Skeletal Muscle Mass and Mortality in Heart Failure: Mediation Role of Systemic Immune-Inflammatory Index

Heart failure (HF)-related skeletal muscle wasting inversely affects the prognosis of HF, in which systemic inflammation may be involved. The relationships among skeletal muscle mass (SMM), systemic inflammation, and cardiovascular outcomes have not been clarified.

This study evaluated the associations of SMM with cardiovascular outcomes, systemic immune-inflammatory index (SII) with cardiovascular outcomes, and the mediation role of SII in the relationship between SMM and outcomes.

We included inpatients from the RED-CARPET trial (Real-world Data of Cardiometabolic ProtEcTion trial) with a definitive diagnosis of HF. We explored the associations of SMM with prognosis and SII with prognosis stratified by sex. Mediation analysis was applied for the role of SII in the association of SMM and the prognosis.

With a median follow-up of 4.9 years, 1402 patients with HF had 208 all-cause deaths and 106 cardiovascular deaths. Each 1-SD decrement in SMM was significantly associated with an increased risk of all-cause death (HR: 2.17; 95% CI: 1.20-3.91; P = 0.01 in males and HR: 2.90; 95% CI: 1.27-6.67; P = 0.012 in females). For cardiovascular death, the HR was 3.61 (95% CI: 1.56-8.40; P = 0.003) in males and 6.67 (95% CI: [2.33, 18.9]; P < 0.001) in females. Higher SII was associated with adverse outcomes. In the mediation analyses, SII was partially mediated in the relationship between SMM and cardiovascular death (7.1% [proportion-mediated 95% CI: 0.5%-26%]; P = 0.036 for males, and 5.4% [proportion mediated 95% CI: 0%-18.8%]; P = 0.064 for females).

Both low SMM and increased SII were significantly associated with unfavorable outcomes in HF. SII was partially mediated in the relationship between low SMM and cardiovascular death in HF.