A microRNA Signature for the Diagnosis of Statins Intolerance
dc.contributor.author
dc.date.accessioned
2022-09-21T12:20:54Z
dc.date.available
2022-09-21T12:20:54Z
dc.date.issued
2022-07-24
dc.identifier.issn
1661-6596
dc.identifier.uri
dc.description.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
dc.description.sponsorship
: This work was supported by grants in the framework of the European Regional Development Fund (ERDF) Integrated Territorial Initiative (ITI PI0048-2017 and ITI PI0017-2019), a research
grant from the Spanish Society of Cardiology for Basic Research in Cardiology (PI0012-2019), Plan
Propio de INIBICA (PI-INBICA 2019-13), Foundation Progreso y Salud PEER (2020-019)
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
MDPI (Multidisciplinary Digital Publishing Institute)
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.3390/ijms23158146
dc.relation.ispartof
International Journal of Molecular Sciences, 2022, vol. 23, núm. 15, p. 8146
dc.relation.ispartofseries
Articles publicats (IdIBGi)
dc.rights
Attribution 4.0 International
dc.rights.uri
dc.subject
dc.title
A microRNA Signature for the Diagnosis of Statins Intolerance
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
035535
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1422-0067