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To Correct or not to Correct (for treatment): Estimating Pre-treatment LDL-C Concentrations in Genetically Characterized Patients with Familial Hypercholesterolaemia on Lipid-lowering Medication

2024-05Conference object Restricted access
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dc.contributor.authorStevens, C.A.T.
dc.contributor.authorElshorbagy, A.
dc.contributor.authorVallejo-Vaz, A.J.
dc.contributor.authorDharmayat, K.
dc.contributor.authorLyons, A.
dc.contributor.authorBourbon, M.
dc.contributor.authorChora, J.
dc.contributor.authorHumphries, S.E.
dc.contributor.authorCatapano, A.L.
dc.contributor.authorHovingh, G.
dc.contributor.authorMata, P.
dc.contributor.authorSantos, R.
dc.contributor.authorSoran, H.
dc.contributor.authorWatts, G.F.
dc.contributor.authorRaal, F.
dc.contributor.authorFreiberger, T.
dc.contributor.authorRay, K.K.
dc.contributor.authoron behalf of all the EAS FHSC Collaborators
dc.date.accessioned2024-07-10T12:46:22Z
dc.date.available2024-07-10T12:46:22Z
dc.date.issued2024-05
dc.description.abstractBackground and Aims: Pretreatment LDL-C measurements aid familial hypercholesterolaemia (FH) diagnosis, and are crucial in epidemiologic studies investigating FH, but are often unavailable because individuals are already on lipid-lowering medication (LLM). Several formulae have been reported to estimate pre-treatment LDL-C in people on LLM by ‘correcting’ their LDL-C concentrations for LLM type and dosage, based on observational or trial evidence of drug efficacy. We compared 4 published correction factors in estimating pre-treatment LDL-C in patients with FH. Methods: Cross-sectional analysis of adults with pathogenic/likely-pathogenic FH variants in the EAS-FH Studies Collaboration (FHSC) Registry. At the time of LDL-C measurement, N=3012 participants were not on LLM (Untreated group), and N=3226 were on LLM monotherapy, with information on LLM type and dosage allowing estimation of pre-treatment LDL-C (Corrected group) based on correction factors by Ruel 2018, Ellis 2016, Haralambos 2015 and Besseling 2014. We compared the groups for clinical characteristics and LDL-C by gene and variant. Results: The Corrected group was older than the Untreated group (median[IQR]: 50[39,63] vs. 38[28,50]y), with similar proportion of women (54.5% vs. 56.8%;p=0.14) but more comorbidities (all p<0.001). In the Corrected group, 3120 were on statins, 106 on ezetimibe, none on PCSK9-inhibitors. The Corrected group had higher LDL-C vs. Untreated group, with the difference greater at upper percentiles, regardless of correction factor. LDL-C was highest in those with LDLR>APOB>PCSK9 gene variants, but Corrected was still higher than Untreated LDL-C within each gene group. The difference in Corrected vs. Untreated LDL-C varied by variant, from +0.6 to +3.5mmol/L (20 commonest variants). The LDL-C differences persisted after adjusting for age, sex and comorbidities. Conclusions: Application of current LDL-C correction factors appears to overestimate pre-treatment LDL-C in epidemiologic settings, or the Untreated and Corrected groups might have inherently different LDL-C profiles. The accuracy of using LDL-C correction factors in FH therefore warrants further investigation.pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/9197
dc.language.isoengpt_PT
dc.peerreviewednopt_PT
dc.subjectFamilial Hypercholesterolaemiapt_PT
dc.subjectLipid-lowering Medicationpt_PT
dc.subjectCorrection Factorspt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titleTo Correct or not to Correct (for treatment): Estimating Pre-treatment LDL-C Concentrations in Genetically Characterized Patients with Familial Hypercholesterolaemia on Lipid-lowering Medicationpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceLyon, Françapt_PT
oaire.citation.titleEAS 92nd Congress, European Atherosclerosis Society, 26-29 maio 2024pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT

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