Circulating GDF-15 Levels Predict Future Secondary Manifestations of Cardiovascular Disease Explicitly in Women but not Men with Atherosclerosis

• Published in: International journal of cardiology Vol. 241; pp. 430 - 436
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2017
• Subjects: Aged; Atherosclerosis; Biomarker; Biomarkers - blood; Cardiac and Cardiovascular Systems; Cardiovascular; Cardiovascular Diseases - blood; Cardiovascular Diseases - diagnosis; Carotid Artery Diseases - blood; Carotid Artery Diseases - diagnosis; Clinical Medicine; Cohort Studies; Disease Progression; Female; Follow-Up Studies; GDF-15; Growth Differentiation Factor 15 - blood; Humans; Kardiologi; Klinisk medicin; Longitudinal Studies; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Prognosis; Secondary outcome; Sex Characteristics; Women; atherosclerosis; secondary outcome; biomarker; prognosis; GDF-15; women; Women; Biomarker; Prognosis; Secondary outcome; Atherosclerosis
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2017.03.101

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 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.