Combined Effect of Sarcopenia and Impaired Respiratory Function on All-Cause Death: A Nationwide Cohort Study.

BACKGROUND: Respiratory fitness and sarcopenia status have been reported to be cross-sectionally linked with each other and increase mortality risk. However, little is currently known regarding the connection between impaired respiratory function and sarcopenia and their joint effect on future death risk.

METHODS: This study included 12 027 participants (50.8% were women; mean [SD] age, 58.9 [9.3] years) from a nationwide, prospective cohort in China (China Health and Retirement Longitudinal Study). Respiratory function was assessed by peak expiratory flow (PEF). Sarcopenia status was assessed according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Time-to-event survival analyses and causal mediation analyses were conducted to assess the joint association of sarcopenia and reduced PEF with all-cause mortality.

RESULTS: During a mean follow-up of 8.64 years, 1536 deaths were recorded. After multivariable adjustment, the hazard ratios (HRs) for mortality were 1.51 (95% CI: 1.33-1.71) for possible sarcopenia and 1.67 (95% CI: 1.43-1.94) for diagnosed sarcopenia. A dose-dependent association between PEF and mortality was observed (p-nonlinearity > 0.05). The adjusted HRs per 1-SD decrease in PEF were 1.29 (95% CI: 1.18-1.41), 1.15 (95% CI: 1.03-1.29), and 1.49 (95% CI: 1.30-1.71) among individuals with nonsarcopenia, possible sarcopenia, and diagnosed sarcopenia, respectively (p interaction = 0.127). Causal mediation analysis demonstrated a bidirectional mediation effect, with both natural direct and indirect effects being statistically significant. Diagnosed sarcopenia was associated with excess mortality partly mediated by reduced PEF (total effect HR: 1.63, 95% CI: 1.38-1.92; natural indirect effect HR: 1.10, 95% CI: 1.07-1.14; proportion mediated: 18.5%). Conversely, sarcopenia mediated 10.0% and 7.0% of the reduced PEF-mortality pathway for possible and diagnosed sarcopenia, respectively. Compared with participants who had normal PEF and no sarcopenia, the adjusted HRs (95% CIs) for mortality were 1.52 (1.22-1.89) for possible sarcopenia with normal PEF, 1.73 (1.28-2.35) for diagnosed sarcopenia with normal PEF, 1.60 (1.36-1.88) for impaired PEF without sarcopenia, 2.22 (1.87-2.64) for impaired PEF with possible sarcopenia, and 2.44 (2.01-2.97) for impaired PEF with diagnosed sarcopenia. No significant risk heterogeneity was observed across sex, age or lifestyle subgroups.

CONCLUSIONS: Sarcopenia and impaired respiratory function are interrelated and jointly elevate mortality risk in middle-aged and older Chinese adults.