Development of coronary heart disease in familial hypercholesterolemia

Abstract

We studied the development of coronary heart disease in 14 homozygous and 1043 heterozygous patients with familial hypercholesterolemia (FH). Forty-three (63%) out of the deceased 68 heterozygous patients died of coronary heart disease. The mean age at death was significantly less in male heterozygotes (56 years) than in female heterozygotes (68 years). Five homozygous and 105 male and 56 female heterozygous patients received coronary angiographic evaluation. The regression equations between age (X) and coronary stenosis index (Y) obtained by assigning score (0 to 4) to each of 15 coronary artery segments were Y=1.57X−20.43 in the homozygotes, Y=0.52X−9.1 in the male heterozygotes, and Y=0.47X−12.54 in the female heterozygotes. From these data, we can assume that coronary artery stenosis detectable by angiography will occur after 17 and 25 years of age in male and female heterozygotes, respectively, and the treatment of heterozygotes with lipid-lowering drugs can be delayed until late adolescence.

A new variant of low density lipoprotein (LDL) receptor gene (FH-Tonami-2) with 10kb deletion eliminating exons 2 and 3 deleted the first and second repeats of ligand binding domain of LDL receptor. Serum cholesterol levels in FH-Tonami-2 patients were lower than those of classical FH patients. All 4 true homozygotes with FH-Tonami-2 are presently alive at ages 62, 51, 48 and 33, and the heterozygotes have also survived longer than classical FH patients. From these results, we conclude that FH-Tonami-2, caused by a partially impaired LDL receptor with small deletion in its binding domain, produces a mild type of FH.