title: Blood-borne biomarkers of mortality risk: systematic review of cohort studies.
abstract: BACKGROUND
  Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.
  
  
  OBJECTIVE
  To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.
  
  
  METHODS
  Four databases (Medline, Embase, Scopus, Web of Science) were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.
  
  
  RESULTS
  From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033), N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001) and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001). There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of metalloproteinases 1 and tumour necrosis factor receptor II may predict mortality risk. There was equivocal evidence for the utility of 14 biomarkers and no association with mortality risk for CD40 ligand, cortisol, dehydroepiandrosterone, ferritin, haemoglobin, interleukin-12, monocyte chemoattractant protein 1, matrix metalloproteinase 9, myelopereoxidase, P-selectin, receptor activator of nuclear factor KappaB ligand, sex hormone binding globulin, testosterone, transferrin, and thyroid stimulating hormone and thyroxine.
  
  
  CONCLUSIONS
  Twenty biomarkers should be prioritised as potential predictors of mortality in future studies. More studies using standardised protocols and reporting methods, and which focus on mortality rather than risk of disease or health status as an outcome, are needed.
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Biomedical Research Building, Campus for Ageing & Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Barron
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Biomedical Research Building, Campus for Ageing & Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors.forename: Jose
authors.initials: J
authors.lastname: Lara
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Biomedical Research Building, Campus for Ageing & Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom; Institute of Health and Society, Newcastle University, Baddiley-Clark Building, Faculty of Medical Sciences, Newcastle upon Tyne, NE2 4AX, United Kingdom; Fuse, UKCRC Centre for Translational Research in Public Health, Institute of Health & Society, Baddiley-Clark Building, Faculty of Medical Sciences, Newcastle upon Tyne, NE2 4AX, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: White
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Biomedical Research Building, Campus for Ageing & Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008136:Longevity; D016239:MEDLINE; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000401:mortality*
chemical_list: D015415:Biomarkers