Aisha Gohar1, Isabel Gonçalves2, Joyce Vrijenhoek3, Saskia Haitjema3, Ian van Koeverden3, Jan Nilsson4, Gert J de Borst5, Jean-Paul de Vries6, Gerard Pasterkamp7, Hester M den Ruijter3, Harry Björkbacka4, Saskia C A de Jager8. 1. Laboratory for Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Clinical Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands. 2. Experimental Cardiovascular Research Unit, and Cardiology (coronary) Clinic, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden. 3. Laboratory for Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands. 4. Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Sweden. 5. Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. 6. Department of Vascular Surgery, St. Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands. 7. Laboratory for Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory for clinical chemistry and haematology, University Medical Center Utrecht, Utrecht, the Netherlands. 8. Laboratory for Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: S.C.A.deJager@umcutrecht.nl.
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.
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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