Heterozygous familial hypercholesterolemia: Relationship between plasma lipids, lipoproteins, clinical manifestations and ischaemic heart disease in men and women

Abstract

A large cohort of 264 men and 311 women with heterozygous familial hypercholesterolemia (FH) is analysed for the presence of xanthomas, ischaemic heart disease (IHD) and plasma lipids and lipoproteins. The plasma and low density lipoprotein (LDL) cholesterol are elevated to the same extent in both sexes, but on the contrary high density lipoprotein (HDL) cholesterol is decreased in both sexes as compared to normal controls. Thus an increase in LDL and a decrease in HDL may account for the early development of IHD in both men and women with FH. Although tendon xanthomas are equally observed in both sexes, IHD is not only precocious in men but its prevalence is also higher in men as compared to women. IHD is also more severe in men as seen from the higher incidence of myocardial infarction and fatal events. Plasma triglyceride levels are significantly higher in men, but they do not account for the higher prevalence of IHD in men, since the incidence of IHD is lower in men with type IIb hyperlipoproteinemia as compared to Ila. HDL-cholesterol is significantly lower in men as compared to women with FH and therefore it may explain the differences in IHD between men and women. Irrespective of sex, the presence of tendinous xanthomas is related to elevated levels of both plasma and LDL cholesterol and higher LDL/HDL cholesterol ratio. The women with tendinous xanthomas, whether with or without IHD have similar levels of plasma lipids and lipoprotein cholesterol as compared to men with similar clinical manifestations. Although no significant differences are noted in the plasma lipid and lipoprotein levels between men either with or without IHD; in women, the occurrence of IHD is related to lower concentration of HDL-cholesterol which is not only similar to that in men with IHD, but is also significantly lower than the level observed in women with tendinous xanthomas but no IHD. These findings lead us to suggest that lower prevalence of IHD in women with FH in due to their higher concentration of HDL-cholesterol.