Coronary heart disease: genetic aspects

Morbidity and mortality differences between populations, between ethnic groups and between individuals are not satisfactorily explained by the variation of risk factors. Differences in genetic susceptibility might be responsible for a part of the unexplained variation of coronary heart disease (CHD) rates. Genetic factors are also significant in determining the level of risk factors in individuals. Ample evidence links genetic factors to the levels of serum cholesterol, blood pressure and diabetes. Marked sex differences in CHD mortality also indicate the role of heredity in the development of the disease. The male:female ratio varies widely between different countries, as well as between different ethnic groups. These variations are difficult to explain by variation in environmental and behavioral differences between males and females alone. The degree of atherosclerosis in males and females varies, depending on the anatomic location of the atherosclerosis. Inherited disorders of metabolism and the variability of anatomic patterns provide additional indications of the role of genetics. The data accumulated in the Israeli Ischemic Heart Disease Study over 15 years reveal an ethnic variation of risk factors coupled with remarkably larger variation in disease rates. Patterns of incidence assessed in the national mortality data of the Israeli study and in histologic findings in the coronary arteries of infants from different ethnic groups are compatible with a hypothesis that ethnic and sex differences in early structural changes of the coronary arteries partly determine the susceptibility of the latter to the development of atherosclerosis. In conclusion, findings from our studies and the review of the evidence from genetic epidemiologic investigations indicate a significant role of genetics in determining the degree, time course and severity of the atherosclerotic process and of the occurrence of symptomatic CHD. This important role of the genetic component is relevant to preventive strategies offered as tools for reducing the burden of CHD. Research into genetic determinants of both susceptibility to atherosclerosis or clinical manifestation of CHD and individual response to preventive measures should be encouraged.