Abstract
Introduction: Genetic testing for familial hypercholesterolaemia (FH) is not yet established for widespread use internationally to provide diagnostic confirmation, in part due to high cost and resource requirement. We need to establish whether genetic testing is clinically justified in terms of risk stratification and prediction of cardiovascular events.Methods:We performed a single tertiary cardiac centre retrospective evaluation of patients with FH managed within our genetic screening service. We evaluated the prevalence of cardiovascular events in genetically confirmed cases of FH compared to those unconfirmed upon genetic testing, to assess whether gene positivity confers a higher risk phenotype. We also compared the clinical characteristics of the genetically confirmed and unconfirmed group.Results:Amongst adult patients (≥18 years) with genetically confirmed heterozygous FH (n=87), 34% (30/87) had one or more documented CV events. In comparison a lower event rate was observed in adult patients with genetically unconfirmed FH (n=170) with 25% (42/170) experiencing one or more documented CV events. Additional cardiovascular risk factors were more prevalent in the unconfirmed group including hypertension, co-morbidities, higher age and body mass index which may have modified the difference in cardiovascular risk.Conclusion:Genetic testing in FH may be clinically justified and appears to identify a subset of patients with higher risk of cardiovascular events. However, the risk difference is modified by alternative cardiovascular risk factors and co-morbidities which may be more prevalent in genetically unconfirmed FH.
Highlights
Genetic testing for familial hypercholesterolaemia (FH) is not yet established for widespread use internationally to provide diagnostic confirmation, in part due to high cost and resource requirement
Amongst the 257 adult patients included in the study, 34% or 87/257 had genetically confirmed heterozygous FH; of which 94% had the LDLR mutation (82/87), 5% (4/87) had the ABOB mutation and only 1% (1/87) had the proprotein convertase subtilisin/kexin type 9 (PCSK9) mutation; consistent with the mutation distribution observed in earlier studies.[13,14]
In comparison a lower event rate was observed in adult patients with genetically unconfirmed FH (n=170) with 25% (42/170) experiencing one or more documented CV events
Summary
Genetic testing for familial hypercholesterolaemia (FH) is not yet established for widespread use internationally to provide diagnostic confirmation, in part due to high cost and resource requirement. We evaluated the prevalence of cardiovascular events in genetically confirmed cases of FH compared to those unconfirmed upon genetic testing, to assess whether gene positivity confers a higher risk phenotype. Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated LDL-cholesterol (LDL-C) which deposits in blood vessels, leading to premature cardiovascular disease It can deposit in tissues, causing external manifestations of the disease, namely tendinous xanthomas, xanthelasmas, and corneal arcus.[1] FH is not as rare as previously thought, affecting up to 250,000 individuals in the UK, with an estimated prevalence of 1/270 individuals in the general population with the heterozygous form.[2] In addition, it is currently estimated that only 15 to 20% of patients with FH are diagnosed.[3,4]. None of the patients within this paediatric cohort had cardiovascular events either at baseline or during the follow-up period.[5]
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