Atherosclerosis V ATHERO• SCLEROSIS V

Proceedings of the Fifth International Symposium

Edited by Antonio M. Gotto, Jr. Louis C. Smith Barbara Allen

With 250 illustrations

Springer-Verlag New York Heidelberg Berlin Proceedings of the Fifth International Symposium on Atherosclerosis

Held in Houston, November 6-9, 1979

Sponsored by Baylor College of Medicine and The Methodist Hospital, Houston, Texas

No part of this book may be translated or reproduced in any form without written permission from Springer-Verlag.

The use of general descriptive names, trade names, trademarks, etc. in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone.

9 8 7 654 3 2 1 ISBN-13: 978-1-4612-6073-8 e-ISBN-13: 978-1-4612-6071-4 DOl: 10.1007/978-1-4612-6071-4 INTERNATIONAL PROGRAM COMMITTEE

Jean-Louis Beaumont David Kritchevsky Henry Buchwald K.T. Lee Lars A. Carlson Kare R. Norum William E. Connor Michael F. Oliver Alan J. Day Rodolfo Paoletti Frederick H. Epstein Gotthard Schettler Yuichiro Goto Gunther Schlierf Antonio M. Gotto, Jr. Yechezkiel Stein M. Daria Haust Daniel Steinberg William L. Holmes Jack P. Strong Anatoli N. Klimov

ORGANIZING COMMITTEE

Chairman: Antonio M. Gotto, Jr. Co-Chairman: Yuichiro Goto General Secretary: Louis C. Smith Symposium Coordinator: Jean King Scientific Editor: Barbara Allen

ACKNOWLEDGEMENTS

We gratefully acknowledge the following individuals, institutions, organizations and companies whose generosity and support made this meeting possible.

William L. Holmes Abbott Laboratories Lars A. Carlson American Cyanamid Company Yuichiro Goto Ayerst M. Daria Haust Best Foods David Kritchevsky Burroughs Wellcome Company Henry C. McGill Ciba Geigy Corporation Paul J. Nestel Dow Chemical Company, USA Michael F. Oliver Hoffman-LaRoche, Inc. Rodolfo Paoletti Eli Lilly and Company Gotthard Schettler McNeil Laboratories Yechezkiel Stein Mead Johnson Pharmaceutical Division Daniel Steinberg Merck Sharp and Dohme Research Robert W. Wissler Laboratories Baylor College of Medicine Miles Laboratories, Inc. The Methodist Hospital Norwich Eaton Council on Arteriosclerosis of the Ortho Pharmaceutical Corporation American Heart Association The Proctor and Gamble Corporation

v William H. Rorer, Inc. Standard Brands, Inc. Sandoz, Inc. Sun Company Schering Corporation Syntex Research G.D. Searle and Company The Upjohn Company Smith, Kline and French Laboratories Wyeth Laboratories, Inc.

vi PREFACE

The objective of the program committee of the Fifth International Symposium on Atherosclerosis was to bring together experts in many disciplines to broaden the scope of the attack on this disease and to foster interaction. Our hope was that such interaction would accelerate the eradication of the disease. The symposium achieved that objective and con• tinued the tradition of the previous symposia in providing a forum for summaries of recent research developments in the study, treatment and prevention of atherosclerosis. The leading authorities and researchers in this field and in the related areas of interest have presented the newest information, concepts and ideas that have evolved in the past three years since the previous meeting in Tokyo. The most promising fields for future investigation are clearly identified, as are the nature of the controversies that persist in some highly important aspects of treatment of this disease. The appearance of these proceedings so soon after the meeting will greatly enhance the impact of the symposium on current research in atherosclerosis. The program committee is particularly indebted to the excellent response of the inves• tigators for their willingness to participate in the symposium and for their successful efforts in bringing high quality to their presentations. Their cooperation in the expeditious delivery of manuscripts for this volume has been particularly gratifying. The efforts of Ms. Barbara Allen in preparing this volume bear special note. The Chairman and the General Secretary gratefully acknowledge their debt of gratitude to Ms. Jean King, whose extraordinary skill and effort provided a pleasant, superbly organized and well-managed context for this sym• posium.

Antonio M. Gotto, Jr. Chairman

Louis C. Smith General Secretary

November 23, 1979 Houston, Texas

vii INTRODUCTION

Baylor College of Medicine and The Methodist Hospital hosted the Fifth International Symposium on Atherosclerosis in Houston, Texas, November 6-9, 1979. The honorary co-sponsors of the Symposium were Mrs. Mary Lasker of New York and Princesse Lilian of Belgium, two distinguished supporters of biomedical research. Because of their long interest in programs for the treatment and prevention of cardiovascular disease, the Fifth Interna• tional Symposium conferred distinguished service awards on Mrs. Lasker and Princesse Lilian. Distinguished service awards were also given to Dr. Michael DeBakey, President and Chancellor of Baylor College of Medicine, for his contributions to the surgical treatment of atherosclerosis; to Mr. Ted Bowen, the President of The Methodist Hospital, for his vision. foresight. and administrative leadership in providing the facilities for a comprehensive car• diovascular center; and to Professors Gotthard Schettler of Heidelberg and Yuichiro Goto of Tokyo for their long and dedicated work in the field of atherosclerosis. At the meeting. Professor Schettler announced the establishment of a new organization called the Interna• tional Atherosclerosis Society. The Fifth International Symposium on Atherosclerosis was the first to be held under the auspices of the new International Atherosclerosis Society. The Symposium demonstrated the dynamic growth of the field, the progress that has been made since the previous symposium in Tokyo, and the fact that atherosclerosis has become a remarkably interdisciplinary activity. One of the most gratifying aspects of the Symposium was the degree of interchange between basic and clinical scientists, epidemiologists, biochemists, nutritionists, cardiologists and cardiovascular surgeons. The opening session of the Houston Symposium honored Dr. DeBakey's contributions to the surgical treatment of atherosclerosis. As it presents to the surgeon atherosclerosis may follow a number of different patterns. One is the primary distribution of the lesions, for example, whether the coronary, the carotid or the peripheral arteries are involved, or a combination thereof. Another characteristic feature is whether the disease involves primarily distal or proximal blockage. A third characteristic relates to the rate of progression of the disease: rapid, slow or intermediate. It has not yet been possible to establish correlations between several of the patterns and any known constellation of risk factors. Another type of pattern, of which the frequency is unknown, are those individuals who may have coronary artery spasm. usually superimposed on underlying coronary artery obstruction, but in some instances without significant underlying coronary atherosclerotic lesions. A workshop was devoted to the topic of coronary bypass surgery. Both the cardiologists and cardiovascular surgeons exhibited a considerable degree of enthusiasm for the procedure. There was even some note of optimism that the procedure may prolong life. Regardless of this last point, which remains a controversial one, the overall consensus of the participants in the workshop was one of enthusiasm for coronary artery bypass surgery as a treatment for obstructive disease of the coronary arteries. The relatively new procedure of coronary angio• plasty may also prove to be beneficial to patients with certain types of coronary artery obstruction. This subject was to be extensively discussed at the annual meeting of the American Heart Association and one under intensive investigation. The question of treatment of hyperlipidemia continues to be spiced with controversy. A

ix number of different methods of reducing blood lipids discussed at the Symposium included diet, the subject of the second plenary session, drugs, ileal bypass surgery, portacaval shunt and plasma exchange procedures. Some preliminary evidence from human studies suggests that atherosclerosis may be reversible in man. The majority of individuals in intervention trials for relatively short periods of time will probably show failure of progression rather than clear-cut evidence of regression. What is needed is a way of achieving more than a marginal reduction of cholesterol or low density lipoproteins (LDL). For example, if it were possible to lower the cholesterol to less than about 150 mg/dl with a concomitant reduction in LDL, then extensive long-term intervention trials might not be required in order to show a clear-cut effect on morbidity and mortality. Some promising new drugs described at the Symposium include a new inhibitor of HMO CoA reductase. A distinguished group of scientists could not agree on what information should be conveyed to the general public about diet. The fields of nutrition, platelet biochemistry, thrombosis prostaglandin chemistry, and cardiovascular disease are merging, as was illus• trated by the plenary sessions on diet and on the vessel wall in which prostaglandin metabo• lism was discussed. In the platelet membranes from the Eskimo, an increased proportion of phospholipids containing unsaturated C-20:5 eicosopentanoic acid has been found. This most likely occurs as a consequence of ingesting the preformed fatty acids from fish in the Eskimo's diet. The Eskimo has been found to have a prolonged bleeding time. Several reviews claim that the Eskimo has a decreased incidence of coronary artery disease. Firm evidence for this latter point appears to be lacking, and it should be more intensively examined by epidemiologic studies. There is no evidence that consuming larger amounts of the C-20:3 fatty acid homo-y-linolenic acid would increase the arachidonic acid content of platelets since administration of lipid emulsions containing homo-linolenic acid results in a replacement of arachidonic acid by the homo-linolenic acid. Thus, the role of polyunsatu• rated fats continues to be a controversial one. Depending upon the polyunsaturated fatty acid composition of the diet, the cholesterol and LDL concentrations may be lowered and bleed• ing time may be prolonged. It seems likely that the fluidity of the platelet and other cellular membranes may be altered by the specific fatty acid composition and this in tum may affect associated membrane properties. One of the most encouraging reports at the meeting was that of a positive beneficial effect upon morbidity and mortality from treatment of mild hypertension in Australia. There continues to be much less controversy associated with efficacy of the treatment of hyperten• sion than that of hyperlipidemia. Among the information concerning hypertension presented at the meeting was the report of a possible new marker for essential hypertension, the measurement of an abnormality in the mechanism of potassium transport across the erythro• cyte. The use of drugs to affect the renin angiotensin axis also holds promise as providing new avenues for the treatment of hypertension. The importance of cell biology in atherosclerosis was again emphasized by the presenta• tion of important fundamental work at plenary sessions and at the workshops and oral sessions. The roles of the platelet growth factor of collagen and of glycosaminoglycans were discussed along with a number of other important topics. The study of the arterial wall has focused on the crucial cellular elements, viz., the endothelium, the smooth muscle cell and macrophage. No longer is atherosclerosis viewed as a disease of degeneration but rather one of proliferation. The role of hyperlipidemia in the proliferation of the cellular elements of the arterial wall is an important subject but remains to be defined. A panel of expert epidemiologists, cardiologists and internists could not agree on an explanation for the declining death rate for cardiovascular disease in the United States, although there was agreement that such a decrease has occurred. The overall decline in the death rate for cardiovascular disease for the past 15 years has been approximately 30% as x compared to 17% for noncardiovascular disease. A number of potential contributing factors have been suggested, including more effective detection and treatment of hypertension, a decline in the consumption of tobacco, a decrease in the use of saturated fats with a concomi• tant increase in consumption of polyunsaturated or vegetable fats, an apparent decline in the concentration of serum cholesterol and a national enthusiasm for exercise. Other countries, particularly European ones, have not shown a decline in death rate, although favorable trends may now be occurring. Despite these encouraging results, cardiovascular disease remains the number one cause of death and disability in Western society, accounting for over one-half the deaths in the United States each year. Approximately one million die each year in the United States from cardiovascular disease, of which about two-thirds are from myocardial infarc• tions. Thus, there is an enormous challenge yet awaiting physicians and researchers in the field of atherosclerosis and the end of this problem is far from visible at the present. The results of the World Health Organization study on clofibrate have been reported since the last symposium. These results have been variously interpreted. For those who want to interpret the study in a favorable way, the group receiving clofibrate experienced a 20% lower rate of nonfatal myocardial infarctions, which accompanied a 10% reduction in the concentration of serum cholesterol. For those who wish to interpret the study in a different light, the group taking the clofibrate had a higher mortality as compared to the placebo control group. It is hoped that the results of the Multiple Risk Factor Intervention Trial in the United States and of the Lipid Research Clinics intervention with cholestyramine will give a more clear-cut resolution of the lipid hypothesis. Regardless of the difficulties in proving or disproving the lipid hypothesis, interest in hyperlipidemia has lead to an explosion of research and knowledge concerning the structure and metabolism of plasma lipoproteins. This subject was extensively discussed in plenary sessions, workshops and in the oral sessions of the Symposium. An awareness of the complexity of the plasma lipoproteins has developed as more knowledge has evolved. Sub• classes and subgroups have been identified, some of which may have important metabolic implications. For example, do HDb and HDL3 differ in their ability to protect against atherosclerosis? A causal relationship between concentrations of HDL and coronary artery disease has not been established, although a strong negative correlation exists. Different subgroups of LDL may exist due to differences in carbohydrate composition or other chemi• cal properties. Work presented at the Symposium showed that some patients treated with drugs such as clofibrate responded with a reduction in LDL, while others exhibited an increase. Such findings illustrate the importance of performing careful metabolic studies of lipoprotein subclasses and apoproteins. Knowledge from such studies may form the basis of clinical tests that can be applied to patients and that can provide a more precise indication of who is likely to respond to a given hypolipidemic drug. Knowledge of the chemistry of the lipoproteins has greatly expanded with the identifica• tion of apoprotein groups extending from A through E. The primary amino acid sequence of five of the apoproteins is known. In addition to binding lipids, certain of the apoproteins have been shown to have other specific functions, for example, the activation of lecithin:choles• terol acyltransferase by apoA-I and apoC-I and lipoprotein lipase by apoC-II. ApoD, also called the thin-line peptide and apoA-III, may be identical to the cholesteryl ester transfer protein. Specific regions of the apoC-II have been identified which activate lipoprotein lipase and which are involved in lipid binding. Extensive evidence now exists to support the role of hydrophobic surfaces in the binding of apoproteins to phospholipids in the plasma lipopro• teins. The specific lipid binding sites are located in certain regions of the apoprotein called amphipathic helices. Often a great deal of valuable information concerning lipoprotein metabolism can be gained by the study of mutants, as was illustrated at the Symposium by work on abetalipop-

