DIABETES AND CARDIOVASCULAR DISEASE
SECOND EDITION
CHRISTOPHERP. CANNON,MD SERIES EDITOR
C ONTEMPORARY C ARDIOLOGY
Diabetes and Cardiovascular Disease, Second Edition, edited by Michael T. Johnstone, MD,
CM,FRCP(C) and Aristidis Veves, MD,DSc, 2005 Cardiovascular Disease in the Elderly, edited by
Gary Gerstenblith, MD, 2005
Platelet Function: Assessment, Diagnosis, and Treatment, edited by Martin Quinn, MB BChBAO,
PhD and Desmond Fitzgerald, MD,FRCPI, 2005 Angiogenesis and Direct Myocardial
Revascularization, edited by Roger J. Laham,
MD and Donald S. Baim, MD, 2005 Interventional Cardiology: Percutaneous
Noncoronary Intervention, edited by Howard C. Herrmann, MD, 2005
Principles of Molecular Cardiology, edited by Marschall S. Runge, MD and Cam Patterson,
MD, 2005
Heart Disease Diagnosis and Therapy: A Practical Approach, Second Edition, edited by M.
Gabriel Khan, MD,FRCP,FRCP(C),FACC, 2005 Cardiovascular Genomics: Gene Mining for
Pharmacogenomics and Gene Therapy, edited by Mohan K. Raizada, PhD, Julian F.
R. Paton, PhD, Michael J. Katovich, PhD, and Sergey Kasparov, MD,PhD, 2005
Surgical Management of Congestive Heart Failure, edited by James C. Fang, MD
and Gregory S. Couper, MD, 2005
Cardiopulmonary Resuscitation, edited by Joseph P. Ornato, MD,FAP,FACC and Mary Ann Peberdy,MD,FACC, 2005
CT of the Heart: Principles and Applications, edited by U. Joseph Schoepf, MD, 2005 Heart Disease and Erectile Dysfunction, edited by
Robert A. Kloner, MD,PhD, 2004 Cardiac Transplantation: The Columbia
University Medical Center/New York- Presbyterian Hospital Manual, edited by Niloo M. Edwards, MD, Jonathan M. Chen,
MD and Pamela A. Mazzeo, 2004
Coronary Disease in Women: Evidence-Based Diag- nosis and Treatment, edited by Leslee J. Shaw,
PhD and Rita F. Redberg, MD,FACC, 2004 Complementary and Alternate Cardiovascular
Medicine, edited by Richard A. Stein, MD
and Mehmet C. Oz, MD, 2004
Nuclear Cardiology, The Basics: How to Set Up and Maintain a Laboratory, by Frans J. Th.
Wackers,MD,PhD, Wendy Bruni, BS,CNMT, and Barry L. Zaret, MD, 2004
Minimally Invasive Cardiac Surgery, Second Edition, edited by Daniel J. Goldstein, MD
and Mehmet C. Oz, MD 2004
Cardiovascular Health Care Economics, edited by William S. Weintraub, MD, 2003 Platelet Glycoprotein IIb/IIIa Inhibitors in
Cardiovascular Disease, Second Edition, edited by A. Michael Lincoff, MD, 2003 Heart Failure: A Clinician’s Guide to Ambulatory
Diagnosis and Treatment, edited by Mariell L. Jessup, MD and Evan Loh, MD, 2003 Management of Acute Coronary Syndromes,
Second Edition, edited by Christopher P.
Cannon,MD 2003
Aging, Heart Disease, and Its Management:
Facts and Controversies, edited by Niloo M. Edwards, MD, Mathew S. Maurer, MD, and Rachel B. Wellner, MPH, 2003 Peripheral Arterial Disease: Diagnosis and
Treatment, edited by Jay D. Coffman, MD
and Robert T. Eberhardt, MD, 2003 Cardiac Repolarization: Bridging Basic and
Clinical Science, edited by Ihor Gussak, MD,
PhD, Charles Antzelevitch, PhD, Stephen C.
Hammill,MD, Win K. Shen, MD, and Preben Bjerregaard,MD,DMSc, 2003
Essentials of Bedside Cardiology: With a Complete Course in Heart Sounds and Murmurs on CD, Second Edition, by Jules Constant,MD, 2003
Primary Angioplasty in Acute Myocardial Infarc- tion, edited by James E. Tcheng, MD, 2002 Cardiogenic Shock: Diagnosis and Treatment,
edited by David Hasdai, MD, Peter B.
Berger,MD, Alexander Battler, MD, and David R. Holmes, Jr., MD, 2002
Management of Cardiac Arrhythmias, edited by Leonard I. Ganz, MD, 2002
Diabetes and Cardiovascular Disease, edited by Michael T. Johnstone, MD and Aristidis Veves,MD,DSc, 2001
D IABETES
AND C ARDIOVASCULAR
D ISEASE
Second Edition
Edited by
M
ICHAELT. J
OHNSTONE,
MD,
CM,
FRCP(
C) A
RISTIDISV
EVES,
MD,
DScBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
© 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 regulations, 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 recommended 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.
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Cover Illustration: From Fig. 2 in Chapter 22, "Peripheral Vascular Disease in Patients With Diabetes Mellitus," by Bernadette Aulivola, Allen D. Hamdan, and Frank W. LoGerfo.
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Library of Congress Cataloging-in-Publication Data
Diabetes and cardiovascular disease / edited by Michael T. Johnstone and Aristidis Veves.-- 2nd ed.
p. cm. -- (Contemporary cardiology) Includes bibliographical references and index.
ISBN 1-58829-413-7 (alk. paper)
1. Diabetic angiopathies. 2. Cardiovascular system--Diseases--Etiology.
I. Johnstone, Michael T. II. Veves, Aristidis. III. Series: Contemporary cardiology (Totowa, N.J. : unnumbered)
RC700.D5D524 2005 616.4'62--dc22
2005000629
D
EDICATIONTo my daughters, Jessica and Lauren, and my mother Rose for their patience, love, inspiration, and support.
—MTJ
To my parents and my wife Maria.
—AV
P
REFACE TO THEF
IRSTE
DITIONvii
The cause of diabetes mellitus is metabolic in origin. However, its major clinical manifestations, which result in most of the morbidity and mortality, are a result of its vascular pathology. In fact, the American Heart Association has recently stated that,
“from the point of view of cardiovascular medicine, it may be appropriate to say, diabetes is a cardiovascular disease” (1). But diabetic vascular disease is not limited to just the macrovasculature. Diabetes mellitus also affects the microcirculation with devastating results, including nephropathy, neuropathy, and retinopathy. Diabetic nephropathy is the leading cause of end-stage renal disease in the United States, while diabetic retinopathy is the leading cause of new-onset blindness in working-age Americans.
The importance of this text on Diabetes and Cardiovascular Disease is evident by the magnitude of the population affected by diabetes mellitus. Over 10 million Americans have been diagnosed with diabetes mellitus, while another 5 million remain undiagnosed.
The impact from a public health perspective is huge and increasing. As the population of the United States grows older, more sedentary, and obese, the risk of developing diabetes and its complications will increase.
Epidemiological studies have identified diabetes mellitus as a major independent risk factor for cardiovascular disease. Over 65% of patients with diabetes mellitus die from a cardiovascular cause. The prognosis of patients with diabetes mellitus who develop overt clinical cardiovascular disease is much worse than those cardiovascular patients free of diabetes mellitus.
The 24 chapters of Diabetes and Cardiovascular Disease focus on either clinical or basic aspects of diabetes and cardiovascular disease. Part I, Pathophysiology, reviews the mechanisms and risk factors for diabetic cardiovascular disease. Part II focuses on the heart in diabetes mellitus, including coronary artery disease and congestive heart failure.
The peripheral vascular system is the subject of Part III, which addresses epidemiology, mechanisms, methods of assessment, and treatment of this macrovascular disease. Lastly, Part IV reviews the different microvascular effects in individuals with diabetes mellitus, including retinopathy, nephropathy, neuropathy, and microcirculation of the diabetic foot.
The aim of Diabetes and Cardiovascular Disease is to serve as a comprehensive review of both the basic and clinical aspects of diabetic vascular disease for the practicing clinician. The readership will include cardiologists, general internists, vascular special- ists, family physicians, and medical students, along with other interested practitioners and allied health personnel. The text is also directed toward both clinical and basic research scientists, and emphasis has thus been given to both theoretical and practical points. Each chapter covers its topics in great detail and is accompanied by extensive references.
We are indebted to the many people who worked on this volume. In particular, we wish to thank those talented and dedicated physicians who contributed the many chapters in this text. We were fortunate to have the collaboration of a group of authors who were among the most prominent in their respective fields. We hope that our efforts will serve as a stimulus for further research in this increasingly important health concern.
viii Preface to the First Edition
We want to extend our deepest appreciation to Paul Dolgert and Craig Adams of Humana Press for guiding us through the preparation of this book. As well, we want to give a special thanks to Dr. Christopher Cannon, who saw the need for such a volume and gave us the opportunity to edit this text.
