title: The Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers.
abstract: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality.
  
  
  
  Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects.
  
  
  
  During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality.
  
  
  
  Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.
authors.affiliation: From the UK Clinical Research Collaboration Centre of Excellence for Public Health (Hughes, Patterson, Woodside, Donnelly, Linden, Esquirol, Kee), Queens University of Belfast, Northern Ireland, United Kingdom; Clinic for General and Interventional Cardiology (Hughes, Blankenberg, Zeller), University Heart Centre Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK) Partner Site Hamburg/Lübeck/Kiel (Hughes, Blankenberg, Zeller), Germany; MRC Epidemiology Unit (Hughes), University of Cambridge, Cambridge, England, United Kingdom; Department of Psychology (Appleton), Bournemouth University, Dorset, United Kingdom; and UMR 1027 Université Paul Sabatier-CHU (Esquirol), Toulouse, France.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Hughes
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Patterson
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Appleton
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Jayne V
authors.initials: JV
authors.lastname: Woodside
authors.forename: Michael
authors.initials: M
authors.lastname: Donnelly
authors.forename: Gerard
authors.initials: G
authors.lastname: Linden
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Yolande
authors.initials: Y
authors.lastname: Esquirol
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D002423:Cause of Death; D003863:Depression / Q000453:epidemiology / Q000503:physiopathology*; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology; D011379:Prognosis
chemical_list: D015415:Biomarkers