xi roteinemia, LCAT deficiency, hypobetalipoproteinemia, Tangier disease, a form of type I hyperlipoproteinemia which is due to the complete absence of apoC-II, and familial hyper• cholesterolemia. An outstanding example is the knowledge gained about LDL and choles• terol metabolism from the discovery of the LDL receptor; these investigators rested heavily on the use of patients with familial hypercholesterolemia, who either have a deficiency or a complete absence of the receptor. Evidence was presented at the Symposium to support the occurrence of the receptor in vivo employing chemically modified LDL. Just how much LDL under normal conditions goes through the non-LDL receptor pathway has not been estab• lished. While a deficiency of the LDL receptor can explain the elevation in levels of LDL, additional factors are required to explain why elevation of LDL produces atherosclerosis. If the receptor were working normally in the endothelial cell or smooth muscle cell, the system should be self-regulating. Evidence was reviewed that chemical modification of LDL can enhance its uptake by cells. Whether such mechanisms operate in vivo is not known. The purpose of my summary is not to list the most important or most significant work discussed at the Symposium, but rather to give a flavor of a few of the subjects discussed in order to indicate the interdisciplinary nature of the research and the great amount of progress that has been made since the last Symposium three years ago. The Symposium highlighted the hope that this progress will one day lead to the elucidation of the basic cause or causes of atherosclerosis and will point the way towards the development of solutions for the problem.

Antonio M. Gotto, Jr., M.D. Houston, Texas November 23, 1979

xii CONTENTS

Plenary Session: Cardiovascular Surgery (Co-Chairpersons: E.S. Crawford, D.C. Sabiston, Jf.) Atherosclerosis: Patterns and Rates of Progression (M.E. DeBakey) ...... 3 Surgery for Coronary Artery Disease (D.C. Sabiston, Jr.) ...... 8 Review of 30 Years of Surgery of the Heart and the Great Vessels (Ch. Dubost) ... 17 Mechanism of Progress. Page from the History of Cardiovascular Surgery (H.B. Shumacker, Jr.) ...... 26

Workshop: Coronary Bypass Surgery (Co-Chairpersons: M.E. DeBakey, J.W. Hurst) My Current Views Regarding Coronary Bypass Surgery (J.F. Goodwin) ...... 35 Results of Coronary Bypass: A Long-Term Perspective (G.M. Lawrie) ...... 40 Current Views Regarding Coronary Bypass Surgery (H.D. McIntosh) ...... 43 Comparison of Medical and Surgical Mortality in a High Risk Subset of Coronary Patients with Extreme Degrees of Exercise-Induced Ischemia (R.R. Miller, C.M. Pratt) ...... 47

Workshop: Epidemiology of Atherosclerotic Lesions (Co-Chairpersons: Y. Goto, J.P. Strong) Introduction to Epidemiology of Atherosclerotic Lesions (J.P. Strong, Y. Goto) ... 52 Epidemiology of Coronary Atherosclerosis: Postmortem vs Clinical Risk Factor Correla• tions. The Framingham Study (W.B. Kannel, P. Sorlie, F. Brand, W.P. Castelli, P.M. McNamara, G.J. Gherardi) ...... 54 Risk Factors for Coronary and Cerebral Atherosclerosis in the Oslo Study (L.A. Solberg, S.C. Enger, I. Hjermann, A. Helgeland, I. Holme, P. Leren, J.P. Strong) ... 57 Atherosclerosis and Its Risk Factors Among Hawaii Japanese (G.N. Stemmermann, G.G. Rhoads, T. Hayashi) ...... 63 Atherosclerosis, Smoking and Other Risk Factors (N.H. Sternby) ...... 67 See also Community Pathology of Atherosclerosis and Coronary Heart Disease in New Orleans: Relationship of Risk Factors to Atherosclerotic Lesions (J.P. Strong, W.D. Johnson, M.C. Oalmann, R.E. Tracy, W.P. Newman, Ill, W.A. Rock, G.T. Malcom, M.G. Kokatnur, V. Toca) ...... '" ...... 719

Workshop: Drug Treatment of Hyperlipidemia (Co-Chairpersons: D. Kritchevsky, R. Paoletti) Drug Treatment of Hyperlipidemias (D. Kritchevsky) ...... 71 Drug Treatment of Type II Hyperlipoproteinemia. Effects on Plasma Lipid and Lipopro- tein Levels (D.B. Hunninghake) ...... 74 xiii Synergism in Drug Treatment of Familial Hypercholesterolemia (J.P. Kane, P. Tun, M.J. Malloy, R.J. Havel) ...... 78 Effect of Plasma Lipoextraction and Infusion of Heterologous HDL on the Development of Experimental Atherosclerosis in Rabbits (A.N. Klimov, L. G. Petrova• Maslakova, G.G. Chetchinachvili, L.M. Tchichatarashvili, V.A. Nagomev, V.F. Tryufanov) ...... 83 New Drug Treatments in Hyperlipidaemia (A.G. Olsson) ...... 86 Apoprotein Changes Following Treatments with Hypolipidemic Drugs (C.R. Sirtori, G. Franceschini, M. Sirtori, G. Gianfranceschi, A. Poli) ...... 90

Workshop: The Arterial Wall-I (Co-Chairpersons: M.D. Haust, K.W. Walton)

Milieu and Function of Arterial Wall-The Clues to Unique Reactivity (M.D. Haust) 94 Atherogenetic Factors Intrinsic to the Artery Wall (K. W. Walton) ...... 98 Arterial Endothelium in the Initial Stages of Atherogenesis (A.L. Robertson, Jr.) .. 103 Ultrastructure of the Normal Arterial Endothelium and Intima (C.J. Schwartz, R.G. Gerrity, B.A. Sprague, M.R. Hagens, C.T. Reed, D.L. Guerrero) ...... 112 Biochemical Studies on Permeability and the Interaction Between Blood Constituents and Arterial Components in Atherosclerosis (E.B. Smith) ...... 121 Smooth Muscle Cells in Atherosclerosis (J.L. Titus, D.G. Weilbaecher) ...... 126 Mononuclear Phagocytes in Atherosclerosis (C.W.M. Adams, O.B. Bayliss-High) 130 Altered Permeability in Atherosclerosis-Morphological Evidence (S. U. Bjorkerud) 133 The Elastic Element in the Arterial Wall: Biosynthesis and Degradation (L. Robert) 136 Prostacyclin Production by Vascular Smooth Muscle and Endothelial Cells (H. Sin- zinger, K. Silberbauer, W. Auerswald) ...... 140

Workshop: Lipid, Apoprotein and Lipoprotein Origin and Synthesis (Co• Chairpersons: R.J. Havel, B. Lewis)

Lipid, Apoprotein and Lipoprotein Origin and Synthesis (B. Lewis, R.J. Havel) 144 Origin in Plasma of Low Density and High Density Lipoproteins (S. Eisenberg) 146 Biological and Biochemical Aspects of ML-236B (Compactin) and Monacolin K, Specific Competitive Inhibitors of 3-hydroxy-3-methylglutaryl Coenzyme A Re- ductase (A. Endo) ...... 152 Biosynthesis of Rat Apolipoprotein E (G.S. Getz, R. Hay, C. Reardon) ...... 156 Apoprotein Secretion from the Human Intestine (R.M. Glickman, P.H.R. Green) .. 160 Nascent VLDL and Nascent HDL from Liver (R.L. Hamilton) ...... 164 Synthesis and Secretion of Very Low Density Lipoprotein by Cultured Rat Hepatocytes (D.B. Weinstein, R.A. Davis, S.C. Engeihom, D. Steinberg) ...... 168

Workshop: Lipoprotein Structure (Co-Chairpersons: H.B. Brewer, Jr., W. Stoffel)

Topochemical Studies on Human High Density Lipoprotein (W. Stoffel) ...... 173 The Associating System of Small Subunits in ApoLDL (G. Camejo, L. Socorro) .. 176 Lipoprotein Structure and the Mechanism of Action of Lipoprotein Lipase (R.L. Jackson, M.R. Taskinen, N. Matsuoka, T.J. Fitzharris, J.A.K. Harmony, H.G. Muntz, E.K. Neely, A.D. Cardin, J.D. Johnson) ...... 180 Structure of High Density Lipoproteins (G.M. Kostner, P. Laggner, H. Hauser) 184 xiv Cholesteryl Ester-Rich Very Low Density Lipoproteins: Magnetic Resonance Studies (J.D. Morrisett, R.K. Stockton, R.D. Knapp) ...... 189

Plenary Session: Dietary Prevention of Coronary Heart Disease (Co-Chairpersons: R. I. Levy, G. Schettler)

Dietary Prevention of Coronary Artery Disease-A Policy Overview (R.1. Levy) 199 Dietary Prevention of Coronary Heart Disease (G. Schettler) ...... 209 Evaluation of the Evidence Relating National Dietary Patterns to Disease (E.H. Ahrens, Jr.) ...... 219 Diet-Lipid-Atherosclerosis Relationship: Epidemiological Evidence and Public Health Implications (H.W. Blackburn) ...... 220 Dietary Prevention of Coronary Heart Disease: The Role of Essential Fatty Acids (M.F. Oliver) ...... 235

Workshop: Hyperlipidemia: Prevalence and Inheritance (Co-Chairpersons: H.A. Eder, J. Slack)

