Coronary atherosclerosis

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Regnstrom, J., Nilsson, J., Tornvall, P., Landou, C. and Harm-sten, A. (1992). Susceptibility to low density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 339, 1183-1186. 

O Ischemic heart disease results from an imbalance between myocardial oxygen demand and oxygen supply that is most often due to coronary atherosclerosis. Common clinical manifestations of ischemic heart disease include chronic stable angina and the acute coronary syndromes of unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. 

Coronary angiography detects the location and degree of coronary atherosclerosis and is used to evaluate the potential benefit from revascularization procedures. Stenosis of at least 70% of the diameter of at least one of the major epicardial arteries on coronary angiography is indicative of significant IHD. 

When drug therapy fails or if extensive coronary atherosclerosis is present, PCI is often performed to restore coronary blood flow, relieve symptoms, and prevent major adverse cardiac events. Patients with one or more critical coronary stenoses (i.e., greater than 70% occlusion of the coronary lumen) detected during coronary angiography may be candidates for PCI. Several catheter-based interventions maybe used during PCI, including ... 

Bruschke AV et al. The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. Circulation 1996 94 1913-1918. 

Kuivenhoven JA, Jukema JW, Zwinder-man AH, de Knijff P, McPherson R, Bruschke AV, et al. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. N Engl J Med 1998 338 86-93. 

Target genes involved in dmg response can also be involved in disease susceptibility. For example, polymorphisms of the cholesteryl ester transfer protein (CETP) are associated with both coronary atherosclerosis and response to pravastatin [22]. 

Dahlen et al. showed in their prospective analysis that Lp(a) is an independent risk factor for the clinical manifestations of coronary atherosclerosis, with a relative risk ranging from 1.6 to 3.6 (D4, D6). 

These results show that certain genotypes of apo(a) elevate Lp(a) levels more strongly than others and thereby influence the risk for future coronary atherosclerosis (K6, M29, S4, S42). 

A high serum Lp(a) concentration was also reported to be a significant risk factor for all strokes in a case-control study in Chinese patients (W20). In conjunction with the associations found between Lp(a) levels and coronary atherosclerosis in different ethnic groups, the latter study and earlier reports strongly support a universal role for Lp(a) in the development and clinical manifestations of atherosclerotic disease in general (M29, W20). 

A14. Armstrong, V. W., Cremer, P., Eberle, E., Manke, A., Schultze, F., Wieland, H., Kreuzer, H., and Seidel, D., The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Atherosclerosis (Shannon, Irel.) 62, 249-257 (1986). 

PI. Paillard, F., Guillo, P., Ruelland, A., Morin, A., Lebreton, H., Mabo, P., and Daubert, C., Lp(a) is an independent predictor of the severity of coronary atherosclerosis. Arteriosclerosis (Dallas) 10, 790a-791a (1990). 

Davies, M.J., 1996, Stabihty and instability two faces of coronary atherosclerosis. 

Nicholls SJ, Tuzcu EM, Sipahi 1, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. (2007) Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. J Amer Med Assn 297 499-508. 

Coronary atherosclerosis angina pectoris, myocardial infarction, arrhythmia Atherosclerosis of cerebral vessels cerebral infarction stroke... 

Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR. Primary prevention of acnte coronary events with lo-vastatin in men and women with average cholesterol levels resnlts of AECAPS/TexCAPS. Air Eorce/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998 279 1615-22. 

Blackburn JP, Peters NS, Yeh HI, Rothery S, Severs NJ Upregulation of connexin 43 gap junctions during early stages of human coronary atherosclerosis. Arterioscler Thromb Vase Biol 1995 15 1219-1228. 

Northcote RJ. Beta blockers, lipids, and coronary atherosclerosis fact or fiction BMJ (Clin Res Ed) 1988 296(6624) 731-2. 

Patient Population. The proband of the B family, T.B., was referred to the Lipid Research Clinic at The Johns Hopkins Hospital at the age of five years because of hypercholesterolemia of 900 mg/100 ml. She had multiple planar xanthomas that had first appeared at three years of age. The patient was free of symptoms of ischemic heart disease. The index lipoprotein pattern was type lib (57), with marked hypercholesterolemia, hyperbeta-lipoproteinemia, a mild hyperprebetalipoproteinemia and hypertriglyceridemia. None of the relatives of T.B. had xanthomas or corneal arcus one (J.S.) developed signs of premature coronary atherosclerosis at the age of 43 years. Increased total plasma and LDL cholesterol levels were transmitted over three generations on both maternal and paternal sides of the family (Fig. I). The parents of the proband, S.B. and K.B., had endogenous hypertriglyceridemia as well. Two normolipidemic members of this family (S.B., Jr. and E.B.), were also studied. 

Yutani, C., Imakita, M., Ishibashi-Ueda, H., Tsukamoto, Y., Nishida, N. and Ikeda, Y. (1999) Coronary atherosclerosis and interventions pathological sequences and restenosis. PatholInt., 49, 273-290. 

Rackley CE. Hormones and coronary atherosclerosis in women. Endocrine. 2004 24 245-250. 

In kindreds with this disorder, individuals may have elevated levels of VLDL, LDL, or both, and the pattern may change with time. Familial combined hyperlipoproteinemia involves an approximate doubling in VLDL secretion. It seems to be transmitted as a semidominant trait. Triglycerides can be increased by the factors noted above. Elevations of cholesterol and triglycerides are generally moderate, and xanthomas are usually absent. Drug treatment is warranted because the risk of coronary atherosclerosis is increased and diet alone does not normalize lipid levels. A reductase inhibitor or ezetimibe in combination with niacin is usually required to treat these patients. 

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