Abstract Background Depression and sarcopenia are increasingly recognized as interrelated conditions with significant health implications. Purpose This study investigates the independent and combined effects of sarcopenia and depression on incident cardiovascular disease (CVD) and all-cause mortality in Chinese adults, with an emphasis on their potential interaction and mediating effects. Methods Data were drawn from a national cohort of 9,799 middle-aged and older adults without prior CVD. Participants were sampled from 150 counties/districts and 450 communities across 28 provinces in China. Sarcopenia was defined according to the AWGS 2019 criteria, incorporating measures of muscle mass, strength, and physical performance. Depression was assessed with the validated 10-item Center for Epidemiologic Studies Depression Scale. Time-to-event survival analysis, interaction analysis, and causal mediation analysis were performed to evaluate the associations of sarcopenia, depression, and their interplay with CVD (heart disease and stroke) and mortality. Results Over a mean follow-up of 7.7 years, 1,846 CVD cases and 1,166 deaths occurred. Depression showed a dose-dependent association with increased CVD risk but was inversely associated with all-cause mortality. After adjusting for confounders, sarcopenia was linked to higher risks of CVD (16% increase), heart disease (22% increase), and mortality (56% increase), whereas no significant associations were observed with stroke. Depression independently increased risks of total CVD (19%), heart disease (20%), and stroke (30%), but was not significantly associated with mortality. The concurrent presence of sarcopenia and depression led to the highest risk of adverse outcomes: hazard ratios for CVD, heart disease, stroke, and mortality were 1.33 (95% CI: 1.16–1.53), 1.39 (95% CI: 1.19–1.63), 1.28 (95% CI: 1.01–1.62), and 1.67 (95% CI: 1.39–2.00), respectively. Interaction tests were not statistically significant. Mediation analysis revealed that depression partially mediated the sarcopenia–CVD association (12.7%, P=0.004), particularly for low physical performance (21.8%, P=0.006). Conversely, sarcopenia significantly mediated the depression–mortality association (33.8%, P0.0001), but depression did not mediate the sarcopenia–mortality link (1.2%, P=0.1777). Conclusions Depression and sarcopenia independently and jointly elevated the risk of CVD and all-cause mortality among Chinese adults. Depression partially mediated the sarcopenia–CVD association, especially for low physical performance. However, while sarcopenia mediated the depression–mortality association, depression did not mediate the sarcopenia–mortality relationship.Figure 1
Lan et al. (Sat,) studied this question.