Identification of Children Who Are Heterozygotes for Familial Hypercholesterolaemia (J. Slack, M. Preece, P. Giles) ...... 244 Lipoprotein and Apoprotein, Adipose Tissue and Hepatic Lipoprotein Lipase Levels in Patients with Familial Hyperchylomicronemia and Their Immediate Family Mem- bers (G. Crepaldi, R. Fellin, G. Baggio, J. Augustin, H. Greten) ...... 250 Studies of a Large French-Canadian Kindred with Two Forms of Hyperlipoproteinemia (1. Davignon, S. Lussier-Cacan, A. Gattereau, P.P. Moll, C. F. Sing) ...... 255 The Complex Genetics of Type III Hyperlipoproteinemia: Influence of Co-inherited Monogenic Hyperlipidemia upon the Phenotypic Expression of Apolipoprotein E3 Deficiency (W.R. Hazzard, G.R. Warnick, G. Utermann, J.J. Albers, B. Lewis) 260 Prevalence of Hyperlipoproteinemia in Selected North American Populations (B.M. Rifkind,L LaRosa, G. Heiss) ...... 264 Hypercholesterolemia Type IIa: Incidence of Secondary, of Familial and of Non- Familial Forms in Central Europe (N. Zollner, F. Spengel, G. Wolfram) ..... 268

Workshop: Risk Factors in Children (Co-Chairpersons: G.S. Berenson, M.J. Jesse)

Clues to Mechanisms of Cardiovascular Disease from an Epidemiologic Study of Children-The Bogalusa Heart Study (G.S. Berenson, S.R. Srinivasan, A.W. Voors, L.S. Webber) ...... 272 Cigarette Smoking: A Risk Factor for Atherosclerosis in Childhood? (M.J. Jesse) .. 278 Nutrient Intake, Lipids, and Lipoproteins in 6-19 Year Old Schoolchildren (LA. Morrison, R. Larsen, L. Glatfelter, D. Boggs, K. Burton, C. Smith, K.A. Kelly, M.J. Mellies, P. Khoury, c.J. Glueck...... 282 Pediatric Lipoprotein Metabolism and Atherosclerosis: A Prospectus (P.O. Kwiterovich, Jr.) ...... 286 Tracking of Coronary Risk Factors in Children: The Muscatine Study (R.M. Lauer, W.R. Clarke) ...... 294 Risk Factors in Children: Role of Hereditary Hyperlipoproteinemia (R.J. West, J.K. Lloyd) ...... 302 xv Workshop: Diet Treatment of Atherosclerosis (Co-Chairpersons: W.E. Connor, I.D. Frantz, Jr.)

Diet Treatment of Atherosclerosis (I.D. Frantz, Jr.) ...... 305 Body Weight, Dietary Fat, Hyperlipidemia, and Coronary Heart Disease (R.B. Blacket, P.J. Brennan, B. Leelarthaepin, C.A. McGilchrist, A.J. Palmer, J.M. Simpson, J.M. Woodhill) ...... 307 Effects of Dietary Fiber on Serum Lipids and Cholesterol Metabolism in Man (T.A. Miettinen) ...... 311 Effects of Dietary Changes on Plasma Lipoprotein Lipids (H. Nakamura, T. Ishikawa, N. Suzuki) ...... 316 Hypolipidemic Diets and Biliary Lipid Composition (G. Schlierf, A. Stiehl, c.c. Heuck, M. Kohlmeier, P. Oster, B. Schellenberg) ...... 320

Workshop: Immunology (Co-Chairpersons: J.D. Mathews, C.R. Minick)

Interaction of Genetic and Environmental Factors Causing Atherosclerosis by Im- munologic Mechanisms (J.D. Mathews) ...... 324 Immunologic Arterial Injury and Atherogenesis (C.R. Minick) ...... 330 Autoimmune Hyperlipidemia and Autoimmune Xanthomatosis (J.L. Beaumont, M.F. Baudet, C. Dachet, V. Beaumont) ...... 334 Tobacco, Immunologic Injury, and Cardiovascular Disease (CG. Becker, T. Dubin) 337 Immunoregulatory Lipoproteins, Viral Hepatitis, and Cancer (F.V. Chisari) ...... 340 Regulation of Pathways of Lymphocyte Differentiation by the Serum Lipoprotein: LDL-In (T.S. Edgington, O.K. Fujii, L.K. Curtiss) ...... 344 Autoimmune Mechanisms in the Development of Atherosclerosis (A.N. Klimov, V.A. Nagornev, Y.N. Zubzhitsky, A.D. Denisenko) ...... 348

Workshop: Animal Models (Co-Chairpersons: T.B. Clarkson, H.C. McGill)

Nutritional Factors in Atherosclerosis (D. Kritchevsky) ...... 351 Cholesterol-Induced Hyperlipoproteinemia and Atherosclerosis in Dogs, Swine and Monkeys: Models for Human Atherosclerosis (R. W. Mahley) ...... 355 Dietary Animal Models for Studying Cardiovascular Disease Risk Factors (S.R. Srinivasan, B. Radhakrishnamurthy, E.R. Dalferes, Jr., G.S. Berenson) ..... 359 Transformation of Naturally Occurring Quiescent Intimal Smooth Muscle Cell Masses into Atherosclerotic Lesions in Swine Fed a Hyperlipidemic Diet (W.A. Thomas, J.M. Reiner, R.A. F1orentin, R.F. Scott, K.T. Lee) ...... 365 Reversal of Atherosclerosis: Comparison of Non-Human Primate Models (D. Ves- selinovitch, R.W. Wissler) ...... 369

Workshop: Enzymes of Lipoprotein Metabolism (Co-Chairpersons: J.A. Glomset, K.R. Norum)

Triglyceride Hydrolysis by Lipoprotein Lipase Bound to Endothelial Cells in Culture (P. Wang-Iverson, E.A. Jaffe, W.V. Brown) ...... 375 LDL-mediated Endocytosis and Cholesteryl Ester Transfer~Alternative Metabolic xvi Pathways for the Regulation of Cellular Cholesterol Synthesis (C.J. Fielding, P.E. Fielding) ...... 379 Mode of Action of the Hepatic Endothelial Lipase: Recycling Endocytosis via Coated Pits (P.K.J. Kinnunen, I. Virtanen) ...... 383 Lipoprotein Lipase and Hepatic Endothelial Lipase are Key Enzymes in the Metabolism of Plasma High Density Lipoproteins, Particularly of HDL2 (E.A. Nikkilii, T. Kuusi, K. Harno, M. Tikkanen, M.R. Taskinen) ...... 387 How Does Lipoprotein Lipase Bind to Substrate Lipoproteins and How Is Its Activity Regulated? (T. Olivecrona, G. Bengtsson) ...... 393 Activation of Lipoprotein Lipase by Synthetic Fragments of ApoC-II (L.C. Smith, J.C. Voyta, A.L. Catapano, P.K.J. Kinnunen, A.M. Gotto, Jr., J.T. Sparrow) .. 397

Plenary Session: The Vessel Wall in Atherosclerosis (Co-Chairpersons: J .F. Mustard, R.W. Wissler)

The Vessel Wall and Atherosclerosis (J.F. Mustard) ...... 403 The Artery Wall and the Pathogenesis of Progressive Atherosclerosis (R. W. Wissler) 407 EIidothelial Dysfunction and the Pathogenesis of Atherosclerosis (M.A. Gimbrone, Jr.) ...... 415 Prostacyclin and Thromboxane A2 in Platelet Vessel Wall Interactions (S. Moncada) 426 The Platelet-Derived Growth Factor (R. Ross, A. Vogel, E. Raines, B. Kariya) ... 442

Workshop: Non-Dietary, Non-Pharmacological Treatment of Hyperlipidemia (Co-Chairpersons: T.E. Starzl, G.R. Thompson)

Portacaval Shunt for Type II Hyperlipidemia (T.E. Starzl, L. Koep, R. Weil, III) 450 Combined Medico-Surgical Strategy for Severe Familial Hypercholesterolaemia (G. Thompson, N. Myant, C. Oakley, R. Steiner, R. Sapsford) ...... 454 Plasma Exchange in the Treatment of Familial Hypercholesterolemia (G .M.B. Berger, F. Bonnici, H.S. Joffe, D.W. Dubovsky) ...... 458 Partial Ileal Bypass: A Test of the Lipid-Atherosclerosis Hypothesis (H. Buchwald, R.B. Moore, R.L. Varco) ...... 462 Selective Removal of Low Density Lipoproteins from Blood by Affinity Chromatog- raphy (P.-J. Lupien, S. Moorjani, M. Lou) ...... 466 Comparison of Cholestyramine, Ileal By-Pass and Portacaval Shunt in the Treatment of Familial Hypercholesterolemia (T.A. Miettinen) ...... 470 Homozygous Hypercholesterolemia; Treatment by Portacaval Shunt (E.A. Stein, C.J. Glueck) ...... 474

Workshop: HDL: Negative Risk Factor for Coronary Heart Disease (Co• Chairpersons: W.P. Castelli, F.H. Epstein)

High Density Lipoproteins: An Overview (W.P. Castelli) ...... 478 Role of HDL in Individual Prediction and Community Prevention of Coronary Heart Disease (F.H. Epstein) ...... 484 Cross-Cultural, Ethnic, Demographic, and Environmental Factors Affecting High Den- sity Lipoprotein Cholesterol and Their Mutual Interrelationships with Coronary

xvii Heart Disease (C.I. Glueck, I.A. Morrison, P.S. Gartside, P. Laskarzewski, K.A. Kelly, S. Mendoza) ...... 488 Epidemiology and High Density Lipoproteins (T. Gordon) ...... 495 HDL Cholesterol, Tissue Cholesterol and Coronary Atherosclerosis: Epidemiological Correlations (N.E. Miller) ...... 500

Workshop: Clinical Trials (Co-Chairpersons: W.T. Friedewald, 1. Stamler)

The Multiple Risk Factor Intervention Trial (W.L. Holmes) ...... 504 Test of the Lipid Hypothesis: The Coronary Primary Prevention Trial (CPPT) of the Lipid Research Clinics Program (R.H. Knopp) ...... 509 The Chicago Heart Health Curriculum Program (I.A. Schoenberger, A.I. Sunseri, 1. Kruc, L. Bickman) ...... 513

Workshop: The Arterial Wall-II (Co-Chairpersons: D.M. Small, E.B. Smith)

Summary of Concepts Concerning the Arterial Wall and Its Atherosclerotic Lesions (D.M. Small) ...... 520 Transport of Macromolecules Across the Artery Wall (E.B. Smith) ...... 525 Cholesteryl Ester-Rich Lipid Inclusions in the Development of Experimental Atherosclerosis in Rabbits (Y. Hata, H. Shigematsu, K. Aihara, M. Yamamoto, Y. Yamauchi, T. Oikawa) ...... 529 Low Density Lipoproteins in the Aorta: Relation to Atherosclerosis (H.F. Hoff, C.L. Heideman, I.W. Gaubatz) ...... 533 Cyclic Nucleotides and Atherosclerosis (F. Numano) ...... 537 Differences in the Metabolism of Abnormal Atherogenic Low Density Lipoproteins from Cholesterol-Fed Nonhuman Primates by Cells in Culture (R.W. St. Clair) 541

Workshop: Vessel Wall-Platelet Interaction (Co-Chairpersons: H .R. Baumgartner, G.V.R. Born)

Factor VIII/Willebrand Factor and the Interaction of Blood Platelets with Suben- dothelium (H.R. Baumgartner, T.B. Tschopp) ...... 546 Do Platelets Contribute to Atherogenesis? (G.V.R. Born) ...... 550 Platelet and Endothelial Alterations in Experimental Arteriosclerosis (L.A. Harker) 557 Endothelium in Experimental Atherosclerosis (C.R. Minick, D.I. Falcone, D.P. Haiiar) ...... 563 Smooth Muscle Cell Kinetics In Vivo: A Comparative Study (M.B. Stemerman, LD. Goldberg, R.T. Gardner, R.L. Fuhro) ...... 567

Workshop: Catabolism of Lipids, Apolipoproteins and Lipoproteins (Co• Chairpersons: D.S. Goodman, P.I. Nestel)

