Statin therapy induces gut leakage and neuromuscular disjunction in patients with chronic heart failure.

Statins are commonly used to limit the risk of cardiovascular diseases, including ischemic heart attack and stroke. However, treatment often leads to myopathy and muscle weakness. Therefore, a better understanding of underlying pathomechanism is needed to improve the clinical outcomes. Here we assessed the physical performance, including handgrip strength (HGS), gait speed (GS), and short physical performance battery (SPPB) in 172 patients diagnosed with chronic heart failure (CHF) treated with (n=50) or without (n=122) statin, and 59 controls. The plasma biomarkers, including sarcopenia marker C-terminal agrin fragment-22 (CAF22), intestinal barrier integrity marker zonulin, and C-reactive protein (CRP) were measured and correlated with the physical performance of patients. The HGS, SPPB scores and GS were significantly compromised in CHF patients vs. controls. Irrespective of etiology, significant elevation of plasma CAF22, zonulin, and CRP was observed in the CHF patients. There were strong inverse correlations of CAF22 with HGS (r2=0.34, P<0.0001), SPPB scores (r2=0.08, P=0.0001), and GS (r2=0.143, P<0.0001). Strikingly, CAF22 and zonulin were positively correlated with each other (r2=0.10, P=0.0002) and with the level of CRP in the CHF patients. Further investigations revealed a significant induction of CAF22, zonulin, and CRP in CHF patients taking statin vs. non-statin group. Consistently, HGS and GS were significantly lower, in the statin vs. non-statin CHF patients' group. Collectively, statin therapy adversely affects the neuromuscular junction and intestinal barrier, which potentially induces systemic inflammation and physical disability in patients with CHF. Further prospective confirmation of the findings is required in a well-controlled study.