Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects

Abstract

Background. Growth-differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiac diseases. GDF-15 is commonly related to cardiovascular risk factors, inflammatory activity and cardiac abnormalities. However, it is not clear whether it might be an indicator of vascular pathologies as well. Methods. Circulating levels of GDF-15 were measured in 1004 elderly community dwellers participating in the PIVUS study. The relations of GDF-15 to biomarkers of endothelial activation (E-selectin, P-selectin, ICAM-1, VCAM-1), extracellular matrix degradation (MMP-9, TIMP-1), coagulatory activity (D-dimer, von Willebrand factor, prothrombin fragment 1 + 2, factor VIIa), and fibrinolytic activity (PAI-1 activity, tPA-antigen) were assessed by multiple linear regressions. Results. The median GDF-15 level was 1135 ng/L. By linear correlation analysis, GDF-15 exhibited a moderate relation to von Willebrand factor (r = 0.30), and weak, albeit significant relations (r = 0.13–0.29) to E-selectin, P-selectin, ICAM-1, VCAM-1, MMP-9, TIMP-1, D-dimer, PAI-1 activity and tPA-antigen. The relations to the assessed biomarkers of endothelial activation, TIMP-1, D-dimer and von Willebrand factor remained significant applying multiple linear regression models adjusted for clinical covariates and echocardiographic data. There were no significant relations between GDF-15 and biomarkers solely reflecting coagulatory activity. Conclusions. In the elderly, GDF-15 reflects endothelial activation and vascular inflammation and thus, multiple pathways involved in the development and progression of atherosclerosis.

Key Words::

• Growth-differentiation factor-15
• atherosclerosis
• endothelium
• vascular
• cell adhesion molecules
• blood coagulation factors
• tissue inhibitor of metalloproteinase-1

Acknowledgements

We are indebted to Nils Åsenblad for statistical support.

Funding sources: Grants from the German Ministry of Education and Research to Dr Wollert (BMBF, BioChancePlus) and the Swedish Heart-Lung Foundation to Dr Wallentin. The PIVUS-study had been supported by the Swedish Research Council, grant no. K2003-71X-00676-21A, and The Linné Foundation for Medical Research, Uppsala, Sweden.

Declaration of interest: Drs Wollert, Kempf, and Wallentin have filed a patent and have a contract with Roche Diagnostics to develop a GDF-15 assay for cardiovascular applications. The other authors have no conflicts to report.