The effects of physical activity and sedentary behavior in the associations between cardiovascular diseases and depression: A four-way decomposition

•Based on the four-way decomposition, we observed a strong reference interaction of moderate recreational activity in the associations between CVDs and depression, explaining the 94.08% of total effects.•The effects of cardiovascular diseases on depression were also mediated by moderate recreational activity, especially in females.•For sedentary behavior, only pure indirect effect was found to affect the associations between cardiovascular diseases and depression, especially in females. Negative effects of cardiovascular diseases (CVDs) on depression have been reported, but the relative contribution of physical activity (PA) and sedentary behavior (SB) to such effects remains unclear. Our objective was to precisely quantify the effects modified or mediated by PA and SB using the recently developed four-way effect decomposition. Our analysis included 22,117 adults (aged≥20 years) participating in the 2007–2016 National Health and Nutrition Examination Survey (NHANES). Depression was assessed by the Patient Health Questionnaire-9. Moderate recreational activity (MRA), moderate work activity (MWA), and walk or bicycle for transportation, were measured by the Global Physical Activity Questionnaire (GPAQ). A four-way decomposition was applied with PA and SB as mediator to decompose the total effects of CVDs on depression into four components: controlled direct effect (CDE), pure indirect effect (PIE), reference interaction (INTref), and mediated interaction effect (INTmed). There were statistically significant associations between CVDs, MRA, and depression, with the adjusted odds ratios (95% confidence intervals) of being 1.73 (1.42~2.30), 1.81 (1.42~2.30), respectively. With MRA as a mediator, there were interaction and mediation effects in the associations between CVDs and depression, and the proportions attributable of INTref, INTmed, and PIE were 94.08% (P