Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain

Background Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. Methods The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. Results Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99). Conclusion In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.