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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 orcid ; 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 241. p.430-436
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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Biomarker, GDF-15, Prognosis, Secondary outcome, Women
in
International Journal of Cardiology
volume
241
pages
430 - 436
publisher
Elsevier
external identifiers
  • scopus:85017404290
  • pmid:28389123
  • wos:000405455200074
ISSN
0167-5273
DOI
10.1016/j.ijcard.2017.03.101
language
English
LU publication?
yes
id
50f0945c-a9c0-4f3b-aadb-285f063b8c1b
date added to LUP
2017-05-02 14:33:17
date last changed
2024-04-14 09:38:06
@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}},
  keywords     = {{Atherosclerosis; Biomarker; GDF-15; Prognosis; Secondary outcome; Women}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{430--436}},
  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}},
  doi          = {{10.1016/j.ijcard.2017.03.101}},
  volume       = {{241}},
  year         = {{2017}},
}