Genetic and environmental factors affecting the incidence of coronary artery disease in heterozygous familial hypercholesterolemia.

This study explores the influence of selected genetic and environmental factors on the clinical expression of heterozygous familial hypercholesterolemia (FH). A detailed examination of the physical and biochemical features of FH was performed in a large cohort of 208 females and 156 males. Females with FH had higher levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol when compared with males, although the concentration of HDL cholesterol was significantly lower for both sexes when compared with normals. The reported incidence of coronary artery disease (CAD) was 31% for men and 13% for women, which was lower when compared with figures from previous studies. The average age of onset of coronary symptoms was delayed in females, with a mean age of 55 years compared with 48 years for males (p less than 0.05). A greater risk of developing CAD in men was associated with lower levels of HDL cholesterol and a history of smoking. In women, however, CAD was associated with elevated triglycerides and the presence of hypertension. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles of apolipoprotein E in 125 unrelated FH subjects did not differ significantly from the normal population. In addition, there was no apparent relation between apo E4 and the concentration of any of the parameters in the plasma lipid profile; however, the presence of the E2 isoform was associated with significantly elevated triglycerides in both sexes. This study has allowed us to identify those factors, which, in addition to total cholesterol levels, are associated with the development of premature coronary atherosclerosis in heterozygous FH.