Abstract
OBJECTIVE: This study aimed to assess the potential mediating role of metabolic syndrome (MetS) between depression and cardiovascular disease (CVD). METHODS: This population-based prospective cohort study analyzed data collected between March 2006 and December 2010 from 353,610 participants aged 37 to 73 years from the UK Biobank. Depression was assessed using self-reported questionnaires and linked hospital-based clinical depression diagnosis. MetS was defined as the presence of 3 or more of unhealthy waist circumference, dyslipidemia, hypertension, hyperglycemia and hypertriglyceridemia. Incident CVD was identified through linked hospital and death records. Counterfactual-based mediation analysis was conducted to estimate the mediating effect. RESULTS: After an average follow-up of 15 years, 38424 CVD events occurred in 353,610 participants (55% women; mean age at baseline, 56 years). Study findings indicated a significant direct association between depression and CVD (HR = 1.310; 95% CI, 1.277-1.342). A significant indirect association was also observed between depression and CVD (HR = 1.035; 95% CI, 1.031-1.037), indicating that 12.9% of the association of depression with CVD was mediated by MetS. Among the components of MetS, unhealthy waist circumference showed the largest estimated mediated proportion (PM = 10.2%; NIE HR = 1.027). MetS accounted for a higher proportion of the association between depression and CVD in males (PM = 14.2%; NIE HR = 1.026), than females (PM = 11.2%; NIE HR = 1.034). Blood pressure mediated the association only in participants aged ≥55 years (PM = -2.2%). CONCLUSION: MetS partially mediates the association between depression and CVD during midlife. Unhealthy waist circumference may be the most important potential target for preventive interventions.