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Aims: To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography., Methods and Results: The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US 'Make Early Diagnosis to Prevent Early Death' (US-MEDPED), Simon Broome (SB) criteria, the 'familial hypercholesterolaemia case ascertainment tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harbouring 944 FH mutations.The study cohort consisted of 3267 patients [78.6% with coronary artery disease (CAD)]. FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve [area under the curves (AUCs)] in the range of 0.56-0.68. Using only low-density lipoprotein cholesterol (LDL-C) corrected for statin intake, an AUC of 0.68 was achieved., Conclusion: FH is up to four-fold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared with genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing., Lay Summary: In this study, we investigated the frequency of familial hypercholesterolaemia-a common genetic condition leading to markedly elevated low-density lipoprotein (LDL) cholesterol and increased risk of atherosclerosis-in 3267 patients undergoing coronary angiography according to commonly used diagnostic scoring systems and genetic testing., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background There are some inconsistencies on prevalence estimates of familial hypercholesterolemia (FH) in general population across Europe due to variable application of its diagnostic criteria. We aimed to investigate the FH epidemiology in Italy applying the Dutch Lipid Clinical Network (DLCN) score, and two alternative diagnostic algorithms to a primary care database. Methods We performed a retrospective population-based study using the Health Search IMS Health Longitudinal Patient Database (HSD) and including active (alive and currently registered with their general practitioners (GPs)) patients on December 31, 2014. Cases of FH were identified by applying DLCN score. Two further algorithms, based on either ICD9CM coding for FH or some clinical items adopted by the DLCN, were tested towards DLCN itself as gold standard. Results We estimated a prevalence of 0.01% for “definite” and 0.18% for “definite” plus “probable” cases as per the DLCN. Algorithms 1 and 2 reported a FH prevalence of 0.9 and 0.13%, respectively. Both algorithms resulted in consistent specificity (1: 99.10%; 2: 99.9%) towards DLCN, but Algorithm 2 considerably better identified true positive (sensitivity = 85.90%) than Algorithm 1 (sensitivity = 10.10%). Conclusion The application of DLCN or valid diagnostic alternatives in the Italian primary care setting provides estimates of FH prevalence consistent with those reported in other screening studies in Caucasian population. These diagnostic criteria should be therefore fostered among GPs. In the perspective of FH new therapeutic options, the epidemiological picture of FH is even more relevant to foresee the costs and to plan affordable reimbursement programs in Italy. [ABSTRACT FROM AUTHOR]