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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of morbidity and mortality in Western societies. Statins are the first-choice therapy for dislipidemias and are considered the cornerstone of ASCVD. Statin-associated muscle symptoms are the main reason for dropout of this treatment. There is an urgent need to identify new biomarkers with discriminative precision for diagnosing intolerance to statins (SI) in patients. MicroRNAs (miRNAs) have emerged as evolutionarily conserved molecules that serve as reliable biomarkers and regulators of multiple cellular events in cardiovascular diseases. In the current study, we evaluated plasma miRNAs as potential biomarkers to discriminate between the SI vs. non-statin intolerant (NSI) population. It is a multicenter, prospective, case-control study. A total of 179 differentially expressed circulating miRNAs were screened in two cardiovascular risk patient cohorts (high and very high risk): (i) NSI (n = 10); (ii) SI (n = 10). Ten miRNAs were identified as being overexpressed in plasma and validated in the plasma of NSI (n = 45) and SI (n = 39). Let-7c-5p, let-7d-5p, let-7f-5p, miR-376a-3p and miR-376c-3p were overexpressed in the plasma of SI patients. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. We propose a three-miRNA predictive fingerprint (let-7f, miR-376a-3p and miR-376c-3p) and several clinical variables (non-HDLc and years of dyslipidemia) for SI discrimination; this model achieves sensitivity, specificity and area under the receiver operating characteristic curve (AUC) of 83.67%, 88.57 and 89.10, respectively. In clinical practice, this set of miRNAs combined with clinical variables may discriminate between SI vs. NSI subjects. This multiparametric model may arise as a potential diagnostic biomarker with clinical value.

Details

Title
A microRNA Signature for the Diagnosis of Statins Intolerance
Author
Mangas, Alipio 1 ; Pérez-Serra, Alexandra 2   VIAFID ORCID Logo  ; Bonet, Fernando 3   VIAFID ORCID Logo  ; Muñiz, Ovidio 4 ; Fuentes, Francisco 5 ; Gonzalez-Estrada, Aurora 4 ; Campuzano, Oscar 6 ; Rodriguez Roca, Juan Sebastian 7 ; Alonso-Villa, Elena 3 ; Toro, Rocio 3 

 Research Unit, Biomedical Research and Innovation Institute of Cadiz (INiBICA), Puerta del Mar University Hospital, 11009 Cádiz, Spain; [email protected] (A.M.); [email protected] (E.A.-V.); Medicine Department, School of Medicine, University of Cadiz, 11002 Cádiz, Spain; Lipid and Atherosclerotic Unit, Internal Medicine Department, Puerta del Mar University Hospital, 11009 Cadiz, Spain; [email protected] 
 Cardiology Service, Hospital Josep Trueta, University of Girona, 17007 Girona, Spain; [email protected] (A.P.-S.); [email protected] (O.C.); Cardiovascular Genetics Center, University of Girona-IDIBGI, 17007 Girona, Spain 
 Research Unit, Biomedical Research and Innovation Institute of Cadiz (INiBICA), Puerta del Mar University Hospital, 11009 Cádiz, Spain; [email protected] (A.M.); [email protected] (E.A.-V.); Medicine Department, School of Medicine, University of Cadiz, 11002 Cádiz, Spain 
 UCERV, UCAMI, Servicio de Medicina Interna, Hospital Virgen del Rocío, 41013 Seville, Spain; [email protected] (O.M.); [email protected] (A.G.-E.) 
 Lipid and Atherosclerosis Unit, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Córdoba, 14004 Córdoba, Spain; [email protected]; Centro de Investigación Biomédica en Red, Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain 
 Cardiology Service, Hospital Josep Trueta, University of Girona, 17007 Girona, Spain; [email protected] (A.P.-S.); [email protected] (O.C.); Cardiovascular Genetics Center, University of Girona-IDIBGI, 17007 Girona, Spain; Centro de Investigación Biomédica en Red, Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain; Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain 
 Lipid and Atherosclerotic Unit, Internal Medicine Department, Puerta del Mar University Hospital, 11009 Cadiz, Spain; [email protected] 
First page
8146
Publication year
2022
Publication date
2022
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2700753099
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.