Michael T. Johnstone, MD
Aristides Veves, MD,DSc
REFERENCE
1. Grundy SM, Benjamin IJ, Burke GL, et al. AHA Scientific Statement-Diabetes and Cardiovascular Disease. Circulation 1999;100:1134-1146.
P
REFACEix
It has been only four years since the first edition of this very successful text, Diabetes and Cardiovascular Disease. During this time, interest in diabetes mellitus as a risk factor for cardiovascular disease has increased logarithmically, having been the subject of many studies now found in the cardiology literature as well as American Heart Association statements in Circulation. This higher level of attention is only a reflection of the increas- ing obesity and diabetes mellitus epidemic that continues to build in Western societies, and in particular, the United States.
With the substantial increase in information resulting from this research and the ever- increasing numbers of people afflicted by diabetes mellitus, the need for a text that summarizes the information obtained, diagnostic and therapeutic guidelines becomes increasingly important. We believe our second edition mirrors the increased attention focused on this disease process, which affects about 16 million people in the United States alone.
With this burgeoning interest in diabetic cardiovascular disease, it is challenging to keep up with all the important developments in the area. In an effort to do so, we have made significant changes to this second edition. All the chapters have been updated and new ones have been added. In particular, the chapters on hypertension and dyslipidemia, as well as heart failure, and coronary artery disease and diabetes mellitus have undergone extensive “makeovers.”
We have reorganized the chapters, putting the basic science chapters in the first half of the text, with the clinical chapters now in the second half. We have moved the chapters on diabetes and dyslipidemia and hypertension to the clinical section of the text. The last chapter, “Diabetes Mellitus and Coronary Artery Disease,” has not only been signifi- cantly redone, it is now at the end of the text in an effort to serve as a summary of the clinical macrovascular disease chapters.
In the basic section, we have added chapters on diabetes mellitus and PPARs by Dr.
Plutzky, and PARP activation and the nitrosative state by Drs. Pacher and Szabó. The role of estrogens in diabetic vascular disease is discussed by Drs. Tsatsoulis and Economides, and finally the effect of adipocyte cytokines in the development of diabetes mellitus is discussed. On the clinical side, we have added chapters on interventional therapy in cardiac and peripheral vascular disease by Drs. Lorenz, Carrozza, and Garcia, as well as a chapter on cardiovascular surgery in diabetes by Drs. Khan, Voisine, and Sellke.
We again want to thank Craig Adams, Developmental Editor, and Paul Dolgert, the Editorial Director at Humana Press, as well as their office staff for their assistance in putting together this text. Also we want to give again a special thanks to Dr. Christopher Cannon whose vision it was to include such a text in the Contemporary Cardiology series.
Michael T. Johnstone, MD
Aristidis Veves, MD,DSC
xi
C
ONTENTSPreface to the First Edition ... vii Preface ... ix Contributors ... xv
PARTI. PATHOPHYSIOLOGY
1 Effects of Insulin on the Vascular System ... 1 Helmut O. Steinberg
2 Effects of Diabetes and Insulin Resistance on Endothelial Functions ... 25 Zhiheng He, Keiko Naruse, and George L. King
3 Diabetes and Advanced Glycoxidation End-Products ... 47 Melpomeni Peppa, Jaime Uribarri, and Helen Vlassara
4 The Renin–Angiotensin System in Diabetic Cardiovascular
Complications ... 73 Edward P. Feener
5 PPARs and Their Emerging Role in Vascular Biology, Inflammation,
and Atherosclerosis ... 93 Jorge Plutzky
6 Diabetes and Thrombosis ... 107 David J. Schneider and Burton E. Sobel
7 Role of Estrogens in Vascular Disease in Diabetes: Lessons
Learned From the Polycystic Ovary Syndrome ... 129 Agathocles Tsatsoulis and Panayiotis Economides
8 Poly(ADP-Ribose) Polymerase Activation and Nitrosative Stress
in the Development of Cardiovascular Disease in Diabetes ... 167 Pál Pacher and Csaba Szabó
9 Adiponectin and the Cardiovascular System ... 191 Suketu Shah, Alina Gavrila, and Christos S. Mantzoros
10 Nitric Oxide and Its Role in Diabetes Mellitus ... 201 Michael T. Johnstone and Eli Gelfand
11 Diabetes and Atherosclerosis ... 225 Maria F. Lopes-Virella and Gabriel Virella
12 The Use of Animal Models to Study Diabetes and Atherosclerosis
and Potential Anti-Atherosclerotic Therapies ... 259 Peter D. Reaven and Wulf Palinski
xii Contents
PARTII. CLINICAL
A. RISK FACTORS
13 The Metabolic Syndrome and Vascular Disease ... 281 S. J. Creely, Aresh J. Anwar, and Sudhesh Kumar
14 Diabetes and Hypertension ... 307 Samy I. McFarlane, Amal F. Farag, David Gardner,
and James R. Sowers
15 Diabetes and Dyslipidemia ... 329 Asha Thomas-Geevarghese, Catherine Tuck,
and Henry N. Ginsberg B. MICROCIRCULATION
16 Diabetic Retinopathy ... 349 Lloyd Paul Aiello and Jerry Cavallerano
17 Diabetic Nephropathy ... 367 Richard J. Solomon and Bijan Roshan
18 Diabetic Neuropathy ... 381 Rayaz A. Malik and Aristidis Veves
19 Microcirculation of the Diabetic Foot ... 403 Chantel Hile and Aristidis Veves
C. CARDIOVASCULAR SYSTEM: PERIPHERAL VASCULAR SYSTEM
20 Epidemiology of Peripheral Vascular Disease ... 419 Stephanie G. Wheeler, Nicholas L. Smith, and Edward J. Boyko
21 Noninvasive Methods to Assess Vascular Function
and Pathophysiology ... 431 Peter G. Danias and Rola Saouaf
22 Peripheral Vascular Disease in Patients With Diabetes Mellitus ... 451 Bernadette Aulivola, Allen D. Hamdan, and Frank W. LoGerfo
23 Therapeutic Interventions to Improve Endothelial Function
in Diabetes ... 465 Lalita Khaodhiar and Aristidis Veves
D. CARDIOVASCULAR SYSTEM: CARDIAC
24 Preoperative Assessment and Perioperative Management
of the Surgical Patient With Diabetes Mellitus ... 487 Alanna Coolong and Mylan C. Cohen
25 Diabetes and Percutaneous Interventional Therapy ... 519 David P. Lorenz, Joseph P. Carrozza, and Lawrence Garcia
26 Cardiac Surgery and Diabetes Mellitus ... 543 Tanveer A. Khan, Pierre Voisine, and Frank W. Sellke
27 Heart Failure and Cardiac Dysfunction in Diabetes ... 555 Lawrence H. Young, Raymond R. Russell, III,
and Deborah Chyun
28 Diabetes Mellitus and Heart Disease ... 579 Michael T. Johnstone and George P. Kinzfogl
Index ... 629
Contents xiii
C
ONTRIBUTORSLLOYD PAUL AIELLO,MD,PhD, Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, Boston, MA
ARESH J. ANWAR,MD,MRCP, Division of Clinical Sciences, Warwick Medical School, University of Warwick and University Hospital of Coventry and Warwickshire, Coventry, UK
BERNADETTE AULIVOLA,MD, Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA EDWARD J. BOYKO,MD,MPH, Department of Medicine, University of Washington
School of Medicine; Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA
JOSEPH P. CARROZZA,MD, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
JERRY CAVALLERANO,OD,PhD, Joslin Diabetes Center, Harvard Medical School, Boston, MA
DEBORAH CHYUN,RN,PhD, Adult Advanced Practice Nursing Speciality, Yale University School of Nursing, New Haven, CT
MYLAN C. COHEN,MD,MPH, Maine Cardiology Associates, Maine Medical Center, Portland, ME; Department of Medicine, University of Vermont College of Medicine, Burlington, VT
ALANNA COOLONG,MD, Division of Cardiology, Maine Medical Center, Portland, ME S. J. CREELY,MD, Division of Clinical Sciences, Warwick Medical School, University of Warwick and University Hospital of Coventry and Warwickshire, Coventry, UK PETER G. DANIAS,MD,PhD, Department of Medicine, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA; Hygeia Hospital, Maroussi, Greece PANAYIOTIS ECONOMIDES,MD, Research Division, Joslin Diabetes Center, Harvard
Medical School, Boston, MA
AMAL F. FARAG,MD, Division of Endocrinology, New York Harbor Veterans Administration Center, Brooklyn, NY
EDWARD P. FEENER,PhD, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA
LAWRENCE GARCIA,MD, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
DAVID GARDNER,MD, Division of Endocrinology, University of Missouri, Columbia, MO ALINA GAVRILA,MD, Division of Endocrinology and Metabolism, Department
of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA ELI GELFAND,MD, Cardiovascular Division, Department of Medicine, Beth Israel
Deaconess Medical Center, Boston, MA
HENRY N. GINSBERG,MD, College of Physicians and Surgeons of Columbia University, New York, NY
ALLEN D. HAMDAN,MD, Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
xv
ZHIHENG HE,MD,PhD, Research Division, Joslin Diabetes Center, Department of Ophthalmology, Harvard Medical School, Boston, MA
CHANTEL HILE,MD, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
MICHAEL T. JOHNSTONE,MD,CM,FRCP(C), Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