Turnover and Metabolism of Body Cholesterol in Humans (D.S. Goodman, F .R. Smith, A.H. Seplowitz, R. Ramakrishnan, R.B. Dell) ...... 570

xviii Turnover of Very Low Density Lipoprotein Proteins (P.J. Nestel, N.H. Fidge) .... 576 Low Density Lipoprotein Metabolism in Familial Hypercholesterolemia (D. W. Bilheimer) ...... 580 Metabolism of Very Low Density Lipoprotein-Triglyceride in Man (S.M. Grundy) 586 Effects of Drugs on High Density Lipoprotein Metabolism (J. Shepherd, C.J. Packard) 591 Liver and Cholesteryl Ester Transfer Amongst Lipoprotein-One Suggested Model (A. Sniderman, B. Teng) ...... 596 Role of Chylomicrons in Atherogenesis (D.B. Zilversmit) ...... 600

Plenary Session: Plasma Lipids, Lipoproteins and Atherosclerosis (Co• Chairpersons: A.M. Scanu, D. Steinberg)

Relationship Between the Properties of the Apo B Containing Low-Density Lipopro• teins (LDL) of Normolipidemic Rhesus Monkeys and their Mitogenic Action on Arterial Smooth Muscle Cells Grown In Vitro (G.M. FIess, T. Kirchhausen, K. Fischer-Dzoga, R.W. Wissler, A.M. Scanu) ...... 607 Lipoprotein Structure and Metabolism: Inhomogeneity, Variability and Species Specificity (D. Steinberg) ...... 616 Structure and Function of the Human Plasma Apolipoproteins (H.J. Pownall, J.T. Sparrow, L.c. Smith, A.M. Gotto, Jr.) ...... 624 Enzymatic Regulation of Lipoprotein Catabolism (H. Greten, J. Grosser, I. Becht, O. Schrecker, K. Preissner, G. Klose) ...... 631 Cholesterol Feeding: Effects on Lipoprotein Structure and Metabolism (R. W. Mahley) 641 Metabolism of Plasma Lipoproteins (Y. Stein, O. Stein) ...... 653

Workshop: Mutants Affecting Lipoproteins and Apoproteins (Co-Chairpersons: G. Assmann, J. A. Little)

Possible Mechanisms of Lipid Storage in Tangier Disease (G. Assmann, H.-E. Schaefer) ...... 666 Introduction to Deficiencies of Apolipoproteins ClI and EIII With Some Associated Clinical Findings (l.A. Little, D. Cox, W.C. Breckenridge, V.M. McGuire) .. 671 Apolipoprotein ClI Deficiency (W.C. Breckenridge, D. Cox, J.A. Little) ...... 675 Tangier Disease (H.B. Brewer, Jr., E.J. Schaefer, L.A. Zech, T.J. Bronzert) ..... 680 Abetalipoproteinemia and Hypobetalipoproteinemia: Questions Still Exceed Insights (P.N. Herbert, R.J. Heinen, L.L. Bausserman, K.M. Lynch, L.O. Henderson, T.A. Musliner) ...... 684 Polymorphism of Apolipoprotein E (G. Utermann) ...... 689

Workshop: Hypertension (Co-Chairpersons: J.M. Laragh, J.R. Mitchell)

Renin Sodium Profiling and Vasoconstriction Volume Analysis of Hypertensive Pa- tients. A New Era for Diagnosis and Treatment (l.H. Laragh) ...... 695 Aortic Endothelial Changes During the Development and Reversal of Experimental Hypertension (A.V. Chobanian, M.F. Prescott, C.C. Haudenschild) ...... 699 Atherosclerosis and Its Risk Factors in Japan (Y. Goto) ...... 703

xix Controlled Therapeutic Trial in Mild Hypertension-Initial Results (R. Lovell) .... 707 Clinical and Pathogenic Relevance of Erythrocyte Cation Fluxes Measurement in Human Hypertension (R.P. Garay, J.-L. Elghozi, G. Dagher, P. Meyer) 712

Workshop: Regression (Co-Chairpersons: D.H. Blankenhorn, J.P. Strong)

Estimated Rates of Progression and Regression of Human Femoral and Coronary Atherosclerosis in 45-Year-Old Men (D.H. Blankenhorn) ...... 715 Community Pathology of Atherosclerosis and Coronary Heart Disease in New Orleans: Relationship of Risk Factors to Atherosclerotic Lesions (J.P. Strong, W.D. Johnson, M.C. Oalmann, R.E. Tracy, W.P. Newman, III, W.A. Rock, G.T. Malcom, M.G. Kokatnur, V. Toca) ...... 719 Regression Sequences After Experimental Atherosclerosis (M.L. Armstrong, M.B. Megan, E.D. Warner) ...... 731 Changes in Atherosclerotic Lesions Following Surgical Cholesterol Reduction (H. Buchwald, R.D. Rucker, R.B. Moore, R.L. Varco) ...... 735 Approaches to the Study of Atherosclerosis Regression in Rhesus Monkeys: Interpreta- tion of Morphometric Measurements of Coronary Arteries (T.B. Clarkson, M.G. Bond, C.A. Marzetta, B.C. Bullock) ...... 739 Regression of Advanced Atherosclerotic Lesions in Swine (A.S. Daoud, J. Jarmolych, J.M. Augustyn, K.E. Fritz) ...... 749 Differences in the Degradation-Rate of Intracellular Lipid Droplets in the Intimal Smooth Muscle Cells and Macrophages of Regressing Atherosclerotic Lesions of Primates (H. Chr. Stary, J.P. Strong, D.A. Eggen) ...... 753 Quantitating Rhesus Monkey Atherosclerosis Progression and Regression with Time (R.W. Wissler, D. Vesselinovitch, T.J. Schaffner, S. Glagov) ...... 757

Workshop: The Interrelationship Between Lipid and Prostaglandin Metabolism (Co-Chairpersons: S. Bergstrom, G.S. Boyd)

Prostacyclin and Atherosclerosis-A Hypothesis (R.J. Gryglewski) ...... 762 Modulation by Prostaglandins of Vascular Reactivity to Adrenergic Stimuli (K.U. Malik, A. Nasjletti) ...... 766 Prostaglandins, Thrombin Receptors and Platelet Aggregation in Normal and Hyper- cholesterolemic Subjects (R. Paoletti, E. Tremoli) ...... 772 Prostaglandins, Thromboxanes and Leukotrienes (B. Samuelsson) ...... 776

Workshop: CeUular Metabolism of Lipoproteins (Co-Chairpersons: E.L. Bierman, N. Myant)

Role of Hormones Associated with Atherogenesis in Modulating Cellular Metabolism of Lipoproteins (E.L. Bierman) ...... 784 Platelet Production of Pathological LDL (A.M. Fogelman, I. Shechter, J. Seager, M. Hokom, J.S. Child, P.A. Edwards) ...... 787 Modulation of Cellular Cholesterol Metabolism by LCAT Treated Lipoproteins (G. Rothblat, F. Bellini, E. Ray) ...... 791 xx Deposition and Hydrolysis of Cytoplasmic Triglyceride and Cholesterol Ester in Aortic Smooth Muscle Cells in Culture (0. Stein, G.A. Coetzee, Y. Stein) ...... 796 The Role of the Liver in LDL Catabolism (D. Steinberg, R.C. Pittman, A.D. Attie, T.E. Carew, S. Pangburn, D. Weinstein) ...... 800

Workshop: Apoprotein Quantification (Co-Chairpersons: P. Alaupovic, D. Seidel)

Standardization of Apolipoprotein Immunoassays by an Isotope Dilution Method (P. Weech, W.J. McConathy, P. Alaupovic, J. Fesmire) ...... 804 Rate-Nephelometry of A-I and Electrophoresis (N. Weinstock, M. Barthoiome, D. Seidel) ...... 807 Methodological Considerations in Apolipoprotein Immunoassay (1.J. Albers, M.C. Cheung, C.-H. Floren) ...... 811 Plasma Levels of Some Apolipoproteins in Human Atherosclerosis (P. Avogaro, G.B. Bon, G. Cazzolato, G. Quinci, F. Belussi) ...... 816 Quantitation of C Apolipoprotein Metabolism in Human Subjects (N.H. Fidge, P.J. Nestel, M.W. Huft) ...... 820 Quantitation of Apolipoproteins C-II and C-III in Plasma (G. Schonfeld) ...... 824

Index ...... 831

xxi CONTRIBUTORS

C.W.M. Adams, M.D., D.Sc., F.R.C.P., F.R.C. Path., Head, Department of Pathology, Guy's Hospital Medical School, London SEI 9RT, England Edward H. Ahrens, Jr., M.D., The Rockefeller University, 1230 York Avenue, New York, New York 10021, U.S.A. Kazuo Aihara, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Petar Alaupovic, Ph.D., Head, Lipoprotein Laboratory, Oklahoma Medical Research Foun• dation, 825 Northeast 13th Street, Oklahoma City, Oklahoma 73104, U.S.A. John J. Albers, Ph.D., Division of Metabolism and Endocrinology, Department of Medicine, Harborview Medical Center, University of Washington School of Medicine, 326 Ninth Avenue, Seattle, Washington 98104, U.S.A. Mark L. Armstrong, M.D., Cardiovascular Division, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, U.S.A. Gerd Assmann, M.D., Westfalische Wilhelms-Universitiit, Medizinische Einrichtungen Zentrallaboratorium, 44 Munster, Westring 3, Federal Republic of Germany Alan D. Attie, Division of Metabolic Disease, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A. W. Auerswald, M.D., Atherosclerosis Research Group at the Department of Medical Physiology, University of Vienna, Vienna, Austria Josef Augustin, M.D., Klinisches Institut fUr Herzinfarktforschung an der Medizinisches, Universitiitsklink Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Re• public of Germany J.M. Augustyn, Ph.D., Laboratory Service, Veterans Administration Medical Center, Al• bany, New York 12208, U.S.A. Pietro Avogaro, M.D., Ph.D., Regional General Hospital, Unit for Atherosclerosis, Na• tional Council for Research, 30100 Venice, Italy Giovannella Baggio, M.D., Department of Internal Medicine, Division of Gerentology and Metabolic Diseases, University of Padua, Policlinico, Via Giustiniani 2, 35100 Padua, Italy Margret Bartholome, Ph. D., Lehrstuhl fUr Klinischen Chemie der Medizinischen Ein• richtungen der Universitiit Gottingen, Robert-Koch-Strasse 40, 3400 Gottingen, Federal Republic of Germany M.F. Baudet, Ph.D., INSERM U 32, Creteil Faculty of Medicine, Henri-Mondor Hospital, Paris xn University, 9400 Creteil, France Hans R. Baumgartner, M.D., F. Hoffman-La Roche and Company, Department of Phar• macology Research, CH 4002 Basel, Switzerland Linda L. Bausserrnan, Ph.D., Brown University Program in Medicine, The Miriam Hospi• tal, 164 Summit Avenue, Providence, Rhode Island 02906 O.B. Bayliss-High, Ph.D., M. Phil., Department of Pathology, Guy's Hospital Medical School, London SEI 9RT, England

xxiii J.L. Beaumont, M.D., INSERM U 32, Creteil Faculty of Medicine, Henri-Mondor Hospital, Paris XII University, 9400 Creteil, France V. Beaumont, M.D., INSERM U 32, Creteil Faculty of Medicine, Henri-Mondor Hospital, Paris XII University, 9400 Creteil, France Isolde Becht, Kliniches Institut fiir Herzinfarktforschung an der Medizinischen, Univer• sitatsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Carl Becker, M.D., Department of Pathology, The New York Hospital, Cornell Medical Center, 525 East 68th Street, New York, New York 10021, U.S.A. Fabrizio Bellini, Ph.D., Departments of Physiology and Biochemistry, The Medical College of Pennsylvania Hospital, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, U.S.A. Fabio Belussi, M.D., Regional General Hospital, Unit for Atherosclerosis, National Council for Research, 30100 Venice, Italy Gunilla Bengtsson, Ph.D., Department of Medical Chemistry, University of Umea, S901 87 Umea, Sweden Gerald S. Berenson, M.D., Head, Section of Cardiology, Department of Medicine, Director, Specialized Center of Research-Atherosclerosis, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. G. Michael B. Berger, M.B., Ch.B., Ph.D., Department of Pathology and Lipid Clinic, Red Cross War Memorial Children's Hospital, Randelbosch 7700, Cape Town, Republic of South Africa Leonard Bickman, Ph.D., W.:stinghouse National Issues Center, Chicago, Illinois, U.S.A. Edwin L. Bierman, M.D., Head, Division of Metabolism and Endocrinology, University of Washington School of Medicine, RG Royal Gorge 20, Seattle, Washington 98195, U.S.A. David W. Bilheimer, M.D., Department of Internal Medicine, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235, U.S.A. Soren Bjokerud, M.D., Ph.D., Department of Pathology, University of Goteborg, Sahlgrens Hospital, S-41345 Goteborg, Sweden Henry W. Blackburn, M.D., Director, Laboratory of Physiological Hygiene, School of Public Health, University of Minnesota School of Medicine, 611 Beacon Street SE, Minneapolis, Minnesota 55455, U.S.A. Ralph Blackett, M.D., Chairman, Department of Medicine, Prince Henry and Prince of Wales Hospitals, University of New South Wales, Sydney, New South Wales, Australia David H. Blankenhorn, M.D., Director, Cardiology Division, Department of Medicine, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033, U.S.A. Donna Boggs, R.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Gabriele Bittolo Bon, M.D., Regional General Hospital, Unit for Atherosclerosis, National Council for Research, 30100 Venice, Italy M. Gene Bond, Ph.D., Arteriosclerosis Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103, U.S.A. Francois Bonnici, M.B., Ch.B., M.Med., F.C.P., Department of Pediatrics and Lipid Clinic, Red Cross War Memorial Children's Hospital, Cape Town, Republic of South Africa G.V.R. Born, F.R.C.P., F.R.S., Department of Pharmacology, University of London King's College, Strand, London WC2R 2LS, England

xxiv Fred Brand, M.D., Department of Medicine, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. W. Carl Breckenridge, Ph.D., Lipid Research Clinic, Departments of Medicine and Clinical Biochemistry, University of Toronto, I Spadina Crescent, Toronto M5S 2J5, Ontario, Canada PJ. Brennan, M.B., F.R.A.C.P., Staff Physician, Prince Henry and Prince of Wales Hospi• tals, Sydney, New South Wales, Australia H. Bryan Brewer, Jr., M.D., Chief, Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 7N1l7, 9000 Rockville Pike, Bethesda, Maryland 20205, U.S.A. T.J. Bronzert, Molecular Disease Branch, National Heart, Lung and Blood Institute, Na• tional Institutes of Health, Bethesda, Maryland 20205, U.S.A. Virgil Brown, M.D., Chief, Division of Arteriosclerosis and Metabolism, Department of Medicine, Mount Sinai Medical Center, 1 Gustav Levy Place, New York, New York 10029, U.S.A. Henry Buchwald, M.D., Ph.D., Department of Surgery, Medical School, University of Minnesota, 516 Delaware Street SE, Minneapolis, Minnesota 55455, U.S.A. Bill C. Bullock, D.V.M., Arteriosclerosis Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103, U.S.A. Kathryn Burton, R.D., Lipid Research and General Clinical Research Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. German Camejo, Ph.D., Head, Laboratorio de Lipoproteinas, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Apartado 1827, Caracas-lO I, Venezuela Alan D. Cardin, Ph.D., Department of Pharmacology and Biophysics, University of Cincin• nati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Thomas E. Carew, Ph.D., Division of Metabolic Disease, School of Medicine, University of California, San Diego, La Jolla, California 92093, U.S.A. William P. Castelli, M.D., Medical Director, Heart Disease Epidemiology Study, National Heart, Lung and Blood Institute, National Institutes of Health, 118 Lincoln Street, Framingham, Massachusetts 01701, U.S.A. Alberico L. Catapano, Ph.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Farmacognosia, Universita di Milano, Via A. Del Sarto 21, 20129 Milano, Italy Giuseppe Cazzolato, Ph.D., Regional General Hospital, Unit for Atherosclerosis, National Council for Research, 30100 Venice, Italy Marian Cheung, Ph.D., Division of Metabolism and Endocrinology, Department of Medicine, University of Washington School of Medicine, Harborview Medical Center, 732 Harborview Hall ZA-36, 326 Ninth Avenue, Seattle, Washington 98104, U.S.A. G.G. Chetchinachvili, M.D., Institute of Experimental Medicine, Academy of Medical Science USSR, Kirovsky 69/71, Leningrad 197022, U.S.S.R. John S. Child, M.D., Division of Cardiology, Department of Medicine, University of California Center for the Health Sciences, Los Angeles, California 90024, U.S.A. Francis V. Chisari, M.D., Department of Molecular Immunology, Scripps Clinic and Re• search Foundation, 10666 North Torry Pines Road, La Jolla, California 92037, U.S.A. Aram V. Chobanian, M.D., Director, Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. William R. Clarke, Ph.D., Department of Preventive Medicine, Division of Biostatistics, University oflowa, Iowa City, Iowa 52242, U.S.A. Thomas B. Clarkson, D.V.M., Department of Comparative Medicine, Director,

xxv Atherosclerosis Research Center, Bowman Gray School of Medicine of Wake Forest University, 300 South Hawthorne Road, Winston-Salem, North Carolina 27103, U.S.A. Diane Wilson Cox, Ph.D., F.C.C.M.G., Departments of Pediatrics and Genetics, Hospital for Sick Children, Departments of Medical Genetics and Medical Biophysics, Univer• sity of Toronto, 555 University Avenue, Toronto, Ontario, Canada Gaetano Crepaldi, M.D., Director, Department of Internal Medicine, Division of Gerentol• ogy and Metabolic Diseases, University of Padua, Policlinico, Via Giustiniani 2, 35100 Padua, Italy Linda K. Curtiss, Ph.D., The Research Institute "Of Scripps Clinic, Department of Molecular Immunology, 10666 North Torrey Pines Road, La Jolla, California 92037, U.S.A. Georges Dagher, M.S., INSERM U 7 Research Unit, Hopital Necker, 161 rue de Sevres, 74015 Paris, France E.R. Dalferes, Jr., B.S., Department of Medicine, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Assaad S. Daoud, M.D., Chief, Laboratory Service, Veterans Administration Medical Center, Department of Pathology, Albany Medical College, 113 Holland A venue, Albany, New York 12208, U.S.A. Jean Davignon, M.D., M.Sc., F.R.C.P., F.A.C.P., Director, Department of Lipid Metabo• lism and Atherosclerosis Research, Clinical Research Institute of Montreal, Department of Medicine, University of Montreal, 110 Avenue des Pins Ouest, Montreal, Quebec H2W lR7, Canada Roger A. Davis, Ph.D., Division of Metabolic Disease, Department of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A. Michael E. DeBakey, M.D., Olga Keith Wiess Professor of Surgery, Chairman, Department of Surgery, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. Ralph B. Dell, M.D., Arteriosclerosis Research Center and the Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A. A.D. Denisenko, M.D., Institute for Experimental Medicine, Academy of Medical Science U.S.S.R., Kirovsky 69171, Leningrad 197022, U.S.S.R. Theodore Dubin, D.V.M., Department of Pathology, The New York Hospital, Cornell University Medical Center, New York, New York 10021, U.S.A. Charles Dubost, M.D., Clinique Chirurgicale Cardiovasculaire, Hospital Broussais, 96 Rue Didot, 75674 Paris, Cedex 14, France Daniel W. Dubovsky, M.B., Ch.B., F.C.P., Department of Hematology, University of Cape Town Medical School, Cape Town, Republic of South Africa Thomas S. Edgington, M.D., Department of Molecular Immunology, The Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California 92037, U.S.A. Peter A. Edwards, Ph.D., Division of Cardiology, Department of Medicine, University of California for the Health Sciences, Los Angeles, California 90024, U.S.A. Douglas A. Eggen, Ph.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Shlomo Eisenberg, M.D., Lipid Research Laboratory, Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel Jean-Luc Elghozi, M.D., INSERM U 7 Research Unit, Hopital Necker, 161 rue de Sevres, 75015 Paris, France Akira Endo, M.D., Fermentation Laboratory, Tokyo, Noko University, 3-5-8 Saiwaicho, Fuchu-shi, Tokyo, 183 Japan xxvi Sven Chr. Enger, M.D., Department of Pathology, Ullevaal Hospital, Oslo, Norway Sheldon G. Englehorn, Division of Metabolic Disease, Department of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A. Frederick H. Epstein, M.D., Institut fur Sozial- und Priiventivmedizin, Universitiit Zurich, Gloriastrasse 32, 8006 ZUrich, Switzerland Domenick J. Falcone, B.A., Department of Pathology, The New York Hospital-Cornell Medical Center, 625 East 68th Street, New York, New York 10021, U.S.A. Renato Fellin, M.D., Department of Internal Medicine, Division of Gerentology and Metabolic Diseases, University of Padua, Policlinico, Via Giustiniani 2, 35100 Padua, Italy James Fesmire, B. S., Laboratory of Lipid Research and Lipoprotein Studies, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, U.S.A. Noel H. Fidge, Ph.D., Cardiovascular Metabolism and Nutrition Research Unit, Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia 3181 Christopher 1. Fielding, Ph.D., Cardiovascular Research Institute, University of California, San Francisco, California 94143, U.S.A. Phoebe E. Fielding, Ph.D., Cardiovascular Research Institute, University of California, San Francisco, California 94143, U.S.A. Katti Fischer-Dzoga, M.D., Department of Pathology, The University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. Gunther M. Fless, Ph.D., Department of Medicine, The University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. C.-H. Floren, M.D., Division of Metabolism and Endocrinology, Department of Medicine, University of Washington School of Medicine, Harborview Medical Center, Seattle, Washington 98104, U.S.A. R.A. Florentin, M.D., Department of Pathology, Albany Medical College of Union Univer• sity, 47 New Scotland Avenue, Albany, New York 12208, U.S.A. Alan Marcus Fogelman, M.D., Division of Cardiology, Department of Medicine, University of California Center for the Health Sciences, Los Angeles, California 90024, U.S.A. G. Franceschini, Ph.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Far• macognosia, Universita di Milano, Via A. Del Sarto 21, 20129 Milano, Italy Ivan D. Frantz, M.D., Department of Medicine and Biochemistry, University of Minnesota Medical School, Minneapolis, Minnesota 55455, U.S.A. K.E. Fritz, Ph.D., Atherosclerosis Research, Veterans Administration Medical Center, Al• bany, New York 12208, U.S.A. Dennis K. Fujii, Ph.D., Department of Molecular Immunology, The Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California 92037, U.S.A. Ricardo P. Garay, M.D., INSERM U 7 Research Unit, Hopital Necker, 161 rue de Sevres, 75015 Paris, France Ruth T. Gardner, Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts 02215, U.S.A. Peter S. Gartside, Ph.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Antoine Gattereau, M.D., M.Sc., F.R.C.P., F.A.C.P., Department of Medicine, University of Montreal, Department of Lipid Metabolism and Atherosclerosis Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada John W. Gaubatz, M.S., Department of Medicine, Baylor College of Medicine, 1200 Mour• sund, Houston, Texas 77030, U.S.A. Ross G. Gerrity, Ph.D., Cleveland Clinic Foundation, 9500 Euclid, Cleveland, Ohio 44106, U.S.A.

