Familial aggregation of coronary heart disease and its relation to known genetic risk factors

The question of how much of the familial aggregation of coronary heart disease is explained by familial clustering of coronary risk factors was approached by a case-control study involving 145 white male survivors of myocardial infarction, 145 age-matched white male blood donors, and the first-degree relatives of both groups. Certain risk factors such as serum cholesterol, triglyceride, and fasting blood glucose levels, blood pressure, and smoking history were determined in patients and control subjects. Relatives were interviewed. If the person was deceased, a copy of the death certificate was obtained. With the exception of high blood pressure, risk factors were significantly more frequent in patients than in control subjects.Among first-degree relatives of survivors of myocardial infarction, 16% had had a myocardial infarction, compared with 8.9% of relatives of control subjects. The frequency of coronary heart disease among first-degree relatives of patients and control subjects was 20.5 and 14.7%, respectively. To find out whether this higher frequency among relatives of patients was fully explained by the existence of known genetic risk factors among survivors of myocardial infarction, 2 approaches were taken. First, statistical analysis that eliminated the role of the various known genetic risk factors (by data stratification according to confounding risk variables and subsequent calculation of a pooled relative risk estimate according to the Mantel-Haenzel method) still indicated an approximately 2-fold (2.14) relative risk for myocardial infarction among families of survivors of myocardial infarction (and a risk of 1.71 for coronary heart disease). Similarly, another approach (Cox's life table regression analysis) confirmed that the classic risk factors could not predict familial occurrence.These results indicate that the familial aggregation of coronary heart disease is not entirely explained by the familial clustering of currently known coronary risk factors. Such familial aggregation could be caused by yet undefined genetic factors, by environmental factors common to family members, or by interaction of genetic factors with environmental agents.