Preventive cardiologyUsefulness of Genetic Polymorphisms and Conventional Risk Factors to Predict Coronary Heart Disease in Patients With Familial Hypercholesterolemia
Section snippets
Methods
The study population was a cohort of heterozygous patients with FH recruited from 27 lipid clinics in The Netherlands from 1989 to 2002. More detailed information on the study design and study population was published previously.18 In brief, lipid clinics routinely send the DNA of patients with suspected FH to a central laboratory for low-density lipoprotein (LDL) receptor mutation analysis. We randomly selected a cohort of 4,000 persons from this DNA database, of whom 2,400 met the
Results
Table 2 lists the conventional characteristics and cumulative CHD risks at the age of 40, 50, and 60 years. During 66,904 person-years, 387 patients had ≥1 CHD event. Mean age of onset of the first CHD event was 49 ± 11 (SD) years. Eight genetic variants showed significant association with CHD risk (Table 3). Adjustment for hypertension, diabetes mellitus, BMI, plasma HDL and LDL cholesterol, and plasma triglycerides did not change results (data not shown).
Figure 1 shows the positive
Discussion
The present study showed that information on 14 currently known genetic variants associated with CHD risk yielded little discrimination for the prediction of CHD in patients with FH (c statistic 0.59). The c statistic of a prediction model already containing the conventional CHD risk factors increased from 0.75 to 0.76 when the 14 genetic variants were added to this prediction model. The clinical relevance of such a small increase in discriminative accuracy is questionable.
A number of
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