Background: The renin-angiotensin system (RAS) activation is a proposed mechanism of muscle wasting (MW i.e., reduction in muscle mass). Although we reported that RAS inhibitors (RASIs) were associated with lower prevalence of MW in heart failure (HF) patients, the relationship between mineralocorticoid receptor (MR) signaling and MW has not been analyzed.Methods and Results: We analyzed data from 320 consecutive Japanese HF patients who underwent dual-energy X-ray absorptiometry scanning for assessment of appendicular skeletal muscle mass index (ASMI). In multiple linear regression analyses, plasma renin activity (PRA) was negatively correlated with ASMI in patients not receiving RASIs, indicating an untoward role of the RAS in MW. Results of analysis of covariance in which risk factors of MW served as covariates showed that use of MR antagonists (MRAs) was associated with lower ASMI and higher PRA in the non-RASIs group. The close relationship between use of MRAs and lower ASMI or higher PRA in the non-RASIs group was confirmed in analyses in which the differences in baseline characteristics between users and non-users of MRAs were minimized by using an inverse probability of treatment weighting.
Conclusions: Increased PRA by MR inhibition without concurrent RAS inhibition, possibly contributing to upregulation of angiotensin II signaling, may be associated with reduction in muscle mass.
Keywords: Heart failure; Mineralocorticoid receptor antagonists; Renin-angiotensin system; Sarcopenia; Skeletal muscle.