This volume is a collection of the most significant contributions to the 4th International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE: STRATEGIES OF PREVENTION OF CORONARY HEART DISEASE, CARDIAC F AlLURE, AND STROKE held in Washington, D. C. in April 1997. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological, clinical, and biological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of populations in the industrialized countries. The evidence that a combination of risk factors confers a very high risk of developing cardiovascular diseases, is of pivotal interest in the process of detection of patients who will benefit the most from pharmacological treatment. Many recent epidemiological data identifying the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline atherosclerosis as a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure rheologic forces, carbohydrate tolerance, and thrombogenic factors, including fibrinogen, tissue factor, PAl-I, and homocysteine. Furthennore, the risk associated with anyone of these risk factors varies widely depending on the level of the associated atherogenic risk factors. Hyper cholesterolemia and hypertriglyceridemia, for instance, are more common than would be expected by chance among hypertensive patients.

A great deal of experimental, clinical and epidemiological data have been gathered to confirm the strict and causal correlation between plasma lipoproteins and coronary heart disease. However, as usually happens in research, many more interesting issues are being studied, opening new fields of research for the future. These new advances, together with the combined efforts of cell biologists and lipoprotein chemists, have set the pace for an exciting period of research and clinical applications of diets and drugs affecting plasma and cell lipids. This volume, which includes the work of many of the leading world labortories, represents an authoritative and up-to-date appraisal of the status of the art and a stimulus to future research at the laboratory and clinical level in a fascinating area of clinical and preventive medicine.

This book includes the most significant contributions of the 3rd International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE held in Florence, Italy, July 6-9, 1994. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of the general population. The evidence that in high risk patients, a combination of risk factors often is detected, is highlighted in these Proceedings. Many recent epidemiological data identifYing the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline how atherosclerosis is a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.

Interest in the field of atherosclerosis research has broadened in recent years. However the main focus remains on the physiopathology of the arterial wall and on its interaction with blood constituents. The purpose of this NATO Advanced Study Institute on "Factors in Formation and Regression of the Atherosclerotic Plaque" was to discuss the following points: a) The physiopathology of the arterial wall; b) Animal models; c) Methods of studying the progression and regression of atherosclerotic lesions quantitatively; d) The role of lipoproteins, platelets, smoke, alcohol, etc. in the formation of atherosclerotic lesions; e) The pharmacological and dietary control of "risk factors." This volume is a collection of the most relevant presentations on these topics. We hope it will provide a background for young scientists as well as a stimulus for further research to biologists and clinicians. We wish to acknowledge the support of NATO and the Nutrition Foundation of Italy in organizing this Advanced Study Institute.

Even a brief scan of the table of contents of the present volume is enough to disclose the diversity of research interests and opinions in the field of lipidology. It is precisely this diversity that is the strength of our field and that was showcased by the XII International Symposium of DRUGS AFFECTING LIPID METABOLISM (DALM). The papers published here from these proceedings may be divided into three categories: those that define-and refine---our understanding ofthe clinical benefit of aggressive lipid management, those that develop our knowledge of ris!. assessment, and those that discuss the genetic, bio~hemical, and biophysical mechanisms underlying the pathology of coronary heart disease. On the clinical front, further analysis of the results of the Scandinavian Simvastatin Survival Study (4S) has indicated the cost-effectiveness of therapy in patients with established coronary heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS), whose methodology was described at the DALM XII symposium, has demonstrated in a mostly primary-prevention population what 4S demonstrated for secondary prevention the year before: aggressive lipid-regulating therapy reduces coronary heart disease morbidity and mortality rates without concurrently increasing mortality from noncardiovascular causes. In the future, important considerations will be to develop protocols that maximize benefit in groups underrepresented in traditional clinical research for example, women and the elderly-and to improve compliance to existing treatment regimens. Furthermore, antioxidant, omega-3 fatty acid, and gene therapies warrant further investigation.

Peroxisome Proliferator Activated Receptors (PPARs) attract great attention in light of the wide spectrum of genes of biological and medical relevance identified as under their control. As a consequence, our knowledge of the role of these receptors in physiology and pathology continues to grow at a fast pace and PPARs have become an interesting target for the treatment of many pathological conditions, including diabetes and atherosclerosis. This volume provides an authoritative view of the current clinical and scientific developments within this evolving area of study.

Peroxisome Proliferator Activated Receptors (PPARs) attract great attention in light of the wide spectrum of genes of biological and medical relevance identified as under their control. As a consequence, our knowledge of the role of these receptors in physiology and pathology continues to grow at a fast pace and PPARs have become an interesting target for the treatment of many pathological conditions, including diabetes and atherosclerosis. This volume provides an authoritative view of the current clinical and scientific developments within this evolving area of study.

The issue of interaction of risk factors in cardiovascular disease is timely and of clinical relevance. This book is a collection of the scientific contributions to the 4th International Symposium on Multiple Risk Factors and Cardiovascular Disease: Strategies of Prevention of Coronary Heart Disease, Cardiac Failure, and Stroke, and addresses the role of simultaneous risk factors in patients. Because patients with two or more risk factors are at very high risk for developing cardiovascular diseases, special care should be taken in the choice of appropriate therapeutic intervention.

Risk factors are also discussed from the point of view of the biochemist and the pharmacologist by addressing the mechanisms underlying the onset of hypertension, hyperlipoproteinemia, hypercoagulability, and the possibility of therapeutic intervention.

This book will therefore be of value to the biochemist, pharmacologist, and clinical pharmacologist, as well as to specialists in the field of cardiovascular medicine in order to keep up-to-date with current knowledge in this fast moving field of research.

Patients with two or more risk factors have a very high risk of developing cardiovascular disease. It follows that the strategy for the intervention of multiple risk factors is in fact of paramount relevance in detecting patients at high risk of cardiovascular disease requiring therapeutic intervention. The text also discusses risk factors from the point of view of biochemists and pharmacologists by addressing the mechanisms underlying the onset of hypertension, hyperlipoproteinaemia, hypercoagulability and the possibility of therapeutic intervention.