The mediation effects of metabolic and immune–inflammation factors on the depression–premature coronary heart disease association

Accumulated evidence confirmed depression was positively associated with coronary heart disease (CHD). But evidence of the association between depression and premature CHD is still unknown. To explore the association between depression and premature CHD, and to investigate whether and to what extent the association is mediated by metabolic factors and systemic immune–inflammation index (SII). In this large population–based cohort study based on the UK Biobank, 176,428 CHD–free (mean age: 52.70) adults were followed up for 15 years to detect incident premature CHD. Depression and premature CHD (mean age: female, 54.53; male, 48.13) were ascertained from self–report data and linked hospital–based clinical diagnosis. Metabolic factors included central obesity, hypertension, dyslipidemia, hypertriglyceridemia, hyperglycemia, and hyperuricemia. Systemic inflammation was evaluated by calculating SII, which equals platelet count (/L) × neutrophil count (/L) / lymphocyte count (/L). Data were analyzed using Cox proportional hazards models and generalized structural equation model (GSEM). During follow–up (median: 8.0 years, interquartile range: 4.0 to 14.0 years), 2990 participants developed premature CHD (1.7 %). The adjusted hazard ratio (HR) and 95 % confidence interval (CI) of premature CHD related to depression were 1.72 (1.44–2.05). The association between depression and premature CHD was 32.9 % mediated by comprehensive metabolic factors (β = 0.24, 95 % CI: 0.17–0.32) and 2.7 % by SII (β = 0.02, 95 % CI = 0.01–0.04), respectively. Concerning metabolic factors, the strongest indirect association was for central obesity, accounting for 11.0 % of the association between depression and premature CHD (β = 0.08, 95 % CI: 0.05–0.11). Depression was associated with an increased risk of premature CHD. Our study provided evidence that metabolic and inflammatory factors might play a mediating role in the association between depression and premature CHD, especially central obesity.