CORONARY-ARTERY DISEASE IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIAPATIENTS WITH THE SAME LDL RECEPTOR GENE MUTATION

Background Familial hypercholesterolemia (FH), an autosomal codominant disease, is characterized by high levels of LDL cholesterol and a hig h incidence of coronary artery disease (CAD). To date, genetic heterog eneity has hindered the proper assessment of the relation between risk factors and CAD in FH patients.Methods and Results We studied the ass ociation between CAD and common risk factors in a sample of 263 French Canadian FH patients (147 women, 116 men) carrying the same >10-kb de letion of the LDL receptor gene. Thirty-five women and 54 men had CAD. The mean age of onset of CAD was 45.6+/-12.7 years in women and 38.8/-9.4 years in men. Multiple logistic regression analyses were perform ed to test the association between CAD and age, tendon xanthomas, ciga rette smoking, hypertension, diabetes mellitus, apolipoprotein E polym orphism, total plasma cholesterol, triglycerides, VLDL cholesterol, LD L cholesterol, HDL cholesterol, and lipoprotein(a) [Lp(a)]. In FH wome n, significant multivariate predictors were age (odds ratio, 1.10 for 1 year; P<.0001), VLDL cholesterol (odds ratio, 3.85 for 1 natural log unit; P<.002), and LDL cholesterol (odds ratio, 1.42 for 1 mmol/L; P< .02). In FH men, age (odds ratio, 1.08 for 1 year; P<.0001) and HDL ch olesterol (odds ratio, 0.14 for 1 mmol/L; P=.05) were significant pred ictors of disease. Lp(a) was not a significant predictor in univariate or multivariate analyses. Conclusions This study suggests that increa sed risk of CAD in FH is not solely due to elevated LDL cholesterol le vels and demonstrates a sex-specific lipoprotein influence on CAD in a large sample of FH patients carrying the same LDL receptor gene defec t.