapters are state-of-the-art reviews that integrate a large body of information.

The four chapters in Part I impart to the reader an important overview.

The late Dr. Gifford and I underscore the importance and the challenge of treating elderly hypertensive patients. As emphasized, most elderly hypertensives in the United States and in the world are not getting the maximum benefit from antihypertensive medications. Drs. Webb and Inscho describe the physiology of the age-related changes of the cardio- renal system, and Dr. Izzo applies that information to give insight into the mechanisms of hypertension in the elderly. Age-related changes in vascular stiffness are a central factor of hypertension and target organ damage. Finally, Dr. Sica describes the pharmacological and pharmaco- dynamic changes in older patients that influence how drugs are handled.

There is merit in the clinical maxim of drug therapy in the elderly “to start low and go slow.”

Part II covers the epidemiology and trials of older patients. It is appropriate that Drs. Kannel and Wilson should remind us of the Framingham Heart Study experience. The Framingham Heart Study has always maintained the importance of systolic blood pressure as a risk factor for cardiovascular disease, a finding that has been rediscov- ered over the last 10 yr. Dr. Harrell and I methodically review the lifestyle trials in older patients. Except for TONE, most of these trials are small; thus, more work needs to be done. These data document that nonpharmacologic therapy can decrease the need for drug therapy.

Finally, I review the hypertension outcomes trials that were conducted

xi

xii Preface

in older persons. Except for ALLHAT, I have included only trials that were conducted on elderly hypertensive patients. It is my opinion that the double-blind trials provide the best data for decision making.

Part III is an ambitious section covering blood pressure measurement, clinical evaluation, secondary hypertension, and target organ damage.

Drs. Arias-Vera and White correctly point out that blood pressure deter- mination is one of the most important parts of the clinical evaluation of an older patient. Therefore, the physician must make every effort to measure blood pressure accurately. Dr. Jackson and I provide a practical approach for evaluating the elderly hypertensive patient. Dr. Isales re- ports that most endocrine causes of secondary hypertension in elderly are rare, except for thyroid disease; however, he provides a useful clini- cal approach for evaluation. Drs. Vongpatanasin and Victor provide a thoughtful approach to both renovascular hypertension and hyperten- sive renal disease. Drs. Landolfo, Thornton, Robinson, and I reviewed the heart failure trials in elderly patients and have concluded that our knowledge base is limited. Indeed, about 50% of elderly patients with heart failure have a preserved ejection fraction, for which there are scanty outcomes trials. Dr. Houghton emphasizes a comprehensive approach to risk factors in hypertensive patients with and without ischemic heart disease. Finally, Dr. Nichols examines the relationship of hypertension and various cerebrovascular events. His discussion of dementia and hypertension highlights the complexity of the relationship.

Part IV covers pharmacological therapy. The role of individual drug classes, including diuretics and β-blockers (Dr. Cushman), angiotensin- converting enzyme inhibitors (Dr. Sica), angiotensin receptor blockers (my assignment), calcium antagonists (Drs. White and Thavarajah), and α

-blockers (Dr. Pool) are described, as is how they should be used to treat the elderly hypertensive. Dr. Mulloy and I reviewed the sparse individual trials of combination drug therapy in the elderly hypertensive patients and concluded that combination drug therapy achieves a higher control rate.

Part V focuses on special populations, including African-Americans,

patients with diabetes, and patients with arthritis. Drs. Johnson and

Saunders support a more culturally sensitive approach to treating older

African-Americans. Various drug classes are evaluated. The use of the

treatment algorithm of the International Society for Hypertension on

Blacks is highlighted. Dr. Sowers and I cover the elderly diabetic hyper-

tensive. This group will enlarge and require multiple drugs to achieve

blood pressure, glucose, lipid, and antiplatelet control. Drs. Thavarajah

and White address a topic that plagues thoughtful physicians and

Preface xiii

hypertensionologists—arthritis pain control vs blood pressure control.

