The mediation role of metabolic syndromes on the association between depression and cardiovascular diseases in the UK Biobank population study

This study aimed to assess the potential mediating role of metabolic syndrome (MetS) between depression and cardiovascular disease (CVD). 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. 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 12.2% 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%). MetS partially mediates the association between depression and CVD during midlife. Unhealthy waist circumference may be the most important potential target for preventive interventions. • Depression is significantly associated with an increased risk of cardiovascular disease (31% higher risk). • Metabolic syndrome mediates 12.9% of the association between depression and CVD. • Waist circumference is the strongest mediating factor within MetS, accounting for 10.2%. • MetS has a stronger mediating role in males than females; blood pressure only mediates in those ≥55 years.