Association With Coronary Heart Disease

The clinical significance of lipids is primarily associated with coronary heart disease (CHD) and various lipoprotein disorders. 

Increased cholesterol is a factor in the cause of atherosclerotic diseases (see also Chapter 44). As early as 1910, Windaus described cholesterol in the lesions of diseased arteries. Subsequently, many studies have confirmed that free and esterified cholesterol accumulates in the aorta, coronary arteries, and cerebral vessels, and that the rate of accumulation varies among individuals. The association between serum cholesterol and atherosclerosis in humans was first suggested in 1938, when Muller and Thanhauser each demonstrated familial aggregation of hypercholesterolemia 

TABLE 26-i 1 Serum Apo A-I Cbhccritratidhs in Persons Ages . Percentiles, U.S., 1988-9 Years by S ex and Age Means and Selected  

Modified fi om Bachorik PS, Lovejoy KL, Carroil MD, Johnson CL. Apoiipoprotein B and AI distributions in the United States. 1988-1991 results of the National Health and Nutrition Examination Survey III (NHANES III). Clin Chem 1997 43 2364-78. 

In the early 1970s, Alaupovic suggested that apoUpopro-teins should also be considered when evaluating the contribution of lipids and lipoproteins to the development of atherosclerotic disease. Several studies demonstrated that in people with CHD, changes in the serum concentrations of apo A I and apo B-lOO are similar to those for HDL and LDL, respectively. Apo B-lOO values were increased and apo A-I values were decreased in people with CHD compared with those without disease. In most studies, apo A-I and apo B-lOO were somewhat better discriminators of people with CHD than the cholesterol concentration of the corresponding lipoprotein, at least in univariate analyses. Further- 

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Familial hypertriacylglycerolemia (type IV) Overproduction of VLDL often associated with glucose intolerance and hyperinsulinemia. Cholesterol levels rise with the VLDL concentration. LDL and HDL tend to be subnormal. This type of pattern is commonly associated with coronary heart disease, type II diabetes mellitus, obesity, alcoholism, and administration of progestational hormones. 

Particulate matter Eye and nasal irritation, long-term exposure associated with coronary heart disease and lung cancer... 

Hence, it appears that hormone replacement can play a role in modifying certain risk factors associated with coronary heart disease in postmenopausal women, but the actual outcomes (heart attack, death) do not seem to be affected significantly by these hormonal interventions. Clearly, continued research in this area is needed to clarify if hormone replacement therapy can help decrease cardiac morbidity and mortality in certain postmenopausal women.60,121... 

Vendrell J, Fernandez-Real J-M, Gutierrez C, Zamora A, Simon I, Bardaji A, Ricart W, Richart C. A polymorphism in the promoter of the tumor necrosis factor-a gene (-308) is associated with coronary heart disease in type 2 diabetic patients. Atherosclerosis. 2003, 167 257-264. 

For many years, much attention has been focused on certain lipids and the lipoproteins that transport them in the circulation, mainly because of their strong association with coronary heart disease (CHD). Therefore the use of the term lipids in chnical chemistry and laboratory medicine has become virtually synonymous with lipoprotein metabolism... 

Figure 26-18 Exogenous lipoprotein metabolism pathway. TG, Triglyceride CE, cholesterol ester FC, free cholesterol Ft, phospholipids HDL, hIgh-density lipoproteins FA, fatty acid LPL, lipoprotein lipase 6, apolipoprotein B-48 A, apolipoprotein A-i C, apolipoprotein C-ll , apolipoprotein E. (From Rifai N. Lipoproteins and apolipoproteins Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 10 694-701. Copyright 1986, American Medical Association.)...

Rifai N. Lipoproteins and apolipoproteins. Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 110 ... 

It has been shown that a thermolabile form of MTHFR is a major cause of mildly elevated plasma homocysteine levels, which have been associated with coronary heart disease. The thermolabile MTHFR gene has a... 

Lacquemant, C., Lepretre, R, Pineda Torra, I., Manraj, M., Charpentier, G., Ruiz, J., Staels, B., and Froguel, P. (2000). Mutation screening of the PPARalpha gene in type 2 diabetes associated with coronary heart disease. Diabetes Metab 26, 393-401. 

Figure 6 Antiendothelial antibodies associated with coronary heart disease. Human umbilical vein endothelial cell proteins were separated by SDS-PAGE and transferred electrophoretic-ally onto nitrocellulose membranes that were then probed with human serum samples. (A) Coronary heart disease patient with several endothelial antigens, (B) serum reactive with only the 57.5 and 56 kDa doublet, and (C) normal serum showing no bands of reactivity. (Reproduced with permission from Dunn etal. (1983) Antiendothelial antibodies associated with coronary heart disease. Lancet 339 1566-1570.)...

Lp(a), identified initially as an antigenic component in a subclass of LDL (Berg, 1963) is genetically controlled and has a significant association with coronary heart disease (Berg et al., 1974). The molecular basis for its antigenic behavior is not known. 

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