Clinical and genetic diagnosis of familial hypercholesterolaemia in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health Study.

Autor:	Molnar S; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany., Scharnagl H; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria., Delgado GE; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany., Krämer BK; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany., Laufs U; Department of Cardiology, University Hospital Leipzig, Leipzig, Germany., März W; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.; Synlab Academy, Mannheim, Germany., Kleber ME; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.; Synlab MVZ Humangenetik Mannheim, Mannheim, Germany., Katzmann JL; Department of Cardiology, University Hospital Leipzig, Leipzig, Germany.
Jazyk:	angličtina
Zdroj:	European heart journal. Quality of care & clinical outcomes [Eur Heart J Qual Care Clin Outcomes] 2024 Nov 05; Vol. 10 (7), pp. 632-640.
DOI:	10.1093/ehjqcco/qcad075
Abstrakt:	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.)
Databáze:	MEDLINE
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