Association between serum cotinine and muscle mass: The mediating role of systemic inflammation in NHANES 2013–2018

INTRODUCTIONSmoking is a modifiable risk factor for muscle loss, but the underlying mechanisms are not fully understood.This study investigated the association between serum cotinine and appendicular skeletal muscle mass index (ASMI) and the mediating role of the systemic inflammation response index (SIRI).METHODS Data from NHANES 2013-2018 were used for secondary analysis.A total of 4174 adults with complete records of cotinine and data for calculating ASMI and SIRI were included.Weighted multiple linear regression assessed associations of cotinine with ASMI and SIRI, and univariate analysis was performed to screen relevant variables.Mediation analysis with SIRI as the mediator subsequently quantified the indirect effect.All analyses were performed after adjustment for potential confounders.RESULTS In females, ASMI was significantly lower in the high-cotinine group than in the low-cotinine group; no significant difference was observed between the two groups in males.Univariate analysis demonstrated significant negative correlations of cotinine and SIRI with ASMI.Across all weighted regression models, cotinine was negatively associated with ASMI (fully adjusted, β= -0.000; 95% CI: -0.000 --0.000) and positively associated with SIRI (fully adjusted, β=0.001; 95% CI: 0.001-0.001).In the fully adjusted model, SIRI was negatively associated with ASMI (β= -0.003; 95% CI: -0.005 --0.001).Mediation analysis showed that SIRI partially mediated the cotinine-ASMI relationship, with a proportion mediated of 14.170%.CONCLUSIONS Elevated cotinine levels are significantly associated with decreased muscle mass, and this association is partially mediated by systemic inflammation.