PLASMA NUCLEIC ACIDS AS POTENTIAL PREDICTORS OF STATIN ASSOCIATED MUSCLE SYMPTOMS

Introduction Statin-associated muscle symptoms (SAMS) are the most common undesirable side effect (USE) of widely indicated statin therapy. So far, appropriate biochemical markers allowing early prediction and confirmation of the causal association between SAMS and statin use are missing. Plasma cell-free nucleic acids (miRNAs, nucleic and mitochondrial DNAs) could be promising new markers of muscle damage.
Methods Using quantitative PCR, we analyzed plasma concentrations of three muscle-specific miRNAs (133a-3p, 1-3p, and 23a-5), nucleic DNA (markers at IL-6 and FTO genes) and mitochondrial DNA (two independent markers) in a total of seventeen adult subjects (13 men and 4 women) with acute coronary events who were treated with statins after (but not before) the event. One sample was available before statin treatment and three samples during the first year of statin treatment. Because of the variance in cell-free nucleic acid concentrations, values were compared to the untreated sample (arbitrary standardised values of 1.00 for each subject/marker analyzed).
Results Seven of seventeen (i.e. 41%) subjects reported different degrees of SAMS on treatment. The relative change of unadjusted concentrations (significant at P < 0.05 in two cases) of all three miRNAs analyzed was (when compared with the first examination) different in subjects with SAMS (e.g., miRNA 1-3p; 1.00 → 1.06 ± 0.28 → 1.07 ± 0.25 → 1.10 ± 0.40) compared with subjects without (1.00 → 1.43 ± 0.52 → 1.54 ± 0.74 → 1.52 ± 0.69). Changes of cell free DNAs in time were independent on SAMS presence.
Conclusion Concentrations of regulatory miRNAs (but probably not cfDNA) may be markers of muscle damage induced by statin treatment.

Supported by Ministry of Health of the Czech Republic, grant nr. NU21-01-00146. All rights reserved.