Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis
Gohar, Aisha; Gonçalves, Isabel; Vrijenhoek, Joyce; Haitjema, Saskia; van Koeverden, Ian; Nilsson, Jan; de Borst, Gert J.; de Vries, Jean Paul; Pasterkamp, Gerard; den Ruijter, Hester M.; Björkbacka, Harry; de Jager, Saskia C.A.
(2017) International Journal of Cardiology, volume 241, pp. 430 - 436
(Article)
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
... read more
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.
show less
Download/Full Text
Keywords: Atherosclerosis, Biomarker, GDF-15, Prognosis, Secondary outcome, Women, General Medicine, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 0167-5273
Publisher: Elsevier Ireland Ltd
Note: Funding Information: This study was funded by Dutch Heart Foundation (2013T084, Queen of Hearts program). AG was supported by EUTRAIN (European Translational tRaining for Autoimmunity & Immune manipulation Network), under funding from the 7th Framework program of the EU (FP7-PEOPLE-2011-ITN with the Marie Sklodowska-Curie grant agreement No. 289903). This study was also funded by the Swedish Research Council (K2013-65X-22345-01-3; 2015-02523), the Swedish Heart and Lung Foundation (20140078; 20140327; 20140427) and the Albert P?hlsson Foundation (FB2015-0116). HB is supported by the Swedish Heart and Lung Foundation (20130572). Funding Information: This study was funded by Dutch Heart Foundation (2013T084, Queen of Hearts program). AG was supported by EUTRAIN (European Translational tRaining for Autoimmunity & Immune manipulation Network), under funding from the 7th Framework program of the EU (FP7-PEOPLE-2011-ITN with the Marie Sklodowska-Curie grant agreement No. 289903). This study was also funded by the Swedish Research Council (K2013-65X-22345-01-3; 2015-02523), the Swedish Heart and Lung Foundation (20140078; 20140327; 20140427) and the Albert Påhlsson Foundation (FB2015-0116). HB is supported by the Swedish Heart and Lung Foundation (20130572). Publisher Copyright: © 2017 The Authors
(Peer reviewed)