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Original article
Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes
  1. M Resl1,2,
  2. M Clodi2,
  3. G Vila1,
  4. A Luger1,
  5. S Neuhold3,
  6. R Wurm4,
  7. C Adlbrecht4,
  8. G Strunk5,6,
  9. M Fritzer-Szekeres7,
  10. R Prager8,
  11. R Pacher4,
  12. M Hülsmann4
  1. 1Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
  2. 2Department of Medicine, St. John of God's Hospital Linz, Institute for Cardiometabolic Research JKU, Linz, Austria
  3. 3Department of Medicine IV, Kaiser Franz Joseph Spital, Vienna, Austria
  4. 4Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
  5. 5Technical University Dortmund, Germany
  6. 6FH Campus Vienna and Complexity Research, Vienna, Austria
  7. 7Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
  8. 8Karl Landsteiner Institute for Nephrology and Diabetes, Hietzing Hospital Vienna, Vienna, Austria
  1. Correspondence to Professor M Huelsmann, Division of Cardiology, Department of Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria; martin.huelsmann{at}


Objective 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.

Methods 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.

Results 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%).

Conclusions GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes.

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  • RPa and MH contributed equally to this paper.

  • Contributors MR: researched data, performed statistical analysis and wrote the manuscript. MC: designed the study researched data and revised the manuscript. GV: researched data and participated in writing the manuscript. AL: designed and conducted the study and revised the manuscript. SN, RW, CA, MF-S and RPr: revised the manuscript and researched data. GS: performed statistical analysis and participated in writing the manuscript. RPa: revised the manuscript and researched data and did data quality assessment; MH: designed the study and participated in writing the manuscript.

  • Competing interests None declared.

  • Ethics approval Ethics committee of the Medical University of Vienna.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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