Clearly, we need antiarthritics that do not impair blood pressure control when acetaminophen and salicylate fail. Chronic requirements for these anti-inflammatory agents may necessitate a change in the class of anti- hypertensive agent or an up titration of current antihypertensive agents to prevent clinically significant untoward effects.

Part VI addresses adherence. Drs. Egan and Okonofua speak to the clinician’s role in improving therapeutic adherence and blood pressure control in older hypertensive patients. The behavioral science of this topic is a neglected area in the training of most health care providers.

I am grateful to the individual authors who have contributed their expertise and time to Hypertension in the Elderly with their outstanding manuscripts. I would also like to acknowledge others who have influ- enced the content of this book in various ways: Drs. George Bakris, Henry Black, Bill Elliott, Bill Frishman, Tom Giles, Marvin Moser, Suzanne Oparil, Donald Vidt, Michael Weber, and many others.

However, without my mentor Dr. Albert A. Carr, there would be no book. Humana Press was kind enough to provide the opportunity to work on this book as one of series in the field of hypertension.

I offer my first book, Hypertension in the Elderly, to the reader with some trepidation. As with any new undertaking, the feedback of the readers will improve further editions. Thus, I ask readers to forward to me your comments for any additions, omissions, or errors.

L. Michael Prisant,

xv

C ^ONTENTS

Acknowledgments ... vi

In Memoriam ... vii

Series Editor’s Introduction ... ix

Preface ... xi

Contributors ... xix

PART I: BASICS 1 The Importance of Hypertension in the Geriatric Population ... 3

Ray W. Gifford, Jr. and L. Michael Prisant 2 Age-Related Changes in the Cardiovascular System .... 11

R. Clinton Webb and Edward W. Inscho 3 Aging, Arterial Stiffness, and Systolic Hypertension ... 23

Joseph L. Izzo, Jr. 4 Pharmacological and Pharmacodynamic Alterations in the Elderly: Application to Cardiovascular Therapies ... 35

Domenic A. Sica PART II: EPIDEMIOLOGY AND TRIALS 5. Epidemiology of Hypertension in the Older Patient ... 53

William B. Kannel and Peter W. F. Wilson 6. Nonpharmacological Trials in the Older Hypertensive Patient ... 69

L. Michael Prisant and Dean U. Harrell

7. Clinical Trials of Hypertension in the Older

Patient ... 91

L. Michael Prisant

xvi Contents

PART III: EVALUATION AND MANAGEMENT 8. Blood Pressure Measurement in Older Patients

With Hypertension ... 119 Jose Ramiro Arias-Vera and William B. White 9. Clinical Evaluation of the Elderly Hypertensive ... 135

L. Michael Prisant and Thomas W. Jackson 10. Hypertension in the Elderly: Endocrine Causes

of Secondary Hypertension ... 145 Carlos M. Isales

11. Diagnosis and Management of Hypertensive Renal and Renovascular Disease in the Elderly ... 171 Wanpen Vongpatanasin and Ronald G. Victor 12. Heart Failure in the Older Hypertensive Patient ... 197

L. Michael Prisant, Carolyn Landolfo,

John Thornton, and Vincent J. B. Robinson 13. Ischemic Heart Disease in the Older Hypertensive

Patient: Evaluation and Management ... 229 Jan Laws Houghton

14. Cerebrovascular Disease in the Elderly

Hypertensive ... 255 Fenwick T. Nichols III

PART IV: PHARMACOLOGICAL MANAGEMENT 15. Diuretics and β-Adrenergic Blockers

in the Management of Hypertension

in the Elderly ... 297 William C. Cushman

16. Assessment of the Role of ACE Inhibitors

in the Elderly ... 321 Domenic A. Sica

17. Use of Angiotensin Receptor Blockers

in the Elderly ... 349 L. Michael Prisant

18. Clinical Trials With Calcium Antagonists in Older

Patients With Hypertension ... 369

William B. White and Sumeska Thavarajah

19. α-Adrenoceptor Blockers for Management

of Hypertension in the Elderly ... 381 James L. Pool

20. Combination Drug Therapy in the Elderly ... 399 L. Michael Prisant and Laura Lyngby Mulloy

PART V: SPECIAL POPULATIONS

21. Attitudes Regarding Hypertension Among Older

African-American Adults ... 429 Wallace R. Johnson, Jr. and Elijah Saunders 22. Treatment of Hypertension in the Elderly Patient

