Medicina de precisión: ncRNAs como herramienta diagnóstica para pacientes con intolerancia a estatinas de alto y muy alto riesgo cardiovascular

Abstract

Atherosclerotic cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Western populations and its association with dyslipidaemia is unquestionable. Statins are the treatment of first choice for their control, and are considered the cornerstone in the treatment of CVD. Statin-associated muscle symptoms (SMAE) are mostly a clinical self-diagnosis and the main reason for abandoning this treatment. We therefore consider it a priority need to identify biomarkers with discriminatory accuracy for a true diagnosis of statin intolerance (SI) in these patients. MicroRNAs (miRNAs) have emerged in recent years as molecules that offer valid biomarker roles involved in the regulation of multiple cellular events in cardiovascular diseases. In the present study, we evaluated plasma miRNAs as potential biomarkers to discriminate the SI population associated with muscle adverse effects from non-intolerant patients (NIE). This is a multicentre, prospective, case-control study. A total of 179 differentially expressed circulating miRNAs were examined in two cohorts of high and very high cardiovascular risk (CVR) patients: (i) NIE (n = 10); (ii) IE (n = 10). In the screening ten miRNAs were identified as overexpressed and validated in plasma from IE (n = 39) and NIE (n = 45). Five miRNAs (let-7c-5p, let-7d-5p, let-7f-5p, miR376a-3p and miR-376c-3p) were overexpressed in IE patient plasma. We propose a predictive marker of three miRNAs (let-7f-5p, miR-376a-3p and miR-376c3p) and clinical-biological variables, notably non-HDL cholesterol (c-non-HDL) and years of exposure to dyslipidaemia, to discriminate patients with IE. This model achieves sensitivity, specificity and area under the curve (AUC) of 83.67%, 88.57% and 89.10 respectively. In clinical practice, this miRNA set combined with clinical-biological variables can discriminate between subjects with SI vs. NIE. This multiparametric model may emerge as a potential diagnostic biomarker with clinical value in these intolerant patients and thus optimise the treatment of dyslipidaemias