Coronary heart disease, genetic factor

Hypertension is one of the two principal risk factors of many cardiovascular diseases, such as coronary heart disease (CHD), stroke, and CHF. Individuals are considered hypertensive if their systoHc arterial blood pressure is over 140 mm Hg (18.7 Pa) or their diastoHc arterial blood pressure is over 90 mm Hg (12 Pa). Over 60 million people, or one-third of the adult population in the United States are estimated to be hypertensive (163). About 90% of these patients are classified as primary or essential hypertensive because the etiology of their hypertension is unknown. It is generally agreed that there is a very strong genetic or hereditary component to this disease. 

The role of Lp(a) as a primary genetic risk factor for coronary heart disease, therefore, seems firmly established. However, in blacks, despite mean Lp(a) levels twice as high as in whites, the incidence of cardiovascular disease is apparently identical (G37, S40). The role of Lp(a) in atherosclerotic vascular disease in blacks therefore remains to be established. 

The risk from an elevated Lp(a) level is certainly not restricted to the general population. Seventy percent of the variation in Lp(a) concentrations can be accounted for by genetic factors accordingly, parental history of premature coronary heart disease is linked to elevated Lp(a) levels (D16, U7). 

The Genetic Analysis of Common Diseases Applications to Predictive Factors in Coronary Heart Disease, Sing, C. and Skolnick, M. (eds), Alan Liss, in press. 

Wang GQ, DiPietro M, Roeder K et al. Cladistic analysis of human apolipoprotein a4 polymorphisms in relation to quantitative plasma lipid risk factors of coronary heart disease. Ann Hum Genet. 2003, 67 107-124. 

Some of the variables which have been found to relate to development of various disease states are age, sex, genetic factors, developmental stage, existing disease states, personal habits, occupation, and environment. A number of studies have tried to link these factors with the development of key diseases of interest such as cancer, coronary heart disease, liver or kidney disease, the major killers of adults in the United States. 

Epidemiological studies have identified risk factors for coronary heart disease (CHD) and its underlying pathology atherosclerosis. Genetic and environmental factors interact to shape an individual s age-related risk of atherosclerosis (1,2). In the Framingham Heart Study, substantial proportion of the variability in carotid intima-media thickness (IMT) is explained by genetic factors (3). The role of gene polymorphism has been reviewed in ref. 4. 

Some 10-25% of the population have a genetic predisposition to hyperhomocysteinemia, which is a risk factor for atherosclerosis and coronary heart disease, as a result of polymorphisms in the gene for methylenetetrahydrofolate reductase. There is no evidence that supplements of vitamin Bg reduce fasting plasma homocysteine in these subjects, and like the tryptophan load test, the methionine load test may be an appropriate index of status in controlled depletion/repletion studies to determine vitamin Bg requirements, but not in population studies. 

Lipoprotein disorders are detected by measuring lipids in serum after a 10-hour fast. Risk of heart disease increases with concentrations of the atherogenic lipoproteins, is inversely related to levels of HDL, and is modified by other risk factors (Table 35-1). Evidence from clinical trials suggests that LDL cholesterol levels of 60 mg/dL may be optimal for patients with coronary disease. Ideally, triglycerides should be below 120 mg/dL. Differentiation of the disorders requires identification of the lipoproteins involved (Table 35-2). Diagnosis of a primary disorder usually requires further clinical and genetic data as well as ruling out secondary hyperlipidemias (Table 35-3). 

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