Atlas of Atherosclerosis and Metabolic Syndrome wwwww Atlas of Atherosclerosis and Metabolic Syndrome Editor Prof. Dr. Scott M. Grundy University of Texas Southwestern Medical Center Department of Clinical Nutrition and Internal Medicine Harry Hines Blvd. 5323 75390 Dallas Texas USA Editor Dr. Scott M. Grundy University of Texas Southwestern Medical Center Department of Clinical Nutrition and Internal Medicine Harry Hines Blvd. 5323 75390 Dallas Texas USA [email protected] Fourth edition: Current Medicine LLC, 2005 Third edition: Current Medicine Inc, 2003 Second edition: Current Medicine Inc, 2000 First edition: Current Medicine Inc, 1996 ISBN 978-1-4419-5838-9 e-ISBN 978-1-4419-5839-6 DOI 10.1007/978-1-4419-5839-6 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2010938857 © Springer Science+Business Media, LLC 2011 All rights reserved. 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The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface The past two decades have seen an explosion of new infor- trials using these drugs has shown that LDL-lowering ther- mation on the causation, prevention, and treatment of ath- apy can cause marked reductions in risk for ASCVD events. erosclerotic cardiovascular disease (ASCVD). For many These drugs are combined with other pharmacologic ther- years, atherosclerosis was viewed as being a set of inert apies to control other risk factors, it is now possible to cut plaques on the surface of arteries that grow slowly in size risk for new ASCVD events by at least one half. and can eventually occlude their lumens. According to this Unfortunately, the benefits of antiatherogenic diets and view, when obstructions become severe enough blood flow drugs have been increasingly offset by a rise in obesity will be curtailed to the point that infarction of distal tissues prevalence in the general population. Obesity contributes will occur. This process in coronary arteries results in myo- importantly to the metabolic syndrome. This condition is cardial infarction, and in the brain, stroke. In the past characterized by a constellation of metabolic risk factors decade or so, however, a revolution in thinking has occurred for ASCVD; these include elevated triglycerides, reductions about the pathogenesis and fates of atherosclerotic plaques. in high-density lipoproteins (HDL), elevated blood pres- They are now considered to be active, inflammatory lesions. sure, higher glucose levels, a proinflammatory state, and a And myocardial infarctions and strokes are most likely to prothrombotic state. The presence of the metabolic syn- occur when plaques rupture or erode. These disruptions drome at least doubles the risk for ASCVD. One condition result in superimposed thrombi, which are responsible for that is closely associated with the metabolic syndrome is clinical syndromes (eg, myocardial infarction and stroke). type 2 diabetes. The obesity-driven increase in type 2 dia- Further, the severity of inflammation in plaques determines betes in the population has emerged as a major cause of which are stable and which are unstable; the latter being ASCVD in our society. One of the major challenges for the particularly likely to undergo rupture. Much has been prevention in cardiovascular disease is to reduce obesity learned about the inflammatory process in arterial walls and to develop new strategies for management of the meta- and about how cardiovascular risk factors produce arterial bolic syndrome. Its management represents another major inflammation. medical challenge. The primary approach for treatment of Central in atherogenesis is lipid accumulation, which is metabolic syndrome is weight reduction combined with the prime trigger for arterial inflammation. Low density increased physical activity. In higher risk patients, treat- lipoproteins (LDL), are especially proinflammatory and ment of individual risk factors with drugs may be hence are proatherogenic. Much has been learned about the necessary. metabolism of lipoproteins over the past five decades but This volume tells the story of atherosclerotic disease only more recently has this knowledge been put to use for from arterial wall biology, through risk factor contribution, reducing atherosclerosis and preventing ASCVD. The gen- to clinical management. It is prepared by leading investiga- eral public has been gradually lowering serum LDL levels tors in each of these fields. The presentation is reader through dietary change. This undoubtedly has produced friendly, with presentation of information in an easy-to- some reduction in ASCVD. But in the past 15 years, new read slide format. The authors believe that this book will drugs have become available that effectively and safely provide a valuable resource for better understanding the reduce levels of atherogenic lipoproteins. A series of clinical scope of ASCVD. Prof. Dr. Scott M. Grundy Texas, USA v wwwww Contributors Nicola Abate, MD David Frankel, MD James B. Meigs, MD, MPH Professor and Chief Division of Fellow, Department of Medicine, Assistant Professor of Medicine, Assistant Endocrinology Charles Sprague MD Division of Cardiovascular