Ischaemic disease in men and women with familial hypercholesterolaemia and xanthomatosis. A comparative study of genetic and environmental factors in 274 heterozygous cases.

The incidence of ischaemic diseases in familial hypercholesterolaemia and xanthomatosis (familial Type II) was studied in a group of 158 men and 116 women. (1) Men and women did not differ with regard to the inherited metabolic disease. Levels of serum cholesterol, the marker of the genetic defect, were not statistically different, and cholesterol deposition in tissues, visualized by skin tendon xanthomas, was not sex related. (2) Men and women were different with regard to ischaemic diseases. The incidence was much lower in women, and the mean age of onset 9 years later. Moreover, there was a sex difference in the nature of the ischaemic disease, with a high male predominance of myocardial infarction. (3) Since the major risk factor hypercholesterolaemia could not explain such a difference, the role of other risk factors was investigated. It was shown that the incidence of ischaemic diseases was increased in women by cigarette smoking and hypertension, and that the difference in age of onset between males and females was no longer seen in smoking women. It is suggested that the genetic factor is responsible for the atherosclerotic lesion in both sexes and that other factors playing a role in ischaemic complications including tobacco and hypertension may explain the difference between men and women.