LIPOPROTEINS AND ATHEROGENESIS

ATHEROGENESIS IS MULTIFACTORIAL The development of fibrocalcific atherosclerotic plaque in human arteries is not inevitable. Most preindustrial societies have not encountered atherosclerotic cardiovascular disease. Only in the most affluent individuals are the clinical sequelae of atherogenesis evident. The existence of atherosclerosis was described more than 4000 years ago in ancient Egypt?' Examination of Egyptian mummies reveals that coronary atherosclerosis and myocardial infarction occurred in af- fluent persons.94 As affluence has increased in industrialized societies, the inci- dence of cardiovascular disease has also increased. From 1900 to 1950, the incidence of cardiovascular disease increased nearly twofold within the United States. This epidemic of the twentieth century in the United States seems to be spreading worldwide. In a recent study by the World Health Organization, cardiovascular disease led the causes of death worldwide.6y When combined, cardiovascular and cerebrovascular causes represented more than 20% of 50.5 million deaths in 1992. Thus, the trend observed in the United States earlier in this century will be reproduced worldwide in the twenty-first century. As is true for diabetes mellitus, obesity, and hypertension, atherogenesis reflects the interaction of a myriad of genetic and environmental factors. Genetic traits that are likely to enhance survival in times of famine may be deleterious in the context of affluence. It has been suggested that atherogenesis reflects a mismatch between Paleolithic genes in contemporary man. These genetic traits are particularly likely to influence energy metabolism and transport. Both genes and the environment modulate plasma lipoproteins. This energy transport system has been optimized to transfer energy-rich fatty acids in the core of lipoprotein particles to tissues either utilizing or storing energy as fat. As outlined in the article on lipoprotein physiology by Ginsberg on p. 503 of tDeceased; formerly from the Section of Cell Biology, Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland