Hypercholesterolemia [antikvár]

Foreword In recent years, the case against plasma lipoproteins as inciting agents in atherosclerosis has been established beyond reasonable doubt. The evidence comes from three sources: epidemiologic correlations, animal experiments, and studies of human genetic disease. All of this evidence points to low-density lipoproteins (LDLs) as a major factor in arterial disease. Based on this indictment, consensus panels in the United States and Europe have concluded that plasma cholesterol levels greater than 240 mg/dl are dangerous, and that levels below 200 mg/dl are desirable. Large segments of the populations in Europe and the United States have cholesterol levels above these ranges, and these people are considered to be at risk for developing atherosclerosis. As the evidence against plasma lipoproteins was mounting, scientists were also learning about the normal functions of these particles. We know that lipoproteins are synthesized in liver and intestine to transport cholesterol and trigylcerides to peripheral tissues, and to return cholesterol from peripheral tissues to the liver. The concentration of plasma lipoproteins is determined by a balance between secretion and removal. Secretion is dictated by the metabolic state of the individual. When large amounts of lipid must be transported, large amounts of lipoproteins are produced. Lipoproteins are removed from plasma primarily by receptors on the surfaces of body cells. These receptors bind lipoproteins and carry them into cells by receptor-mediated endocytosis. The receptors are highly specific and efficient. When they function optimally, they keep the plasma lipoprotein level low even when secretion is brisk. When the receptors are diminished, plasma lipoprotein levels rise. The causes of high blood cholesterol levels are diverse. Some individuals have single-gene defects that cause cholesterol levels to rise. The prime example is familial hypercholesterolemia, which is attributable to defects in the receptor that removes LDL from blood. This disease affects 1 out of 500 individuals in most populations. Other single-gene causes include familial combined hypercholesterolemia, which is common, and familial dysbetalipoproteinemia, which is rare. The latter disease is caused by genetic defects in one of the plasma apolipoproteins, apo E, that abolish its binding to LDL receptors. In aggregate, these single-gene diseases account for only a small fraction of the individuals in the population with cholesterol levels greater than 240 mg/dl. The majority owe their high cholesterol levels to two factors: (a) a diet that is rich in saturated fatty acids and cholesterol, and (b) a set of genes that renders them susceptible to hypercholesterolemia when they eat such a diet. High fat diets raise plasma LDL levels by several mechanisms, one of which is a suppression of LDL receptors