Different Pattern in Circulating MicroRNA‐22‐3p Levels Between Patients With Primary Versus Secondary Sarcopenia

Sarcopenia, characterized by decreased skeletal muscle mass and strength, is classified as "primary" (due to aging) or "secondary" (due to diseases). MicroRNA-22-3p (miR-22) regulates muscle differentiation and function. We assessed the diagnostic value of circulating miR-22 levels in patients with primary and secondary sarcopenia. miR-22 levels were evaluated in 61 older adults from the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) study and in 176 heart failure (HF) patients from the "Studies Investigating Co-morbidities Aggravating HF" (SICA-HF). miR-22 expression profile was measured in serum by miR-specific TaqMan quantitative real-time PCR. In SPRINTT, 33 participants (54.1%) had primary sarcopenia. Subjects with primary sarcopenia had slower gait speed (0.7 [0.6-0.8] vs. 0.8 [0.7-1.0] m/s; p < 0.001) than those without sarcopenia. Multivariate analysis showed miR-22 as an independent predictor of sarcopenia (adjusted OR 3.087, 95% CI 1.441-6.611, p = 0.004). In SICA-HF, 28 patients (15.9%) had secondary sarcopenia. Sarcopenic HF patients were older (74.5 [68.7-80.2] vs. 68.4 [60.9-74.8] years; p = 0.001), had lower left ventricular ejection fraction (31.1 [26.2-47.5] vs. 40.0 [30.0-55.0] %; p = 0.025), lower handgrip strength (31.1 ± 6.0 vs. 37.0 ± 13.0 kg; p = 0.016) and lower absolute peak oxygen uptake (1181.3 ± 379.5 vs. 1593.0 ± 487.0 mL/min; p < 0.001) compared with those without sarcopenia. Multivariate logistic regression analysis showed miR-22 as significantly associated with sarcopenia in HF patients (adjusted OR 0.409, 95% CI 0.193-0.867, p = 0.020). miR-22 levels are significantly associated with both primary and secondary sarcopenia, suggesting its potential as a novel epigenetic biomarker of skeletal muscle dysfunction.