Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene mutation
Ferrières, J.; Lambert, J.; Lussier-Cacan, S.; Davignon, J.
Circulation 92(3): 290-295
1995
ISSN/ISBN: 0009-7322 PMID: 7634440 Document Number: 452971
Background: Familial hypercholesterolemia (FH), an autosomal codominant disease, is characterized by high levels of LDL cholesterol and a high incidence of coronary artery disease (CAD). To date, genetic heterogeneity has hindered the proper assessment of the relation between risk factors and CAD in FH patients. Methods and Results: We studied the association between CAD and common risk factors in a sample of 263 French Canadian FH patients (147 women, 116 men) carrying the same gt 10-kb deletion 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 performed to test the association between CAD and age, tendon xanthomas, cigarette smoking, hypertension, diabetes mellitus, apolipoprotein E polymorphism, total plasma cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, and lipoprotein(a) (Lp(a)). In FH women, significant multivariate predictors were age (odds ratio, 1.10 for 1 year; P lt .0001), VLDL cholesterol (odds ratio, 3.85 for 1 natural log unit; P lt .002), and LDL cholesterol (odds ratio, 1.42 for 1 mmol/L; P lt .02). In FH men, age (odds ratio, 1.08 for 1 year; P lt .0001) and HDL cholesterol (odds ratio, 0.14 for 1 mmol/L; P=.05) were significant predictors of disease. Lp(a) was not a significant predictor in univariate or multivariate analyses. Conclusions: This study suggests that increased risk of CAD in FH is not solely due to elevated LDL cholesterol levels and demonstrates a sex-specific lipoprotein influence on CAD in a large sample of FH patients carrying the same LDL receptor gene defect.