With Diabetes ... 451 James R. Sowers and L. Michael Prisant

23. Management of Hypertension in Older Patients

With Arthritis ... 471 Sumeska Thavarajah and William B. White

PART VI: ADHERENCE

24. The Clinician’s Role in Improving Therapeutic Adherence and Blood Pressure Control

in Older Hypertensive Patients ... 493 Brent M. Egan and Eni C. Okonofua

Index ... 517

Contents xvii

xix

C ONTRIBUTORS

J

R

A

-V

,

• Rhode Island Department of Corrections, Warwick, RI

W

C. C

,

• Department of Preventive Medicine and Medicine, University of Tennessee College of Medicine and Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, TN

B

M. E

,

• Department of Medicine and Pharmacology, Medical University of South Carolina, Charleston, SC

R

W. G

, J

.,

• Department of Nephrology and Hypertension, Cleveland Clinic Foundation, Cleveland, OH

D

U. H

,

• Senior Health Center, Department of Medicine, Medical College of Georgia, Augusta, GA

J

L

H

,

• Division of Cardiology, Albany Medical College, Albany, NY

E

W. I

,

• Department of Physiology, Medical College of Georgia, Augusta, GA

C

M. I

,

,

• Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA

J

L. I

, J

.,

• Division of Clinical Pharmacology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY

T

W. J

,

• Senior Health Center, Department of Medicine, Medical College of Georgia, Augusta, GA

W

R. J

, J

.,

• Section of Hypertension, University of Maryland School of Medicine, Baltimore, MD

W

B. K

,

,

• Department of Medicine and Public Health, Boston University School of Medicine; Framingham Heart Study, Framingham, MA

C

L

,

,

• Section of Cardiology, Department of Medicine, Medical College of Georgia, Augusta, GA

L

L

M

,

,

• Section of Nephrology, Hypertension,

and Transplantation, Department of Medicine, Medical College

of Georgia, Augusta, GA

F

T. N

III,

,

• Department of Neurology, Medical College of Georgia, Augusta, GA

E

C. O

,

• Department of Medicine, Medical University of South Carolina, Charleston, SC

J

L. P

,

• Departments of Medicine and Pharmacology, Baylor College of Medicine, Houston, TX

L. M

P

,

,

,

,

• Hypertension and Clinical Pharmacology, Department of Medicine, Medical College of Georgia, Augusta, GA

V

J. B. R

,

,

• Section of Cardiology, Department of Medicine, Medical College of Georgia, Augusta, GA

E

S

,

• Section of Hypertension, University of Maryland School of Medicine, Baltimore, MD

D

A. S

,

• Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA J

R. S

,

,

,

,

• Department of Internal

Medicine, University of Missouri Health Care, Columbia, MO S

T

,

• Department of Nephrology, John

Hopkins School of Medicine. Baltimore, MD

J

T

,

,

• Section of Cardiology, Department of Medicine, Medical College of Georgia, Augusta, GA

R

G. V

,

• Hypertension Division, University of Texas Southwestern Medical Center, Dallas, TX

W

V

,

• Divisions of Hypertension and Cardiology, University of Texas Southwestern Medical Center, Dallas, TX

R. C

W

,

• Department of Physiology, Medical College of Georgia, Augusta, GA

P

W. F. W

,

• Department of Endocrinology, Diabetes, and Medical Genetics, General Clinical Research Center, Medical University of South Carolina, Charleston, SC

W

B. W

,

• Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT

xx Contributors