Plasma Extracellular Vesicle Serpin G1 and CD14 Levels are Associated with Major Adverse Cardiovascular Events and...

Area of Science:

• Cardiovascular Research
• Biomarker Discovery
• Vascular Biology

Background:

• Plasma extracellular vesicles (EVs) are increasingly recognized as valuable biomarkers for cardiovascular disease (CVD) diagnosis and prognosis.
• Risk stratification for adverse events like major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in peripheral artery disease (PAD) patients is crucial for effective management.
• Individualized therapy and informed decision-making regarding revascularization procedures can be enhanced by reliable predictive biomarkers.

Purpose of the Study:

• To investigate the association between plasma EV proteins and prospectively registered MALE and MACE in patients undergoing femoral endarterectomy.
• To identify specific EV proteins that can serve as predictive biomarkers for adverse cardiovascular and limb events in severe PAD.
• To explore the potential of EV protein analysis for risk stratification in PAD patients.

Main Methods:

• The Athero-Express biobank study cohort of 317 PAD patients undergoing arterial revascularization was utilized.
• Four EV proteins (Cystatin C, CD14, Serpin C1, and Serpin G1) were quantified in the high-density lipoprotein (HDL) subfraction of plasma.
• Multivariable Cox proportional hazard regression analysis was employed to assess the association between EV protein levels and MACE/MALE within three years post-operation.

Main Results:

• The study cohort predominantly consisted of patients with claudication (Fontaine II, 52.8%), but also included those with rest pain (Fontaine III, 30.1%) and ischemic wounds (Fontaine IV, 17.1%).
• Within three years, 51 patients died (25 from CVD), 39 experienced MACE, and 125 experienced MALE.
• Multivariable regression models revealed significant associations of Serpin G1 (HR 1.49) and CD14 (HR 1.40) with MACE, and Serpin G1 (HR 1.29) with MALE.

Conclusions:

• Plasma EV protein levels of Serpin G1 and CD14 are significantly associated with the occurrence of future MACE and MALE in patients with severe PAD.
• These findings suggest that Serpin G1 and CD14 hold potential as predictive biomarkers for stratifying risk in PAD patients.
• Further research can explore the clinical utility of these EV proteins in guiding treatment decisions and improving outcomes for individuals with severe PAD.