xxvii Godfrey S. Getz, M.B., B.Ch. D. Phil., Departments of Pathology and Biochemistry and Specialized Center of Research in Atherosclerosis, University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. G.J. Gherardi, M.D., Department of Pathology, Framingham Union Hospital, Framingham, Massachusetts, U.S.A. G. Gianfranceschi, Ph.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Farmacognosia, Universita di Milano, Via A. Del Sarto 21,20129 Milano, Italy Peter Giles, Ph.D., D.LC., M.I. BioI., Department of Child Health, Institute of Child Health, 30 Guilford Street, London WCIN lEN, England Dr. Michael A. Gimbrone, Jr., Department of Pathology, Harvard Medical School and the Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115, U.S.A. S. Glagov, M.D., Department of Pathology, University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. Leonora Glatfelter, R.D., Lipid Research and General Clinical Research Centers, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229, U.S.A. Robert M. Glickman, M.D., Department of Medicine, Chief of Gastroenterology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York. New York 10032, U.S.A. Charles J. Glueck, M.D., Director, Lipid Research and General Clinical Research Centers. University of Cincinnati. College of Medicine, 234 Goodman Street, Cincinnati, Ohio 45229, U.S.A. Itzhak Goldberg, M.D., Harvard Medical School and Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215, U.S.A. DeWitt S. Goodman, M.D., Tilden-Weger-Bieler Professor, Arteriosclerosis Research Center and the Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A. John F. Goodwin, M.D., F.R.C.P., F.A.C.C., Department of Clinical Cardiology, Univer• sity of London, Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London W12 OHS, England Tavia Gordon, 12901 Blue Hill Road, Silver Springs, Maryland 20906, U.S.A. Yuichiro Goto, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Antonio M. Gotto, Jr., M.D., The J.S. Abercrombie Professor of Atherosclerosis and Lipoprotein Research, Chairman, Department of Medicine, Baylor College of Medicine, The Bob and Vivian Smith Professor and Chairman, Department of Internal Medicine, The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. Peter H.R. Green, F.R.A.C.P., Department of Medicine, Division of Gastroenterology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A. Heiner Greten, M.D., Klinisches Institut fur Herzinfarktforschung an der Medizinischen, Universitiitsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Jochen Grosser, M.D., Klinisches Institut fur Herzinfarktforschung an der Medizinischen, Universitiitsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Scott M. Grundy, M. D., Ph. D., Department of Medicine, Veterans Administration Medical Center and The University of California, San Diego, California 92161, U.S.A. Ryszard J. Gryglewski, M.D., Chairman, Department of Pharmacology, N. Copernicus Medical Academy, 31-531 Cracow, Grzeg6rzecka 16 Poland xxviii Daniel L. Guerrero, B.A., Department of Pathology, The University of Texas Health Sci• ence Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, U.S.A. M. Robin Hagens, B.S., Department of Pathology, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, U.S.A. David P. Hajjar, Ph.D., Department of Pathology, The New York Hospital-Cornell Medi• cal Center, 625 East 68th Street, New York, New York 10021, U.S.A. Robert L. Hamilton, Ph.D., Cardiovascular Research Institute, University of California, San Francisco, California 94122, U.S.A. Laurence A. Harker, M. D ., Division of Hematology, Department of Medicine, U ni versity of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, Washington 98105, U.S.A. Kari Hamo, M.D., Third Department of Medicine, University of Helsinki Central Hospital, 00290 Helsinki 29, Finland Yoshiya Hata, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Christian C. Haudenschild, M.D., Department of Pathology, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. Helmut Hauser, Ph.D., Institut fur Biochemie ETH, Zurich, Switzerland M. Daria Haust, M.D., Departments of Pathology and Pediatrics, University of Western Ontario and University Hospital Health Sciences Center, London N6A 5Cl, Ontario, Canada Richard 1. Havel, M.D., Cardiovascular Research Institute, University of California, San Francisco, California 94143, U.S.A. Rick Hay, M.D., Ph.D., Department of Pathology, The University of Chicago Hospitals and Clinics and The Pritzker School of Medicine, Chicago, Illinois 60637, U.S.A. T. Hayashi, M.D., Honolulu Heart Study, Kuakini Medical Center, 347 North Kuakini Street, Honolulu, Hawaii 96817, U.S.A. William R. Hazzard, M.D., Chief, Division of Gerontology and Geriatric Medicine, North• west Lipid Research Clinic, University of Washington School of Medicine, 326 Ninth Avenue, Seattle, Washington 98104, U.S.A. Carol L. Heideman, M.S., Department of Medicine, Baylor College of Medicine, 1200 Moursund, Houston, Texas 77030, U.S.A. Robert J. Heinen, M.D., Brown University Program in Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906, U.S.A. G. Heiss, M.D., Ph.D., Lipid Research Clinic Program, Central Patient Registry and Coor• dinating Centers, Department of Biostatistics, School of Public Health, University of North Carolina, Chapel Hill, North Carolina, U.S.A. Anders Helgeland, M.D., Department of Pathology, Ullevaal Hospital, Oslo, Norway L. Omar Henderson, Ph.D., Brown University Program in Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island, 02906, U.S.A. Peter N. Herbert, M.D., Brown University Program in Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906, U.S.A. C.C. Heuck, M.D., Ph.D., Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, D6900 Heidelberg, Federal Republic of Germany Ingvar Hjermann, M.D., Department of Pathology, Ullevaal Hospital, Oslo, Norway Henry F. Hoff, Ph.D., Department of Medicine, Baylor College of Medicine, 1200 Mour• sund, Houston, Texas 77030, U.S.A. Martha Hokom, B.S., Division of Cardiology, Department of Medicine, University of California Center for the Health Sciences, Los Angeles, California 90024, U.S.A. Ingar Holme, M.D., Department of Pathology, Ullevaal Hospital, Oslo, Norway

xxix William L. Holmes, Ph.D., Chairman, Department of Research, Lankenau Hospital, Lan• caster Avenue West of City Line, Philadelphia, Pennsylvania 19151, U.S.A. Murray W. Huff, Ph.D., Cardiovascular Metabolism and Nutrition Research Unit, Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia 3181 Donald B. Hunninghake, M.D., Departments of Medicine and Pharmacology, University of Minnesota, 3-260 Millard Hall, 435 Delaware Street SE, Minneapolis, Minnesota 55455, U.S.A. Toshitsugu Ishikawa, M.D., Department of Medicine, Jikei University, Aoto Hospital, 6-41-2 Aoto, Katsushika, Tokyo, Japan Richard L. Jackson, Ph.D., Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Eric A. Jaffe, M.D., Division of Hematology-Oncology, Department of Medicine, The New York Hospital-Cornell Medical Center, 625 East 68th Street, New York, New York 10021, U.S.A. J. Jarmolych, M.D., Chief, Anatomical Pathology, Laboratory Service, Veterans Adminis• tration Medical Center, Albany, New York 12208, U.S.A. Mary Jane Jesse, M.D., Vice-Chairman, Department of Pediatrics, University of Miami School of Medicine, Miami, Florida, U.S.A. Hymie S. Joffe, M.B., Ch.B., M. Med., Department of Pediatrics, Red Cross War Memo• rial Children's Hospital, Cape Town, Republic of South Africa J. David Johnson, Ph.D., Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. W.D. Johnson, M.S., Department of Biometry, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. John P. Kane, M.D., Ph.D., Department of Medicine, Associate Director, Specialized Center of Research on Atherosclerosis, University of California, San Francisco, California 94143, U.S.A. William B. Kannel, M.D., M.P.H., Chief, Section of Preventive Medicine and Epidemiol• ogy, Department of Medicine, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. Beverly Kariya, Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, U.S.A. Kathe A. Kelly, M.Sc., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Phil Khoury, M.S., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Paavo K.J. Kinnunen, M.D., Third Department of Medicine, University of Helsinki Central Hospital, Helsinki 29, Finland Tomas Kirchhausen, Ph.D., Department of Medicine, The University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. Anatoli N. Klimov, M. D., Head, The Anitchkov Department of Atherosclerosis and Labora• tory of Lipid Metabolism, Institute for Experimental Medicine, Academy of Medical Science USSR, Kirovsky 69171, Leningrad, 197022, U.S.S.R. Gerald Klose, M.D., Klinisches Institut fUr Herzinfarktforschung an der Medizinischen, Universitiitsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Roger D. Knapp, Ph.D., Department of Medicine, Baylor College of Medicine and The

xxx Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. Robert H. Knopp, M.D., Director, Northwest Lipid Research Clinic, Department of Medicine, University of Washington School of Medicine, 325 Ninth Avenue, Seattle, Washington 98104, U.S.A. Lawrence Koep, M.D., Department of Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, U.S.A. M. Kohlmeier, M.D., Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, D6900 Heidelberg, Federal Republic of Germany M.G. Kokatnur, Ph.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Gerhard M. Kostner, Ph.D., Institute of Medical Biochemistry, University of Graz, A-8010 Graz, Austria David Kritchevsky, Ph.D., Associate Director, The Wistar Institute of Anatomy and Biol• ogy, University of Pennsylvania, 36th Street At Spruce, Philadelphia, Pennsylvania 19104, U.S.A. Joan Kruc, M.S., Chicago Heart Association, Chicago, Illinois, U.S.A. Timo Kuusi, M.D., Third Department of Medicine, University of Helsinki Central Hospital, 00290 Helsinki 29, Finland Peter o. Kwiterovitch, Jr., M.D., Departments of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A. Peter Laggner, Ph.D., Institut fur RontgenstrukturanaIyse, Steyrergasse 17, Graz, Austria John M. Laragh, M.D., Master Professor of Surgery, Director, Cardiovascular Center, The New York Hospital-Cornell Medical Center, 525 East 68th Street, New York City, 10021, U.S.A. Rhea Larsen, R.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. J. LaRosa, M.D., Director, Lipid Research Clinic, George Washington University Hospital Medical Center, Washington, D.C., U.S.A. Ronald M. Lauer, M.D., Director, Division of Pediatric Cardiology, Department of Pediat• rics, University of Iowa, Iowa City, Iowa 52242, U.S.A. Peter Laskarzewski, Ph.D., Lipid Research and General Clinical Research Centers, Univer• sity of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Gerald M. Lawrie, M.D., M.B.B.S., F.R.C.S., F.R.A.C.S., F.R.C.S., Department of Surgery, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Hous• ton, Texas 77030, U.S.A. K.T. Lee, M.D., Ph.D., Department of Pathology, Albany Medical College of Union University, 47 New Scotland Avenue, Albany, New York 12208, U.S.A. B. Leelarthaepin, Ph.D., Department of Medicine, Prince Henry Hospital, Sydney, New South Wales, Australia Robert I. Levy, M.D., Director, National Heart, Lung and Blood Institute, National Insti• tutes of Health, Building 31, Room 5A-52, Bethesda, Maryland 20205, U.S.A. Paul Leren, M.D., Department of Pathology, Ullevaal Hospital, Oslo, Norway Barry Lewis, M.D., Department of Chemical Pathology and Metabolic Disorders, St. Thomas's Hospital, London SE1 7EH, England J. Alick Little, M.D., F.R.C.P., Lipid Research Clinic, Department of Medicine, St. Michael's Hospital, University of Toronto, 1 Spadina Crescent, Toronto M55 2J5, Ontario, Canada June K. Lloyd, M.D., F.R.C.P., Department of Child Health, St. George's Hospital Medi• cal School, London SW17 ORE, England Madeleine Lou, M.Sc., Centre de Recherches sur les Maladies Lipidiques, Centre Hos• pitalier de l'Universite Laval, 2705 boulevard Laurier, Ste-Foy, Quebec GIV 4G2, Canada Richard Lovell, A.O., Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia Karen M. Lynch, M.S., Brown University Program in Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906, U.S.A. Paul J. Lupien, M.D., Ph.D., Director, Centre de Recherche sur les Maladies Lipidiques, Centre Hospitalier de l'Universite Laval, 2705 Boulevard Laurier, Ste-Foy, Quebec GlV 4G2, Canada Suzanne Lussier-Cacan, Ph.D., Department of Medicine, University of Montreal, Depart• ment of Lipid Metabolism and Atherosclerosis Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada Robert W. Mahley, M.D, Ph.D., Director, Gladstone Research Foundation, Laboratories for Cardiovascular Disease, University of California, San Francisco, California 94110, U.S.A. G. T. Malcom, Ph.D., Departments of Pathology and Medical Technology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70122, U.S.A. Kafait U. Malik, D.Sc., Ph.D., Department of Pharmacology, College of Medicine, Center for the Health Sciences, University of Tennessee, 800 Madison Avenue, Memphis, Tennessee 38163, U.S.A. M.J. Malloy, M.D., Cardiovascular Research Institute, University of California, San Fran• cisco, California 94143, U.S.A. Carol A. Marzetta, B.S., Arteriosclerosis Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103, U.S.A. John Mathews, M.D., Ph.D., F.R.A.C.P., Department of Medicine, University of Mel• bourne, Royal Melbourne Hospital, Victoria 3050, Australia Nohuo Matsuoka, M.D., Ph.D., Department of Pharmacology and Cell Biophysics, Univer• sity of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Walter McConathy, Ph.D., Laboratory of Lipid Research and Lipoprotein Studies, Ok• lahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma, City, Oklahoma 73104, U.S.A. C.A. McGilchrist, Ph.D., School of Mathematics, University of New South Wales, Ken• sington, New South Wales, AustraIia V.M. McGuire, B.S., R.P.Dt., Department of Dietetics, St. Michael's Hospital, 30 Bond Street, Toronto M5B 1W8, Canada Henry D. McIntosh, M.D., Watson Clinic, P.O. Box 1429, Lakeland, Florida 33802, U.S.A. P.M. McNamara, B.S., Framingham Study, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205, U.S.A. Marjorie B. Megan, Department of Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, U.S.A. Margot J. MelIies, M.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Soaira Mendoza, M.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Philippe Meyer, M.D., Departments of Physiology and Pharmacology, INSERM U 7 Re• search Unit, Hopital Necker, 161 rue de Sevres, 75015 Paris, France

xnii Tatu Miettinen, M.D., Second Department of Medicine, University of Helsinki, 00290 Helsinki 29, Finland Norman E. Miller, M.D., M.Sc., Ph.D., Department of Chemical Pathology and Metabolic Disorders, 5th Floor, North Wing, St. Thomas's Hospital Medical School, London SEI 7EH, England Richard R. Miller, M.D., Department of Medicine, Chief of Cardiology, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. C. Richard Minick, M.D., Department of Pathology, The New York Hospital-Cornell Medical Center, 625 East 68th Street, New York, New York 10021, U.S.A. Patricia P. Moll, Ph.D., Department of Human Genetics, The University of Michigan Medical School, 1137 E. Catherine Street, Ann Arbor, Michigan 48109, U.S.A. Salvador Moncada, M.D., Ph.D., The Wellcome Research Laboratories, Department of Prostaglandin Research, Langley Court, Beckenham, Kent, BR3 3BS, England Richard B. Moore, M.D., Department of Surgery, Medical School, University of Min• nesota, 516 Delaware Street S.E., Minneapolis, Minnesota 55455, U.S.A. Sital Moorjani, Ph.D., Centre de Recherches sur les Maladies Lipidiques, Centre Hospitalier de l'Universite Laval, 2705 boulevard Laurier, Ste-Foy, Quebec GIV 4G2, Canada Joel D. Morrisett, Ph.D., Department of Medicine, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. John A. Morrison, Ph.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Howard G. Muntz, Department of Pharmacology and Cell Biophysics, University of Cincin• nati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Thomas A. Musliner, M.D., Brown University Program in Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906, U.S.A. James Fraser Mustard, M.D., Ph.D., Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8S 4J9, Canada Nicolas Myant, M.D., F.R.C.P, MRC Lipid Metabolism Unit, Hammersmith Hospital, Ducane Road, London W12 OHS, England Haruo Nakamura, M.D., Department of Medicine, Jikei University, Aoto Hospital, 6-41-2 Aoto Katsushika, Tokyo, Japan Alberto Nasjletti, M.D., Department of Pharmacology, College of Medicine, The University of Tennessee Center for the Health Sciences, 800 Madison Avenue, Memphis, Tennes• see 38163 E.K. Neely, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Paul J. Nestel, M.D., F.R.A.C.P., Head, Cardiovascular Metabolism and Nutrition Re• search Unit, Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia 3181 W.P. Newman, III, M.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Lousiana 70112, U.S.A. Esko A. Nikkilii, M.D., Third Department of Medicine, University of Helsinki Central Hospital, 00290 Helsinki 29, Finland Fujio Numano, M.D., Department ofInternal Medicine, Tokyo Medical and Dental Univer• sity, 5-45, Yushirna l-Chome, Bunkyo-Ku, Tokyo 113, Japan Celia Oakley, M.D., F.R.C.P., Clinical Cardiology, Hammersmith Hospital, Ducane Road, London W12 OHS, England M.C. Oalman, D.P.H., Departments of Pathology, Public Health and Preventive Medicine, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A.

xxxiii Takamitsu Oikawa, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Thomas Olivecrona, M.D., Department of Medical Chemistry, University of Umea, S 901 87 Umea, Sweden Michael F. Oliver, M.D., The Duke of Edinburgh Professor of Cardiology, Department of Cardiology, University of Edinburgh Medical School, Royal Infirmary, Edinburgh EH 39YW, Scotland Anders G. Olsson M.D., King Gustaf V Research Institute, Karolinska Hospital, S 104 01 Stockholm, Sweden P. Oster, M.D., Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, D6900 Heidelberg, Federal Republic of Germany Christopher J. Packard, B.Sc., Ph.D., University Department of Biochemistry, Royal Infir• mary, Glasgow G4 OSF, Scotland A. Jean Palmer, M.B., F.R.A.C.P., Division of Preventive Cardiology, Prince Henry and Prince of Wales Hospitals, Sydney, New South Wales, Austr!lia Sharon Pangburn, Division of Metabolic Disease, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A. Rodolfo Paoletti, M.D., Centre Enrica Grossi Paoletti, Direttore, Istituto di Farmacologia e di Farmacognosia, Universita di Milano, Via A. Del Sarto, 21, 20129 Milano, Italy L.G. Petrova-Maslakova, M.D., Institute for Experimental Medicine, Academy of Medical Science U.S.S.R., Kirovsky 69171, Leningrad 197022, U.S.S.R. Ray C. Pittman, Ph.D., Division of Metabolic Disease, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A. A. Poli, M.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Farmacognosia, Universita di Milano, Via A. Del Sarto 21, 20129 Milano, Italy Craig M. Pratt, M.D., Department of Medicine, Baylor College of Medicine, Director, Exercise Laboratory, and Co-Director, Coronary Care Unit, The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. Michael Preece, M.Sc., M.D., M.R.C.P., Department of Growth and Development, Insti• tute of Child Health, 30 Guilford Street, London WC1N lEN, England Klaus Preissner, Klinisches Institute fur Herzinfarktforschung an der Medizinischen, Univer• sitatsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Margaret Forney Prescott, Ph.D., Department of Pathology, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. Giobatta Quinci, D.Chem., Regional General Hospital, Unit for Atherosclerosis, National Council for Research 30100 Venice, Italy B. Radharkrishnamurthy, Ph.D., Departments of Medicine and Biochemistry, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Elaine Raines, Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, U.S.A. Rajasekhar Ramakrishnan, Ph.D., Arteriosclerosis Research Center and Department of Pediatrics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A. Eva Ray, Ph.D., Department of Physiology and Biochemistry, The Medical College of Pennsylvania and Hospital, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, U.S.A. Catherine Reardon, B.S., Department of Biochemistry, The University of Chicago, Chicago, Illinois 60637, U.S.A. Carol T. Reed, B.A., M.S., Department of Pathology, The University of Texas Health xxxiv Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, U.S.A. J.M. Reiner, Ph.D., Department of Pathology, Albany Medical College of Union Univer• sity, 47 New Scotland Avenue, Albany, New York 12208, U.S.A. G.G. Rhoads, M.D., M.P.H., Honolulu Heart Study, Kuakini Medical Center, 347 North Kuakini Street, Honolulu, Hawaii 96817, U.S.A. Basil H. Rifkind, M.D., F.R.C.P., Project Officer, Lipid Research Clinic Program, Lipid Metabolism Branch, Division of Heart and Vascular Diseases, National Heart, Lung and Blood Institute, N ationallnstitutes of Health, Building 31, Room 4A-19, Bethesda, Maryland 20205, U.S.A. Ladislas Robert, M.D., Ph.D., Directeur de Recherche au CNRS, Laboratoire de Biochimie du Tissu Conjunctif, Institut de Recherches Universitaire sur les Maladies Vasculaires, Faculte de Medicine, Universite Paris-Val de Marne, 6, Rue du General Sarrail, 94010 Creteil, France Abel Robertson, M.D., Ph.D., Institute of Pathology, School of Medicine, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, U.S.A. W.A. Rock, M.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Russell Ross, Ph.D., Department of Pathology, SM-30, University of Washington School of Medicine, Seattle, Washington 98195, U.S.A. George Rothblat, Ph.D., Departments of Physiology and Biochemistry, The Medical Col• lege of Pennsylvania and Hospital, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, U.S.A. Richard D. Rucker, M.D., Department of Surgery, School of Medicine, University of Minnesota, 516 Delaware Street, S.E., Minneapolis, Minnesota 55455, U.S.A. David C. Sabiston, Jr., M.D., James Buchanan Duke Professor of Surgery and Chairman, Department of Surgery, Duke University Medical School, Durham, North Carolina 27710, U.S.A. Bengt Samuelsson, M.D., Department of Chemistry, Karolinska Institute, S-I04 01 Stock• holm, Sweden Ralph Sapsford, F.R.C.S., Department of Surgery, Hammersmith Hospital, Ducane Road, London W12 OHS, England Angelo M. Scanu, M.D., Department of Medicine, The University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. E.J. Schaefer, M.D., Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205, U.S.A. Hans-Eckart Schaefer, M.D., Universitiit zu Koln, Abteilung fiir Feinstrukturelle Pathologie, Pathologisches Institut, Josef-Stelzmannstrasse 9, 0-5 Koln 41, Federal RepUblic of Germany T.J. Schaffner, M.D., Department of Pathology, University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. G. Schellenberg, M.D., Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, 06900 Heidelberg, Federal Republic of Germany Gotthard Schettler, M.D., Direktor, Medizinische Universitatis Klinik, University of Heidelberg, Bergheimer Strasse 58, 06900 Heidelberg, Federal Republic of Germany Gunther Schlierf, M.D., Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, 0 6900 Heidelberg, Federal Republic of Germany James A. Schoenberger, M.D., Chairman, Department of Preventive Medicine, Rush• Presbyterian-St. Lukes Medical Center, 316 Service Building, 1753 West Congress Parkway, Chicago, Illinois 60612, U.S.A. Gustav Schonfeld, M.D., Lipid Research Center, Departments of Preventive Medicine and

xxxv Medicine, Washington University School of Medicine, Box 8046, 4566 Scott Avenue, St. Louis, Missouri 63110, U.S.A. Otto Schrecker, M.D., Klinisches Institut flir Herzinfarktforschung an der Medizinischen, Universitiitsklinik Heidelberg, Bergheimer Strasse 58, D 6900 Heidelberg, Federal Republic of Germany Colin J. Schwartz, M.D., B.S., F.R.A.C.P., Department of Pathology, The University of Texas Health Science Center, San Antonio, 7703 Boyd Curl Drive, San Antonio, Texas 78284, U.S.A. R.F. Scott, M.D., Department of Pathology, Albany Medical College of Union University, 47 New Scotland Avenue, Albany, New York 12208, U.S.A. Janet Seager, M.A., Division of Cardiology, Department of Medicine, University of California Center for the Health Sciences, Los Angeles, California 90024, U.S.A. Dietrich Seidel, M.D., Department of Clinical Chemistry, Lehrstuhl fur Klinische Chemie der Medizinischen Einrichtungen der Universitiit Gottingen, Robert-Koch-Strasse 40, 3400 Gottingen, Federal Republic of Germany Alan H. Seplowitz, M.D., Arteriosclerosis Research Center and the Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A. Ishaiahu Schechter, Ph.D., Division of Cardiology, Department of Medicine, University of California Center for the Health Sciences, Los Angeles, California 90024, U.S.A. James Shepherd, B.Sc., M.B., Ph.D., University Department of Biochemistry, Royal Infir• mary, Glasgow G4 OSF, Scotland Hiroshi Shigematsu, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Harris B. Shumacker, Jr., M.D., Distinguished Professor of Surgery Emeritus, Indiana University Medical Center, and Senior Surgical Consultant, St. Vincent Hospital and Health Care Center, 8402 Harcourt Road, Indianapolis, Indiana 46260, U.S.A. K. Silberbauer, M.D., Atherosclerosis Research Groups at the Department of Medical Physiology, University of Vienna, Vienna, Austria Judy M. Simpson, B.Sc, Department of Statistics, School of Mathematics, University of New South Wales, Kensington, New South Wales, Australia Charles F. Sing, Ph.D., Department of Human Genetics, The University of Michigan Medi• cal School, 1137 E. Catherine Street, Ann Arbor, Michigan 48109, U.S.A. H. Sinzinger, M.D., Atherosclerosis Research Group at the Department of Medical Physiol• ogy, University of Vienna, Vienna, Austria Cesare R. Sirtori, M.D., Ph.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Farmacognosia, Universita di Milano, Via A. Del Sarto 21, 20129 Milano, Italy M. Sirtori, M.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Farmacog• nosia, Universita di Milano, Via A. Del Sarto 21, 20129 Milano, Italy Joan Slack, D.M., F.R.C.P., MRC Clinical Genetics Unit, Institute of Child Health, 30 Guilford Street, London WCIN lEN, England Donald M. Small, M.D., Chief, Biophysics Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, U.S.A. Charlene Smith, R.D., Lipid Research and General Clinical Research Centers, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, U.S.A. Elspeth B. Smith, Ph.D., B.A., University of Aberdeen, Department of Chemical Pathol• ogy, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD, Scotland Frank R. Smith, M.D., Arteriosclerosis Research Center and Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, U.S.A.

xxxvi Louis C. Smith, Ph.D., Department of Medicine, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. Allen Sniderman, M.D., Edwards Professor of Cardiology, Cardiovascular Research Unit, McGill University, Royal Victoria Hospital, Montreal H3A lAl, Quebec, Canada Lilian Socorro, Ms.Sc., Laboratorio de Lipoproteinas, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Apartado 1827, Caracas-l 0 1, Ven• ezuela Lars A. Solberg, M.D., Department of Pathology, Ullevaal Hospital, Oslo 1, Norway Paul Sorlie, B.S., Biometric Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205, U.S.A. James T. Sparrow, Ph.D., Department of Medicine, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. F. Spengel, M.D., Department of Medicine, Medizinische Poliklink der Universitiit Miin• chen, Pettenkoferstrasse 8A, D-8000 Miinchen 2, Federal Republic of Germany Eugene A. Sprague, Ph.D., Department of Pathology, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, U.S.A. Sathanur R. Srinivasan, Ph. D., Department of Medicine, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Richard W. St. Clair, Ph.D., Department of Pathology and the Arteriosclerosis Research Center, Bowman Gray School of Medicine of Wake Forest University, 300 South Hawthorne Road, Winston-Salem, North Carolina, 27103, U.S.A. Herbert C. Stary, M.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Thomas E. Starzl, M.D., Ph.D., Chairman, Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, U.S.A. A. Stiehl, M.D. , Department of Medicine, University of Heidelberg, Bergheimer Strasse 58, D6900 Heidelberg, Federal Republic of Germany Evan A. Stein, M.D., Department of Medicine, Lipid Research, University of Cincinnati Medical Center, Cincinnati General Hospital, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. Olga Stein, M.D., Department of Experimental Medicine and Cancer Research, Hebrew University, Hadassah Medical School, Jerusalem, Israel Yechezkiel Stein, M.D., Chairman, Department of Medicine B, Lipid Research Laboratory, Hadassah Medical School, Jerusalem, Israel Daniel Steinberg, M.D., Head, Division of Metabolic Disease, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, U.S.A. Robert Steiner, F.F.R., F.R.C.P., Department of Diagnostic Radiology, Hammersmith Hospital, Ducane Road, London W12 OHS, England Michael B. Stemerman, M.D., Head, Thrombosis and Hemostasis Unit, Department of Medicine and The Thorndike Laboratory, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215, U.S.A. Grant N. Stemmermann, M.D., Director of Laboratories, Honolulu Heart Study, Kuakini Medical Center, 347 North Kuakini Street, Honolulu, Hawaii 96817, U.S.A. Nils H. Sternby, M.D., Chairman, Department of Pathology, University of Lund, Malmo General Hospital, S214 01 Malmo, Sweden Richard K. Stockton, Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77030, U.S.A. Wilhelm Stoffel, M.D., Ph.D., Department of Biochemistry, Institut fiir Physiolgische

xxxvii Chemie, Universitiit zu Koln, Joseph-Stelzmann-Str. 52, 5000 Koln 41, Federal Repub• lic of Germany Jack P. Strong, M.D., Chairman, Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Albert J. Sunseri, Ph.D., Chicago Heart Association, Chicago, Illinois, U.S.A. Naoki Suzuki, M.D., Department of Medicine, Jikei University, Aoto Hospital, 6-41-2 Aoto, Katsushika, Tokyo, Japan Marja-Riitta Taskinen, M.D., Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267, U.S.A. L.M. Tchichatarashvili, M.D., Institute for Experimental Medicine, Academy of Medical Science USSR, Kirovsky 69/71, Leningrad 197022 U.S.S.R. Babie Teng, M.Sc., Cardiovascular Research Unit, Royal Victoria Hospital, McGill Univer• sity, Montreal H3A lAl, Quebec, Canada Gilbert Thompson, M.D., F.R.C.P., MRC Lipid Metabolism Unit, Hammersmith Hospital, Ducane Road, London W12 OHS, England Wilbur A. Thomas, M.D., Cyrus Strong Merrill Professor and Chairman, Department of Pathology, Albany Medical College of Union University, 47 New Scotland Avenue, Albany, New York 12208, U.S.A. Matti Tikkanen, M.D., Third Department of Medicine, University of Helsinki Central Hos• pital, 00290 Helsinki 29, Finland Jack L. Titus, M.D., Ph.D., The Moody Chairman, Department of Pathology, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. V. Toca, M.S., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. R.E. Tracy, M.D., Ph.D., Department of Pathology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Elena Tremoli, Ph.D., Center Enrica Grossi Paoletti, Istituto di Farmacologia e di Far• macognosia, Universita di Milano, Via A. Del Sarto 21, 20120 Milano, Italy V.F. Tryufanov, M.D., Institute of Experimental Medicine, Academy of Medical Science USSR, Kirovsky 69171, Leningrad 197022, U.S.S.R. Thomas B. Tschopp, M.D., Department of Pharmacology Research, F. Hoffman-LaRoche and Company, 4002 Basel, Switzerland P. Tun, M.D., Cardiovascular Research Institute, University of California, San Francisco, California 94143, U.S.A. Gerd Utermann, M.D., Institute fiir Humangenetik und Genetische Poliklinik, Der Philipps Universitiit Marburg, Bahnhofstrasse 7A, 3550 Marburg an der Lahn, Federal Republic of Germany Richard L. Varco, M.D., Ph.D., Department of Surgery, School of Medicine, University of Minnesota, 516 Delaware Street SE, Minneapolis, Minnesota 55455, U.S.A. Draga Vesselinovitch, D. V .M., M. Sc., Specialized Center of Research in Atherosclerosis, Department of Pathology, University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. Ismo Virtanen, M.D., Third Department of Medicine, University of Helsinki Central Hospi• tal, Helsinki 29, Finland Arthur Vogel, M. D., Ph.D., Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, U.S.A. John C. Voyta, B.S., Department of Medicine, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. A.W. Voors, M.D., Dr.P.H., Departments of Public Health and Preventive Medicine and xxxviii Medicine, Louisiana State University Medical Center, 1542 Tulane Avenue, New Or• leans, Louisiana 70112, U.S.A. Kenneth W. Walton, M.D., D.Sc., Ph.D., F.R.C.Path., Department of Investigative Pathology, The Medical School, The University of Birmingham, Birmingham B 15 2TJ, England Patsy Wang-Iverson, Ph.D., Division of Arteriosclerosis and Metabolism, Department of Medicine, Mount Sinai Medical Center, I Gustav Levy Place, New York, New York 10029, U.S.A. Emory D. Warner, M.D., Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, U.S.A. G. Russell Warnick, M.S., Division of Metabolism and Endocrinology, Northwest Lipid Research Clinic, Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington 98104, U.S.A. L.S. Webber, Ph.D., Departments of Medicine and Biometry, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112, U.S.A. Philip Weech, Ph.D., Laboratory of Lipid and Lipoprotein Studies, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, Oklahoma 73104, U.S.A. Richard Weil, III, M.D., Department of Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, U.S.A. Donald G. Weilbaecher, M.D., Department of Pathology, Baylor College of Medicine and The Methodist Hospital, 6565 Fannin, Houston, Texas 77030, U.S.A. N. Weinstock, Ph.D., Lehrstuhl fiir Klinische Chemie der Medizinischen Einrichtungen der Universitiit Gottingen, Robert-Koch-Strasse 40, 3400 Gottingen, Federal Republic of Germany David B. Weinstein, Ph.D., Department of Medicine, M-013D, Division of Metabolic Disease, School of Medicine, University of California at San Diego, La Jolla, Califor• nia 92093, U.S.A. Richard J. West, M.D., F.R.C.P., Department of Child Health, St. George's Hospital Medical School, London, SW17 ORE, England Robert W. Wissler, M.D., Ph.D., Department of Pathology and the Specialized Center of Research in Atherosclerosis, The University of Chicago and The Pritzker School of Medicine, 950 East 59th Street, Chicago, Illinois 60637, U.S.A. G. Wolfram, M.D., Department of Medicine, Medizinische Poliklinik, Universitiit Miin• chen, Pettenkoferstrasse 8A, D-8ooo Miinchen 2, Federal Republic of Germany Joan M. Woodhill, D.Sc., Head, Division of Nutrition and Dietetics, Prince Henry and Prince of Wales Hospitals, Sydney, New South Wales, Australia Minoru Yamamoto, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan Yoshio Yamauchi, M.D., Department of Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo 160, Japan L.A. Zeech, M.D., Molecular Diseases Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205, U.S.A. Donald B. Zilversmit, M.D., Division of Nutritional Sciences and Section of Biochemistry, Molecular and Cell Biology, Division of Biological Sciences, Cornell University, Ithaca, New York 14853, U.S.A. Nepomuk Zollner, M.D., Department of Medicine, Chief, Medizinische Poliklinik, Univer• sitiit Miinchen, Pettenkoferstrasse 8A, D-80oo Miinchen 2, Federal Republic of Ger• many Yu N. Zubzhitsky, M.D., Institute of Experimental Medicine, Academy of Medical Science U.S.S.R., Kirovsky 69171, Leningrad 197022, U.S.S.R.