Improving identification of familial hypercholesterolaemia in primary care: derivation and validation of the familial hypercholesterolaemia case ascertainment tool (FAMCAT).

OBJECTIVE: Heterozygous familial hypercholesterolaemia (FH) is a common autosomal dominant disorder. The vast majority of affected individuals remain undiagnosed, resulting in lost opportunities for preventing premature heart disease. Better use of routine primary care data offers an opportunity to enhance detection. We sought to develop a new predictive algorithm for improving identification of individuals in primary care who could be prioritised for further clinical assessment using established diagnostic criteria.
METHODS: Data were analysed for 2,975,281 patients with total or LDL-cholesterol measurement from 1 Jan 1999 to 31 August 2013 using the Clinical Practice Research Datalink (CPRD). Included in this cohort study were 5050 documented cases of FH. Stepwise logistic regression was used to derive optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy (area under receiver operating curve [AUC]).
RESULTS: The FH prediction model (FAMCAT), consisting of nine diagnostic variables, showed high discrimination (AUC 0.860, 95% CI 0.848-0.871) for distinguishing cases from non-cases. Sensitivity analysis demonstrated no significant drop in discrimination (AUC 0.858, 95% CI 0.845-0.869) after excluding secondary causes of hypercholesterolaemia. Removing family history variables reduced discrimination (AUC 0.820, 95% CI 0.807-0.834), while incorporating more comprehensive family history recording of myocardial infraction significantly improved discrimination (AUC 0.894, 95% CI 0.884-0.904).
CONCLUSION: This approach offers the opportunity to enhance detection of FH in primary care by identifying individuals with greatest probability of having the condition. Such cases can be prioritised for further clinical assessment, appropriate referral and treatment to prevent premature heart disease.