Plasma extracellular vesicle SerpinG1 and CD14 levels are associated with MACE and MALE in patients undergoing femoral endarterectomy

Published:November 02, 2022DOI:
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      Objectives and design

      Plasma extracellular vesicles (EV) are an emerging source of biomarkers for diagnosis and prognosis of cardiovascular disease (CVD). Risk stratification for common adverse events such as Major Adverse Limb Event (MALE) and Major Adverse Cardiovascular Events (MACE) by an EV blood sample could improve healthcare management by individualizing drug therapy or by improving informed decision-making regarding revascularisations in patients with PAD. As such, we investigated the associations of plasma EV proteins with prospectively registered MALE and MACE in consecutive patients undergoing femoral endarterectomy.


      Using the Athero-Express biobank study, we measured four EV proteins (Cystatin C, CD14, Serpin C1 and Serpin G1) in the HDL subfraction isolated from plasma of 317 PAD patients undergoing arterial revascularization. Multivariable Cox proportional hazard regression was used to investigate the association between plasma EV-protein levels with MACE and MALE, in the three-year postoperative period.


      Most patients were treated for claudication (Fontaine II, 52.8%), although rest pain (Fontaine III, 30.1%) and ischemic wounds (Fontaine IV, 17.1%) were common in this cohort. Within three years, 51 patients died of which 25 due to CVD, 39 patients experienced a MACE, and 125 patients experienced a MALE. Multivariable regression models, based on statistically proven covariables and on literature, showed a significant association of Serpin G1 (HR 1.49 (95% CI 1.08 – 2.06) P = .016) and CD14 (HR 1.40 (1.03-1.90) P = .029) with MACE, and of Serpin G1 (HR 1.29 (1.07 – 1.57) P = .009) with MALE.


      Serpin G1 and CD14 plasma EV protein levels are associated with future MACE and MALE in patients with severe PAD.


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