title: Association between inflammatory biomarkers and all-cause, cardiovascular and cancer-related mortality.
abstract: BACKGROUND
  The inflammatory biomarker α1-acid glycoprotein (AGP) was found to have the strongest association with 5-year mortality in a recent study of 106 biomarkers. We examined whether AGP is a better biomarker of mortality risk than the more widely used inflammatory biomarkers interleukin-6 (IL-6) and C-reactive protein (CRP).
  
  
  METHODS
  We analyzed data for 6545 men and women aged 45-69 (mean 55.7) years from the Whitehall II cohort study. We assayed AGP, IL-6 and CRP levels from fasting serum samples collected in 1997-1999. Mortality followup was until June 2015. Cox regression analysis was used to model associations of inflammatory biomarkers with all-cause, cardiovascular and cancer-related mortality.
  
  
  RESULTS
  Over the mean follow-up of 16.7 years, 736 deaths occurred, of which 181 were from cardiovascular disease and 347 from cancer. In the model adjusted for all covariates (age, sex, socioeconomic status, body mass index, health behaviours and chronic disease), AGP did not predict mortality beyond the first 5 years of follow-up; over this period, IL-6 and CRP had stronger associations with mortality. When we considered all covariates and biomarkers simultaneously, AGP no longer predicted all-cause mortality over the entire follow-up period (adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.90-1.08). Only IL-6 predicted all-cause mortality (adjusted HR 1.22, 95% CI 1.12-1.33) and cancer-related mortality (adjusted HR 1.13, 95% CI 1.00-1.29) over the entire follow-up period, whereas CRP predicted only cardiovascular mortality (adjusted HR 1.30, 95% CI 1.06-1.61).
  
  
  CONCLUSIONS
  Our findings suggest that AGP is not a better marker of short-or long-term mortality risk than the more commonly used biomarkers IL-6 and CRP.
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK Archana.Singh-Manoux@inserm.fr.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shipley
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Bell
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Canonico
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK.
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.affiliation: INSERM U1018 Centre de recherche en Epidémiologie et Santé des Populations (Singh-Manoux, Canonico, Elbaz), Hôpital universitaire Paul-Brousse, Villejuif, France; Department of Epidemiology and Public Health (Shipley, Bell, Kivimäki), University College London, London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D009961:Orosomucoid / Q000032:analysis*; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D006113:United Kingdom
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D009961:Orosomucoid; D002097:C-Reactive Protein