title: Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes - findings from two community based cohorts of elderly.
abstract: BACKGROUND
  Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.
  
  
  METHODS
  The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).
  
  
  RESULTS
  In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatings TNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.
  
  
  CONCLUSIONS
  An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
authors.affiliation: Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: axelcefam@hotmail.com.
authors.forename: Axel C
authors.initials: AC
authors.lastname: Carlsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C Christofer
authors.initials: CC
authors.lastname: Juhlin
authors.affiliation: Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institutet, Stockholm, Sweden; Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Arnlöv
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000401:mortality; D018384:Oxidative Stress; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden; D016896:Treatment Outcome
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I
keywords: All-cause mortality; CRP; Community based cohort; Cytokines; Inflammation; Oxidative stress; Tumor necrosis factor