Background and aims: Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study. Methods: 836 hypercholesterolemic patients with LDL-C > 4.88 mmol/L were genotyped for FH causative gene variants in the LDLR, PCSK and APOB genes. Relatives of mutated patients were also analyzed by cascade screening. Results: Gene variant carriers were younger, presented higher LDL-C and DLCN score and lower HDL-C levels in comparison with hypercholesterolemic (HC) non-carriers and presented a five-fold higher prevalence of previous CV events. Carotid US data available in 490 subjects showed that variant carriers had an odds ratio of 3.66 (1.43-10.24) for atherosclerotic plaques in comparison with non-carriers. Scoring system were evaluated by ROC analysis in 203 subjects without missing DLCN items and with available pre-therapy LDL-C levels, and LDL-C levels (A.U.C. = 0.737) resulted to be more performing than the DLCN score (A.U.C. = 0.662), even including carotid US data (A.U.C. = 0.641) in a modified DLCN score version. Conclusions: the DLCN score failed to demonstrate a clear superiority in predicting FH gene variants in comparison with the measure of LDL-C levels in a retrospective case study.

Noto, D., Spina, R., Giammanco, A., Barbagallo, C.M., Ganci, A., Scrimali, C., et al. (2022). Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients. ATHEROSCLEROSIS, 347, 63-67 [10.1016/j.atherosclerosis.2022.03.012].

Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients

Noto, Davide
Primo
Writing – Original Draft Preparation
;
Spina, Rossella
Formal Analysis
;
Giammanco, Antonina
Investigation
;
Barbagallo, Carlo M
Membro del Collaboration Group
;
Ganci, Antonina
Membro del Collaboration Group
;
Scrimali, Chiara
Membro del Collaboration Group
;
Brucato, Federica
Membro del Collaboration Group
;
Misiano, Gabriella
Membro del Collaboration Group
;
Ciaccio, Marcello
Membro del Collaboration Group
;
Cefalù, Angelo Baldassare
Writing – Review & Editing
;
Averna, Maurizio
Ultimo
Conceptualization
2022-03-16

Abstract

Background and aims: Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study. Methods: 836 hypercholesterolemic patients with LDL-C > 4.88 mmol/L were genotyped for FH causative gene variants in the LDLR, PCSK and APOB genes. Relatives of mutated patients were also analyzed by cascade screening. Results: Gene variant carriers were younger, presented higher LDL-C and DLCN score and lower HDL-C levels in comparison with hypercholesterolemic (HC) non-carriers and presented a five-fold higher prevalence of previous CV events. Carotid US data available in 490 subjects showed that variant carriers had an odds ratio of 3.66 (1.43-10.24) for atherosclerotic plaques in comparison with non-carriers. Scoring system were evaluated by ROC analysis in 203 subjects without missing DLCN items and with available pre-therapy LDL-C levels, and LDL-C levels (A.U.C. = 0.737) resulted to be more performing than the DLCN score (A.U.C. = 0.662), even including carotid US data (A.U.C. = 0.641) in a modified DLCN score version. Conclusions: the DLCN score failed to demonstrate a clear superiority in predicting FH gene variants in comparison with the measure of LDL-C levels in a retrospective case study.
Settore MED/09 - Medicina Interna
Settore BIO/12 - Biochimica Clinica E Biologia Molecolare Clinica
Noto, D., Spina, R., Giammanco, A., Barbagallo, C.M., Ganci, A., Scrimali, C., et al. (2022). Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients. ATHEROSCLEROSIS, 347, 63-67 [10.1016/j.atherosclerosis.2022.03.012].
File in questo prodotto:
File Dimensione Formato  
Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients.pdf

non disponibili

Tipologia: Versione Editoriale
Dimensione 1.03 MB
Formato Adobe PDF
1.03 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/545659
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact