Coronary artery disease, premature

Familial hypercholesterolemia (FH) is an autosomal dominantly inherited disease caused by mutations in the gene for the LDL receptor. Up to now more than 680 distinct mutations, distributed over the entire gene, have been described [42]. Heterozygous FH individuals express only half the number of functional LDL-r and, therefore, have a markedly raised plasma cholesterol and usually present with premature coronary artery disease. Homozygous FH individuals are more severely affected and may succumb before the age of maturity. The prevalence of heterozygous FH is approximately 1 in 500 in Caucasians. 

It is indicated in premature infants exposed to high concentration of oxygen, correction of established vitamin E deficiency, in patients at risk of developing vitamin E deficiency, nocturnal muscle cramps, intermittent claudication, fibrocystic breast disease, coronary artery disease and as an antioxidant. 

Ordovas JM, Civeira F, Genest J, Jr et al. Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipopro-teins, and premature coronary artery disease. Atherosclerosis. 1991, 87 75-86. 

Genest JJ Jr, et al. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol 1990 ... 

Sudhir K, Chou TM, Chatterjee K, Smith EP, Williams TC, Kane JP, Malloy M J, Korach KS, Rubanyi GM. Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man. Circulation 1997 96(10) 3774-3777. 

Schaefer, E. J., Heaton, W. H., Wetzel, M. G., and Brewer, H. B., Jr., Plasma apolipoprotein A-I absence associated with a marked reduction of high density lipoproteins and premature coronary artery disease. Arteriosclerosis 2, 16-26 (1982). 

The abuse of tobacco is the single most important risk factor for cancer and several other diseases. It contributes to about one-third of cancer cases, one-fourth of coronary artery disease, and an estimated 400,000 premature deaths each year in the United States (D10, P14). Smoking is a major risk factor not only for lung cancer, but for mouth, larynx, kidney, urinary bladder, esophagus, stomach, and pancreas cancers (A8). 

Of the many disorders of lipoprotein metabolism (Tables 5.2 and 5.3), familial hypercholesterolaemia type II may be the most prevalent in the general population. It is an autosomal dominant disorder that results from mutations affecting the structure and function of the ceU-surface receptor that binds plasma LDLs and removes them from the circulation. The defects in LDL-receptor interaction result in lifelong elevation of LDL cholesterol in the blood. The resultant hypercholesterolaemia leads to premature coronary artery disease and atherosclerotic plaque formation. Familial hypercholesterolaemia was the first inherited disorder recognised as being a cause of myocardial infarction (heart attack). 

Increase in LDL levels no effect on HDL, VLDL or plasma triglyceride levels significant cause of hypercholesterolemia and premature coronary artery disease Decreased levels of plasma cholesteryl esters and lysolecithin abnormal LDLs (Lp-X) and VLDLs symptoms also found associated with cholestasis... 

J. J. Genest Jr., S. S. Martin-Munley, J. R. McNamara, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 85, 2025 (1992). 

Sveger T, Flodmark CE, Nordborg K, et al. Hereditary dyslipidaemias and combined risk factors in children with a family history of premature coronary artery disease. Arch Dis Child 2000 82 292-296. 

Indeed, 27-hydroxycholesterol is a prominent oxysterol found in lesions. Rare patients lacking 27-hydroxylase activity have xanthomas and premature coronary artery disease, and some studies have shown an inverse correlation between 27-hydroxylase levels and atherosclerosis in subjects without enzyme deficiency per se (N.R. Cary, 2001). However, 27-hydroxylase-deficient mice on a non-atherogenic background or diet do not develop xanthomas or spontaneous atherosclerotic lesions (E. Leitersdorf, 1998). 

In addition to diabetes mellitus, Mr. Applebod has a hyperlipidemia (high blood lipid level—elevated cholesterol and triacylglycerols), another risk factor for cardiovascular disease. A genetic basis for Mr. Applebod s disorder is inferred from a positive family history of hypercholesterolemia and premature coronary artery disease in a brother. 

Hyperlipidemia is known to be one of the most potent factor associated with the premature development of atheromatous arterial disease. Thus an increased serum cholesterol level is frequently found in patients with ischemic heart disease and myocardial infarction, and hypercholesterolemic patients have a high incidence of coronary artery disease. Therefore, because cholesterol is partially eliminated from the body as bile acids (see Section VB), it would be important to know the role of bile acid metabolism in the development of different types of hypercholesterolemia. 

Among certain athletes, the misuse of anabolic steroids to build muscle mass and strength, particularly for sports that require explosive action, is common. The risks associated with abusing anabolic steroids for this purpose are enormous heightened aggressiveness, sterility, impotence, and premature death from complications of diabetes, coronary artery disease, and liver cancer. 

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