Medicine, Physician, General Medicine Division, Distinguished Professor in Internal University of Pennsylvania, Philadelphia, Harvard Medical School, Massachusetts Medicine, The University of Texas Medical Pennsylvania General Hospital, Boston, Massachusetts Branch, Galveston, Texas Scott M. Grundy, MD, PhD Viviane Rocha, MD H. Bryan Brewer, Jr. MD Distinguished Chair in Human Nutrition, Research Fellow, Cardiovascular Division, Director, Washington Cardiovascular Professor, Internal Medicine�Nutrition and Department of Medicine, Brigham and Associates, Senior Research Consultant, Metabolic Diseases, University of Texas Women’s Hospital, Boston, Massachusetts Lipoprotein and Atherosclerosis Research, Southwestern Medical Center at Dallas, Cardiovascular Research Institute, MedStar Dallas, Texas Jonathan Shaw, MD, MRCP (UK), Research Institute, Washington Hospital FRACP Center, Washington, DC Craig A. Johnston, PhD Associate Professor, Epidemiology and Instructor, Department of Pediatrics- Clinical Diabetes, Baker IDI Heart and W. Virgil Brown, MD Nutrition, Children’s Nutrition Research Diabetes Institute, Melbourne, Victoria, Charles Howard Candler Professor of Center, Baylor College of Medicine, Houston, Australia Internal Medicine, Department of Medicine, Texas Division of Endocrinology, Metabolism, and Neil J. Stone, MD Lipids, Medical Specialty Service Line, Ngoc-Anh Le, PhD Professor of Medicine, Medical Director, Atlanta Veterans Affairs Medical Center, Department of Cardiology, Center for Emory University, Atlanta, Georgia Associate Professor of Medicine, Vascular Disease, Feinberg School of Department of Medicine, Division Medicine, Northwestern University, Bluhm Adrian Cameron, PhD, MPH of Endocrinology, Metabolism, and Lipids, Cardiovascular Institute, Northwestern Postdoctoral Research Fellow, Epidemiology Emory University, Research Scientist, Atlanta Memorial Hospital, Chicago, Illinois and Clinical Diabetes, Baker IDI Heart and Veterans Affairs Medical Center, Atlanta, Diabetes Institute, Melbourne, Victoria, Georgia Nanette K. Wenger, MD Australia Professor of Medicine, Chief of Cardiology, Peter Libby, MD Division of Cardiology, Emory University Manisha Chandalia, MD Mallinckrodt Professor of Medicine, Chief, School of Medicine, Grady Memorial Associate Professor of Medicine, The Cardiovascular Division, Harvard Medical Hospital, Atlanta, Georgia University of Texas Medical Branch, School, Brigham and Women’s Hospital, Galveston, Texas Boston, Massachusetts Peter W. F. Wilson, MD Professor of Medicine, Professor of Public Niels Engberding, MD Alice H. Lichtenstein, DSc Health, Director of Epidemiology and Professor of Medicine, Division of Stanley N. Gershoff Professor of Nutrition Genomic Medicine, Cardiology Division, Cardiology, Emory University School of Science and Policy Gerald J. and Dorothy R. Rollins School of Public Health Emory Medicine, Chief of Cardiology, Grady Friedman Society of Nutrition Science and University, Atlanta Veterans Affairs Medical Memorial Hospital, Atlanta, Georgia Policy Professor, Director and Senior Center, Atlanta, GA Scientist, Department of Medicine, John P. Foreyt, PhD Cardiovascular Nutrition Laboratory, Tufts Professor, Director, Department of Medicine, University, Jean Mayer USDA Human Behavioral Medicine Research Center, Baylor Nutrition Research Center on Aging at Tufts College of Medicine, Houston, Texas University, Boston, Massachusetts vii wwwww Contents Chapter 1 The Metabolic Syndrome.......................................................... 1 Scott M. Grundy Chapter 2 Epidemiology of the Metabolic Syndrome and Risk for Cardiovascular Disease and Diabetes..................................................................... 27 Adrian Cameron and Jonathan Shaw Chapter 3 The Metabolic Syndrome and Atherogenesis........................................ 45 Viviane Z. Rocha and Peter Libby Chapter 4 Triglyceride-Rich Lipoproteins .................................................... 59 Ngoc-Anh Le and W. Virgil Brown Chapter 5 High-Density Lipoprotein Metabolism ............................................. 93 H. Bryan Brewer Jr Chapter 6 Newer Coronary Risk Factors...................................................... 113 Peter W. F. Wilson Chapter 7 Dietary Effects on Cardiovascular Risk Factors ..................................... 141 Alice H. Lichtenstein Chapter 8 Strategies for Treating Abnormal Lipid Profiles with Drugs .......................... 163 Neil J. Stone Chapter 9 Ethnic Differences in the Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Nicola Abate and Manisha Chandalia Chapter 10 Obesity Management ............................................................. 207 Craig A. Johnston and John P. Foreyt Chapter 11 Diabetes Mellitus and Cardiovascular Disease ...................................... 227 David S. Frankel, Peter W. F. Wilson, and James B. Meigs Chapter 12 Gender Differences in Coronary Risk Factors and Risk Interventions ................. 253 Niels Engberding and Nanette K. Wenger Index............................................................................ 301 ix