title: Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes.
abstract: We hypothesised that biomarkers representing different pathophysiological pathways of atherosclerosis namely growth differentiation factor 15 (GDF-15), N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) could enhance cardiovascular risk prediction in patients with type 2 diabetes mellitus.
  
  
  
  This is a prospective study in 746 patients with type 2 diabetes mellitus, who were followed up for 60 months. The primary endpoint was defined as unplanned hospitalisation for cardiovascular disease or death. The prognostic performance of the biomarkers of interest (GDF-15 in comparison with NT-proBNP and hs-TnT) was evaluated in univariate as well as in stepwise Cox regression models. HRs are presented per standard unit increase.
  
  
  
  The primary endpoint was registered in 171 patients (22.9%). In univariate Cox regression models, GDF-15 as well as hs-TnT provided significant prognostic information. Even after adjusting for established cardiovascular risk factors, GDF-15, hs-TnT and NT-proBNP remained strong independent predictors of the endpoint (logGDF-15: HR 1.37, p<0.01, CI 1.12 to 1.68; loghs-TnT: HR 1.43, p<0.01, CI 1.13 to 1.1.82; logNT-proBNP: HR 1.45, p<0.01, CI 1.26 to 1.66). The number of elevated markers showed a strong complementarity to predict future long-term risk. Adding hs-TnT and GDF-15 to a zero model already including NT-proBNP led to a net reclassification improvement (NRI) of 33.6% (CI 16.0% to 50.8%, NRI for patients with event: 11.1% CI -4.7% to 26.6%, for patients without event: 22.5% CI 13.6% to 30.5%).
  
  
  
  GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes.
authors.affiliation: Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.|Department of Medicine, St. John of God's Hospital Linz, Institute for Cardiometabolic Research JKU, Linz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Resl
authors.affiliation: Department of Medicine, St. John of God's Hospital Linz, Institute for Cardiometabolic Research JKU, Linz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Clodi
authors.affiliation: Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Vila
authors.affiliation: Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Luger
authors.affiliation: Department of Medicine IV, Kaiser Franz Joseph Spital, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Neuhold
authors.affiliation: Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.identifier: 0000-0003-3027-7775
authors.initials: R
authors.lastname: Wurm
authors.affiliation: Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Adlbrecht
authors.affiliation: Technical University Dortmund, Germany.|FH Campus Vienna and Complexity Research, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Strunk
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.affiliation: Karl Landsteiner Institute for Nephrology and Diabetes, Hietzing Hospital Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Prager
authors.affiliation: Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Pacher
authors.affiliation: Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hülsmann
mesh_terms: D000328:Adult; D000368:Aged; D001317:Austria; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D018450:Disease Progression; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D020107:Troponin T / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain