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

Gohar, Aisha; Gonçalves, Isabel LU ; Vrijenhoek, Joyce; Haitjema, Saskia; van Koeverden, Ian; Nilsson, Jan LU ; de Borst, Gert J.; de Vries, Jean-Paul P. M.; Pasterkamp, Gerard and den Ruijter, Hester M, et al. (2017) In International Journal of Cardiology
Abstract

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... (More)

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.

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epub
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keywords
Atherosclerosis, Biomarker, GDF-15, Prognosis, Secondary outcome, Women
in
International Journal of Cardiology
publisher
Elsevier
external identifiers
  • scopus:85017404290
  • wos:000405455200074
ISSN
0167-5273
DOI
10.1016/j.ijcard.2017.03.101
language
English
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yes
id
50f0945c-a9c0-4f3b-aadb-285f063b8c1b
date added to LUP
2017-05-02 14:33:17
date last changed
2017-09-18 13:33:43
@article{50f0945c-a9c0-4f3b-aadb-285f063b8c1b,
  abstract     = {<p>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.</p>},
  author       = {Gohar, Aisha and Gonçalves, Isabel and Vrijenhoek, Joyce and Haitjema, Saskia and van Koeverden, Ian and Nilsson, Jan and de Borst, Gert J. and de Vries, Jean-Paul P. M. and Pasterkamp, Gerard and den Ruijter, Hester M and Björkbacka, Harry and de Jager, Saskia C A},
  issn         = {0167-5273},
  keyword      = {Atherosclerosis,Biomarker,GDF-15,Prognosis,Secondary outcome,Women},
  language     = {eng},
  month        = {03},
  publisher    = {Elsevier},
  series       = {International Journal of Cardiology},
  title        = {Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis},
  url          = {http://dx.doi.org/10.1016/j.ijcard.2017.03.101},
  year         = {2017},
}