Abstract 12015: Prediction Factors for Presence of a Mutation Causing Familial Hypercholesterolaemia
Introduction: Patients suffering from familial hypercholesterolaemia (FH) are at increased risk for atherosclerotic cardiovascular disease (CVD). Early detection of the disease is warranted since starting lipid-lowering therapy at young age has been shown to reduce the CVD risk. A definite diagnosis is provided by identification of the underlying molecular defect. To date, three clinical diagnostic criteria (MEDPED, Dutch Lipid Clinic Network and the Simon Broome Register) could be used to select patients that are eligible for molecular testing. However, the diagnostic accuracy of these criteria was shown to be low. The aim of our study is to identify predictors of the presence of an FH mutation in a large cohort of subjects screened for FH.
Methods: Data collected during the FH screening program in the Netherlands was used. Index patients were excluded from analysis, as were subjects in whom no lipid profile was measured. A multivariable logistic regression model was fitted using backward selection to identify risk factors associated with the presence of a FH mutation. Performance of the final model was assessed in terms of discrimination (c-statistic) and calibration (Hosmer-Lemeshow goodness-of-fit test).
Results: We examined 38,361 subjects, 13,894 of these had a molecular diagnosis of FH. Significant predictors of the presence of an FH mutation were found to be: increased LDL-cholesterol, low HDL-cholesterol, low triglycerides, premature CVD in medical history and a first degree relative with a LDL-cholesterol level on or above his or her 95th age and gender specific percentile (Table 1). The c-statistic was 0.850 (95% confidence interval: 0.845 - 0.854). The p-value for the Hosmer and Lemeshow test was ≤0.001.
Conclusion: We found patient characteristics that were strongly and independently associated with having a FH causing mutation. However, internal and external validation of this model is needed.
- © 2013 by American Heart Association, Inc.