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

Gohar A, Gonçalves I, Vrijenhoek J, Haitjema S, van Koeverden I, Nilsson J, de Borst GJ, de Vries JP, Pasterkamp G, den Ruijter HM, Björkbacka H, de Jager SCA

Int. J. Cardiol. 241 (-) 430-436 [2017-08-15; online 2017-03-22]

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. 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. 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. 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.

Clinical Biomarkers [Service]

PLA and Single Cell Proteomics [Service]

PubMed 28389123

DOI 10.1016/j.ijcard.2017.03.101

Crossref 10.1016/j.ijcard.2017.03.101

pii: S0167-5273(16)33754-8

Publications 7.0.1