Genetic studies on hypercholesteremia: Frequency in a hospital population and in families of hypercholesteremic index patients

Hypercholesteremia appears to be a common denominator for most patients with early coronary atherosclerosis. The frequency of the occurrence of this disorder and its possible genetic relationship become, therefore, important points in any studies designed to further our knowledge of coronary artery disease, particularly that occurring in the younger age groups. This report summarizes studies of hypercholesteremia in 250 men and 250 women, consecutive admissions to the Mount Sinai Hospital, New York, and an analysis of families of fifty-nine of the seventy-five probands who were found to have idiopathic hypercholesteremia. Serum cholesterol determinations were performed by the method of Schoenheimer and Sperry on blood drawn from patients who had fasted 12 hours. Hypercholesteremia was considered to be present if the serum cholesterol was 280 mg. per 100 ml. or greater. The age of the 250 men in the index group averaged 50.9 years, and their serum cholesterol averaged 215 mg. per 100 ml. The 250 women averaged 48.1 years, and their cholesterol 230 mg. per 100 ml. Ninetyseven of these 500 probands (41 men and 56 women) were hypercholesteremic. This group averaged 52.8 years of age, and 348 mg. per 100 ml. of serum cholesterol. Twenty-two of these ninety-seven patients were suffering from diseases associated with hypercholesteremia and were excluded from further consideration. Of the remaining 478 probands thirty-two of the 242 men (13.2 per cent) and forty-three of the 236 women (18.2 per cent) were hypercholesteremic. The frequency of hypercholesteremia was not significantly different between the two sexes. A thorough attempt was then made to examine the immediate relatives of the seventy-five hypercholesteremic probands. No relatives of sixteen of these patients could be examined. This was usually due to the fact that there was no living family member, or that those living were scattered throughout the world and therefore unavailable. Ninety-seven siblings and 110 children of the remaining fifty-nine hypercholesteremic probands were examined. The frequency of hypercholesteremia among the siblings was 51.5 per cent and among the children 29.4 per cent. Both these frequencies are significantly higher than those found among the 478 patients. Since the definition of hypercholesteremia used in the preceding calculations did not take into account the fact that serum cholesterol varies with age, the analyses were repeated using data of Keys and associates 11a in