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Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis

Author:
  • Aisha Gohar
  • Isabel Gonçalves
  • Joyce Vrijenhoek
  • Saskia Haitjema
  • Ian van Koeverden
  • Jan Nilsson
  • Gert J. de Borst
  • Jean-Paul P. M. de Vries
  • Gerard Pasterkamp
  • Hester M den Ruijter
  • Harry Björkbacka
  • Saskia C A de Jager
Publishing year: 2017-03-22
Language: English
Pages: 430-436
Publication/Series: International Journal of Cardiology
Volume: 241
Document type: Journal article
Publisher: Elsevier

Abstract english

Background: Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases.We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated with carotid plaque characteristics. Methods: Circulating GDF-15 levels were determined by Luminex assay in a cohort of 1056 patients from the Athero-Express biobank. Composite endpoint was defined as major CVE, death and peripheral vascular interventions. Findings were validated in 473 patients from the independent Carotid Plaque Imaging Project biobank. Results: GDF-15 levels did not associate with secondary CVE in the total cohort. However, following a significant interaction with sex, it was found to be strongly, independently predictive of secondary CVE in women but not men (quartile 4 vs. quartile 1: HR 3.04 [95% CI 1.35-6.86], p = 0.007 in women vs. HR 0.96 [95% CI 0.66-1.40], p = 0.845 in men). This was also observed in the validation cohort (women: HR 2.28 [95% CI 1.04-5.05], p = 0.041), albeit dependent upon renal function. In addition, GDF-15 was associated with the presence of plaque smooth muscle cells and calcification. Conclusion: High circulating GDF-15 levels are predictive of secondary CVE in women but not in men with carotid atherosclerotic disease undergoing CEA, suggesting a potential use for GDF-15 as a biomarker for secondary prevention in women. Sex differences in the role of GDF-15 in atherosclerotic disease deserve further interest.

Keywords

  • Cardiac and Cardiovascular Systems
  • Atherosclerosis
  • Biomarker
  • GDF-15
  • Prognosis
  • Secondary outcome
  • Women

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • ISSN: 0167-5273
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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