TANVEER A. KHAN,MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Department of Medicine and Surgery, Harvard Medical School, Boston, MA
LALITA KHAODHIAR,MD, Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
GEORGE L. KING,MD, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA
GEORGEP. KINZFOGL,MD, Staff Cardiologist, Health Center of Metrowest, Framingham, MA SUDHESH KUMAR,MD,FRCP, Division of Clinical Sciences, Warwick Medical School,
University of Warwick and University Hospital of Coventry and Warwickshire, Coventry, UK
FRANK W. LOGERFO,MD, Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA MARIA F. LOPES-VIRELLA,MD,PhD, Division of Endocrinology, Diabetes and Medical
Genetics, Department of Medicine, Medical University of South Carolina;
Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC DAVID P. LORENZ,MD, Department of Medicine, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA
RAYAZ A. MALIK,MB ChB,PhD, Department of Medicine, Manchester Royal Infirmary, Manchester, UK
CHRISTOS S. MANTZOROS,MD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA
SAMY I. MCFARLANE,MD,MPH, Department of Medicine, State University of New York Health Science Center at Brooklyn Kings, County Hospital Center, Brooklyn, NY KEIKO NARUSE,MD,PhD, Research Division, Joslin Diabetes Center, Harvard Medical
School, Boston, MA
PÁL PACHER,MD,PhD, Inotek Pharmaceuticals, Beverly, MA; Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD; Institute of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
WULF PALINSKI,MD, Department of Medicine, University of California, San Diego, School of Medicine, San Diego, CA
MELPOMENI PEPPA,MD, Department of Geriatrics, Mount Sinai School of Medicine, New York, NY
JORGE PLUTZKY,MD, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
PETER D. REAVEN,MD, Department of Medicine, Carl T. Hayden VA Medical Center, Phoenix, AZ
BIJAN ROSHAN,MD, Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
xvi Contributors
RAYMOND R. RUSSELL, III, MD,PhD, Department of Internal Medicine (Cardiovascular Medicine), Yale University School of Medicine, New Haven, CT
ROLA SAOUAF,MD, Department of Radiology, New York-Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY
DAVID J. SCHNEIDER,MD, Department of Medicine, The University of Vermont College of Medicine, Burlington, VT
FRANK W. SELLKE,MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
SUKETU SHAH,MD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
NICHOLAS L. SMITH,PhD,MPH, Investigator, Cardiovascular Health Research Unit, University of Washington School of Medicine, Seattle, WA
BURTON E. SOBEL,MD, Department of Medicine, The University of Vermont College of Medicine, Burlington, VT
RICHARD J. SOLOMON,MD, Department of Medicine, The University of Vermont College of Medicine, Burlington, VT
JAMES R. SOWERS,MD,FACP, Department of Cardiovascular Medicine, University of Missouri, Columbia, MO
HELMUT O. STEINBERG,MD, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, IN
CSABA SZABÓ,MD,PhD, Inotek Pharmaceuticals, Beverly, MA; Department of Human Physiology and Experimental Research, Semmelweis University, Budapest, Hungary ASHA THOMAS-GEEVARGHESE,MD, Department of Medicine, College of Physicians
and Surgeons of Columbia University, New York, NY; Medstar Research Institute, Washington, DC
AGATHOCLES TSATSOULIS,MD,PhD,FRCP, Division of Endocrinology, Department of Medicine, University of Ioannina Medical School, Ioannina, Greece
CATHERINE TUCK,MD, (Deceased) formerly Assistant Professor of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY
JAIME URIBARRI,MD, Division of Nephrology, Mount Sinai School of Medicine, New York, NY
DOUGLAS E. VAUGHAN,MD, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Veterans Administration Medical Center, Nashville, TN
ARISTIDIS VEVES,MD,DSc, Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center; Department of Surgery, Harvard Medical School, Boston, MA
GABRIEL VIRELLA,MD,PhD, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC
HELEN VLASSARA,MD, Department of Geriatrics, Mount Sinai School of Medicine, New York, NY
PIERRE VOISINE,MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
STEPHANIE G. WHEELER,MD,MPH, Department of Medicine, University of Washington School of Medicine and VA Puget Sound Health Care System, Seattle, WA LAWRENCE H. YOUNG,MD, Department of Internal Medicine (Cardiovascular
Medicine), Yale University School of Medicine, New Haven, CT
Contributors xvii
