title: Use of multiple biomarkers to improve the prediction of death from cardiovascular causes.
abstract: BACKGROUND
  The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly.
  
  
  METHODS
  We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index).
  
  
  RESULTS
  During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit.
  
  
  CONCLUSIONS
  Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.
authors.affiliation: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Zethelius
authors.forename: Lars
authors.initials: L
authors.lastname: Berglund
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: Johan
authors.initials: J
authors.lastname: Arnlöv
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000097:blood; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D019210:Troponin I / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000097:blood
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein