Plasma extracellular vesicle proteins are associated with stress-induced myocardial ischemia in women presenting with chest pain

Mirthe Dekker,Nathalie Timmerman,Ingrid E M Bank,Gerard Pasterkamp,Diederick E Grobbee,Robbert J De Winter,Christian Mueller,Joelle Van Bennekom,A Mosterd,Joan E Walter,Raymond M Schiffelers,Leo Timmers,Dominique P V De Kleijn,Max J M Silvis,Farahnaz Waissi,A H Schoneveld

doi:10.1038/s41598-020-69297-0

Abstract

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. Currently, no blood test is available. Plasma extracellular vesicles (EV) are emerging as potential biomarker source. We therefore aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. We analyzed 450 patients suspected for stable IHD who were referred for 82Rb PET/CT in the outpatient clinic. Blood samples were collected before PET/CT and plasma EVs were isolated in 3 plasma subfractions named: TEX, HDL, LDL. In total 6 proteins were quantified in each of these subfractions using immuno-bead assays. CD14 and CystatinC protein levels were independent significant predictors of stress-induced ischemia in the LDL and the HDL subfraction and SerpinC1 and SerpinG1 protein levels in the HDL fraction. Subgroup-analysis on sex revealed that these associations were completely attributed to the associations in women. None of the significant EV proteins remained significant in men. Plasma EV proteins levels are associated with the presence of stable IHD in females presenting with chest pain. This finding, if confirmed in larger cohort studies could be a crucial step in improving diagnostic assessment of women with suspected IHD.

Highlights

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females
We investigated if plasma extracellular vesicles (EV) protein levels in 3 subfractions are associated with stress-induced ischemia, in patients presenting with chest pain in the outpatient clinic
Univariable analysis showed significant differences between cases and controls for Serpin C1 (SC1) High-Density Lipid particles (HDL) (odds ratio (OR) 1.31, 95% CI: 1.04–1.66), CD14 HDL, CD14 Lipid particles (LDL), Serpin G1 (SG1) HDL, Cystatin C (CC) HDL, CC LDL

Summary

Introduction

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. We aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. A recently performed costeffectiveness analysis of non-invasive imaging showed a prevalence of obstructive coronary artery disease (CAD) in only 25% of suspected stable IHD patients[5]. Another concern that merit consideration in IHD is the evolving knowledge regarding sex differences in pathophysiology, symptoms, diagnostic test performance, and prognosis. We investigated if plasma EV protein levels in 3 subfractions are associated with stress-induced ischemia, in patients presenting with chest pain in the outpatient clinic

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Results

Conclusion