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

Abstract 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 which age is taken into consideration; in these two age groups women have significantly higher cholesterol levels than men. Again it was found that the values for men and women are fairly close, differing at the 5 per cent level for only two age groups, 58 to 62 and 63 to 67. Keys and associates published serum cholesterol values which are expected to be exceeded by only 5 per cent of the population in each age group. The frequency of hypercholesteremia for the total usable sample, according to this method of analysis, was 12.0 per cent; the frequency among the siblings of the hypercholesteremic probands was 36.2 per cent and among the children 34.0 per cent. These frequencies, again, are significantly greater than those found for the index patients; but are not significantly different from the corresponding values obtained when levels of cholesterol above 279 mg. per 100 ml. were considered to represent hypercholesteremia. Of the 478 probands 266 were Jewish and 212 were non-Jewish. Hypercholesteremia was significantly more frequent among the Jewish probands (21 per cent versus 9 per cent), but the frequency among siblings and children was not different when Jewish hypercholesteremic probands and families were compared with non-Jewish. The mode of inheritance of idiopathic hypercholesteremia remains to be worked out. The finding that hypercholesteremia is as frequent among the siblings and children of the non-Jewish hypercholesteremic probands as compared with the Jewish may indicate that environmental factors are not of too great importance in determining the presence of hypercholesteremia. The validity of these tentative conclusions awaits the completion of a study now being done in a more representative and complete population group. However, even these preliminary observations shed some light on the complicated error of metabolism involved in hypercholesteremia and predisposition to early atherosclerosis.