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Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene
J Ferrières1, J Lambert, S Lussier-Cacan
1Département de médecine sociale et préventive, Faculté de Médecine, Université de Montréal, Quebec, Canada.
Insights
Familial hypercholesterolemia (FH) patients with a specific LDL receptor gene defect show varied coronary artery disease (CAD) risk factors. Age and VLDL/LDL cholesterol impact women, while age and HDL cholesterol impact men.
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism
- Epidemiology
Background:
- Familial hypercholesterolemia (FH) is an inherited disorder causing high LDL cholesterol and increased coronary artery disease (CAD) risk.
- Genetic diversity in FH complicates understanding risk factor associations with CAD.
Purpose of the Study:
- To investigate the relationship between common risk factors and CAD in a homogeneous group of French Canadian FH patients.
- To identify sex-specific predictors of CAD in FH patients with a shared LDL receptor gene defect.
Main Methods:
- Studied 263 French Canadian FH patients (147 women, 116 men) with a common >10-kb LDL receptor gene deletion.
- Utilized multiple logistic regression to analyze associations between CAD and various risk factors including age, lipids, and lifestyle factors.
- Assessed predictors such as age, tendon xanthomas, smoking, hypertension, diabetes, ApoE, cholesterol, triglycerides, VLDL, LDL, HDL, and Lp(a).
Main Results:
- CAD was present in 35 women and 54 men, with earlier onset in men (38.8 years) vs. women (45.6 years).
- In FH women, significant CAD predictors included age (OR 1.10), VLDL cholesterol (OR 3.85), and LDL cholesterol (OR 1.42).
- In FH men, significant CAD predictors were age (OR 1.08) and HDL cholesterol (OR 0.14). Lipoprotein(a) was not significant.
Conclusions:
- CAD risk in FH is influenced by factors beyond just elevated LDL cholesterol.
- A distinct sex-specific effect of lipoproteins on CAD risk is evident in FH patients with this specific LDL receptor gene defect.
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 > 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 < .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 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.