CHARACTERISTICS OF CORONARY-ARTERY DISEASE AND LIPOPROTEIN ABNORMALITIES IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA ASSOCIATED WITH DIABETES-MELLITUS OR IMPAIRED GLUCOSE-TOLERANCE

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influen ce of abnormal glucose metabolism on the development of coronary arter y disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozy gous FH who were accompanied by diabetes mellitus (DM) or impaired glu cose tolerance (IGT). The subjects of the present study were 150 patie nts with heterozygous FH, all over 40 years of age. Oral glucose toler ance tests demonstrated that 15 patients had DM and 27 had IGT. The co mbination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:4 3%). Furthermore, the prevalence of the stenoses in the distal coronar y arteries was significantly higher in the DM group than in the N grou p, while there was no significant difference in the prevalence of prox imal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM vers us N group; P < 0.01, IGT versus N group), while total cholesterol lev els were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appear ance, which implies an increase in remnant lipoproteins, was significa ntly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87 :72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). U ltracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups co mpared with the N group. These data suggest that abnormal glucose meta bolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high conce ntration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis. (C) 1997 Elsevier Science Ireland Ltd.