New cardiovascular disease markers in patients with familial hypercholesterolemia carriers of genetic variants

Júnea Paolucci de Paiva Silvino; Cinthia Elim Jannes; Rodrigo Mendonça Cardoso Pestana; Lucas Paolucci de Paiva Silvino; Iêda de Fátima Oliveira Silva; Karina Braga Gomes

doi:10.1007/s40200-024-01537-w

New cardiovascular disease markers in patients with familial hypercholesterolemia carriers of genetic variants

J Diabetes Metab Disord. 2024 Dec 16;24(1):13. doi: 10.1007/s40200-024-01537-w. eCollection 2025 Jun.

Authors

Júnea Paolucci de Paiva Silvino¹, Cinthia Elim Jannes², Rodrigo Mendonça Cardoso Pestana¹, Lucas Paolucci de Paiva Silvino¹, Iêda de Fátima Oliveira Silva³, Karina Braga Gomes^{1

3}

Affiliations

¹ Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerias Brazil.
² Laboratório de Genética do Instituto do Coração (INCOR), Universidade de São Paulo, São Paulo, Brazil.
³ Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha. Belo Horizonte, Belo Horizonte, Minas Gerais 31270-901 Brazil.

PMID: 39697859
PMCID: PMC11649891 (available on 2025-12-16)
DOI: 10.1007/s40200-024-01537-w

Abstract

Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by elevated levels of low-density lipoprotein cholesterol (LDLc). The early diagnosis of FH can reduce unfavorable outcomes in this population, but genetic study is not available in all populations. This study aimed to evaluate new cardiovascular plasma markers (GDF-15, CXCL16, FABP3, FABP4, LIGHT, sCD14, ucMGP), as well as Lp(a) levels, in individuals genetically characterized for FH, classified according to treatment with statins.

Methods: Sequencing was performed by next generation sequencing (NGS) for 17 ICs and by the Sanger method for 120 relatives. Lp(a) was measured by turbidimetry and the other cardiovascular markers by the multiplex method for Luminex^®. Statistical analyses were performed using the R Platform version 4.2.2 program.

Results: 86 individuals carrying FH genetic variants and 51 non-carrier family members were identified. Lp(a) showed higher levels in the group with variants and was correlated to LDLc levels. FABP3 levels were higher in the group carrying variants using statins compared to the group without statins. The non-carrier group using statins showed higher levels of FABP4 compared to the carrier group using statins. The markers GDF-15, CXCL16, LGHT, sCD14 and ucMGP did not show a significant difference between groups, but GDF-15 and sCD14 were correlated to LDLc levels.

Conclusions: Lp(a) and the new markers FABP3 e FABP4 are associated with FH, their levels are modulated by the use of statins, and they could be potential markers to assess the disease when genetic testing is not available.

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01537-w.

Keywords: Cardiovascular markers; Familial hypercholesterolemia; Genetic variants; Lipid profile; Lp(a).

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