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Atherosclerosis, Large Arteries and Cardiovascular Risk

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Advances in Cardiology
Vol. 44

Series Editor

Jeffrey S. Borer

New York, N.Y.

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Atherosclerosis,
Large Arteries and
Cardiovascular Risk
Volume Editors

Michel E. Safar Paris

Edward D. Frohlich New Orleans, La.

63 figures, 1 in color, and 29 tables, 2007

Basel Freiburg Paris London New York

Bangalore Bangkok Singapore Tokyo Sydney

Advances in Cardiology

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Prof. Dr. Michel E. Safar

Prof. Dr. Edward D. Frohlich

Hpital Htel-Dieu
Centre de Diagnostic
1 place du Parvis Notre-Dame
F75181 Paris Cedex (France)

Ochsner Clinic Foundation

1514 Jefferson Highway
New Orleans, LA 70121 (USA)

Library of Congress Cataloging-in-Publication Data

Atherosclerosis, large arteries, and cardiovascular risk / volume editors,
Michel E. Safar, Edward D. Frohlich.
p. ; cm. (Advances in cardiology ; v. 44)
Includes bibliographical references and index.
ISBN-13: 978-3-8055-8176-9 (hard cover : alk. paper)
1. AtherosclerosisPathophysiology. 2. ArteriosclerosisPathophysiology.
3. Coronary heart diseaseEtiology. I. Safar, Michel. II. Frohlich, Edward D., 1931- .
III. Series.
[DNLM: 1. Atherosclerosisphysiopathology. 2. Arteriesphysiopathology.
3. Atherosclerosiscomplications. 4. Cardiovascular Diseasesetiology. 5. Risk Factors.
W1 AD53C v.44 2007 / WG 550 A8694 2007]
RC692.A6748 2007
2006030607
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and
Index Medicus.
Disclaimer. The statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the
book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness,
quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and
dosage set forth in this text are in accord with current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information
relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any
change in indications and dosage and for added warnings and precautions. This is particularly important when
the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or
utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying,
or by any information storage and retrieval system, without permission in writing from the publisher.
Copyright 2007 by S. Karger AG, P.O. Box, CH4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISSN 00652326
ISBN-10: 3805581769
ISBN-13: 9783805581769

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Contents

VII Preface
Section I Pathophysiology
1 Arterial Stiffness: A Simplified Overview in Vascular Medicine
Safar, M.E. (Paris)
19 Aging and Arterial Structure-Function Relations
Izzo, J.L. Jr. (Buffalo, N.Y.); Mitchell G.F. (Waltham, Mass.)
35 Local Elasticity Imaging of Vulnerable Atherosclerotic Coronary Plaques
Baldewsing, R.A.; Schaar, J.A.; Mastik, F. (Rotterdam);
van der Steen, A.F.W. (Rotterdam/Utrecht)
62 Endothelial Function, Mechanical Stress and Atherosclerosis
Hayoz, D.; Mazzolai L. (Lausanne)
76 Arterial Stiffness and Extracellular Matrix
Dez, J. (Pamplona)
96 Animal Models of Arterial Stiffness
Atkinson, J. (Nancy)
Section II Arterial Stiffness, Atherosclerosis and End-Organ Damage
117 Blood Pressure, Large Arteries and Atherosclerosis
Frohlich, E.D.; Susic, D. (New Orleans, La.)
125 Arterial Stiffness and Coronary Ischemic Disease
Kingwell, B.A.; Ahimastos, A.A. (Melbourne)
139 Central Pulse Pressure and Atherosclerotic Alterations of Coronary
Arteries
Danchin, N. (Paris); Mourad, J.-J. (Bobigny)
150 Does Brachial Pulse Pressure Predict Coronary Events?
Verdecchia, P.; Angeli, F. (Perugia)

160 Does Arterial Stiffness Predict Atherosclerotic Coronary Events?

McEniery, C.M. (Cambridge); Cockcroft, J.R. (Cardiff)
173 Carotid Atherosclerosis, Arterial Stiffness and Stroke Events
Agabiti-Rosei, E.; Muiesan, M.L. (Brescia)
187 Atherosclerosis versus Arterial Stiffness in Advanced Renal Failure
Guerin, A.; Pannier, B.; London, G. (Fleury Mrogis)
199 Arterial Stiffness and Peripheral Arterial Disease
Safar, M.E. (Paris)
Section III Arterial Stiffness, Atherosclerosis and Cardiovascular Risk Factors
212 Cardiovascular Risk Factors, Atherosclerosis and Pulse Pressure
Amar, J.; Chamontin, B. (Toulouse)
223 Pulse Pressure and Inflammatory Process in Atherosclerosis
Abramson, J.L.; Vaccarino, V. (Atlanta, Ga.)
234 Calcifications, Arterial Stiffness and Atherosclerosis
Mackey, R.H.; Venkitachalam, L.; Sutton-Tyrrell, K. (Pittsburgh, Pa.)
245 Diabetes and Arterial Stiffening
Winer, N. (New York, N.Y.); Sowers, J.R. (Columbia, Mo.)
252 Insulin Resistance, Arterial Stiffness and Wave Reflection
Yki-Jrvinen, H.; Westerbacka, J. (Helsinki)
261 Cholesterol, Lipids and Arterial Stiffness
Wilkinson, I. (Cambridge); Cockcroft, J.R. (Cardiff)
278 Homocysteine and Large Arteries
van Guldener, C. (Breda); Stehouwer, C.D.A. (Maastricht)
Section IV Therapeutic Aspects
302 Nitrates, Arterial Function, Wave Reflections and Coronary Heart Disease
Smulyan, H. (Syracuse, N.Y.)
315 Modulation of Atherosclerosis, Blood Pressure and Arterial Elasticity
by Statins
Sinha, A.K.; Mehta, J.L. (Little Rock, Ark.)
331 Atherosclerosis, Arterial Stiffness and Antihypertensive Drug Therapy
Safar, M.E. (Paris); Smulyan, H. (Syracuse, N.Y.)
352 Author Index
353 Subject Index

Contents

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Preface

In recent years, our fundamental knowledge of atherosclerosis in the human being has dramatically increased, not only from a better understanding
of the pathophysiological information, but also from the clinical use of new
hypolipidemic agents which are so very different from the traditional therapeutic mechanisms directed toward atherosclerotic disease. This advance was
exceedingly important for all clinical investigators since their clinical approach to atherosclerotic disease has changed, particularly regarding its links
with hypertension and the aging process.
Moreover, as a consequence of new epidemiological findings, we have divided the well-established vascular diseases into two pedagogic categories:
those related to cardiovascular risk factors (hypertension, diabetes mellitus,
dyslipidemia, obesity and smoking) and those related to specific clinical events
affecting the target organ circulations (i.e., brain, kidney, heart, and lower
limbs). Furthermore, because of increased longevity in recent years, a dissociation of atherosclerosis from the effects of aging per se has been a major effort
in presenting the concept of this textbook. Another important point needed to
be clarified: in understanding the different clinical and hemodynamic features
of atherosclerosis, it was important to present a current means of evaluating
cardiovascular risk as well as a practical rationale for developing a therapeutic
strategy.
Finally, in arriving at a dissociation and understanding of the mechanisms of hypertensive disease and of the aging process, the structural and
functional changes of the vessels of each must be recognized as clearly as possible with respect to how they involve the totality of the arterial and arteriolar

VII

system. Thus, it is necessary to comprehend both the aging phenomenon and

the pathophysiology of hypertension and their respective global impacts on
arterial stiffness, especially involving the aorta and its major large arterial
branches. In this regard, the clinical aspects of arterial stiffness have been
widely developed in hypertensive subjects over the last 10 years. In contrast, in
patients with atherosclerosis, the distribution of arterial rigidity on large vessels is much more patchy and predominates in certain arteries for example
the coronary arteries and at the level of the arterial bifurcations. In these vessels, non-fibrous and non-calcified plaques do not necessarily contribute to
increased vessel stiffness. Therefore, the problem of arterial rigidity in atherosclerosis is more difficult to resolve than in hypertension. For these reasons,
the principal purpose of this book was to respond to the following questions:
In which conditions does the atherosclerosis process contribute to the development of vascular stiffness and to vascular calcifications since both of these factors independently participate in determining cardiovascular risk and, possibly, in modifying therapeutic strategy?
This book is composed of four sections. First, the definition and measurement of arterial stiffness are described with respect to the pathophysiological
aspects of atherosclerosis. Second, the mechanisms underlying arterial stiffness are described successively in the major territories involved with atherosclerosis, particularly the coronary arteries. Third, arterial stiffness is discussed with respect to its relation with other cardiovascular factors such as
diabetes mellitus or hyperlipidemia. Finally, in the fourth section the therapeutic means of approaching arterial stiffness are analyzed in detail. We hope
this approach to the effects of arterial stiffness involving hypertension, atherosclerosis, and aging is now better understood and that it will, in turn, result in
a more clearly developed concept for therapy in the future.
Michel E. Safar, Paris
Edward D. Frohlich, New Orleans, La.

Preface

VIII