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European Heart Journal Advance Access originally published online on June 26, 2009
European Heart Journal 2009 30(19):2346-2353; doi:10.1093/eurheartj/ehp261
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study

Lars Lind1, Lars Wallentin1, Tibor Kempf2, Heike Tapken2, Anja Quint2, Bertil Lindahl1, Sylvia Olofsson1, Per Venge1, Anders Larsson1, Johannes Hulthe1, Anders Elmgren1 and Kai C. Wollert2,*

1 Department of Medicine (Cardiology and Clinical Chemistry) and Uppsala Clinical Research Centre, University of Uppsala, 75185 Uppsala, Sweden
2 Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Received 19 January 2009; revised 20 April 2009; accepted 5 June 2009; online publish-ahead-of-print 26 June 2009.

* Corresponding author. Tel: +49 511 532 4055, Fax: +49 511 532 5307, Email: wollert.kai{at}mh-hannover.de

Aims: Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies.

Methods and results: To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure.

Conclusion: GDF-15 carries information on CV dysfunction and disease that is not captured by traditional CV risk factors in elderly individuals.

Key Words: GDF-15 • Biomarker • Endothelial function • Atherosclerosis • Hypertrophy • Heart failure


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