Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia

Aims: We explored the relationship between inflammation, renalase an anti- nflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). Methods and results: We used cardiac Rb-S2 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24 h of ED presentation and were analyzed for renalase and inflammatory markers including C-reactive protein, interleukins, interferon gamma, tumor necrosis factor, vascular endothelial growth factor, and metalloproteinases. Exclusions were age 30 years, myocardial infarction, hemodynamic instability, hypertensive crisis, heart failure or dialysis. Between 6/2014 and 11/2015, 80 patients undergoing PET/CT provided blood and were categorized as normal (1S%), CAD/CALC (27%) and CMD (55%). Median renalase values were highest in patients with CMD (5503 ng/ml; IQR 3070) compared to patients with normal flows (4266 nglml; IQR 1503; p 0.02) or CAD/CALC (4069 nglml IQR 1850; p 0.004). CMD patients had similar median values for inflammatory markers as normal patients (p > 0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% Cl 1.1-1.7, per 1000 ng/ml) after adjustment for smoking, family history, obesity and Framingham risk score. In a model for CMD diagnosis with Framingham risk score, typical angina history and CRP, renalase improved discrimination from C-statistic 0.60 (95% Cl 047, 0.73) to 070 (95% Cl, 0.59-0.32). Conclusion: We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials. (C) 2019 Elsevier B.V. All rights reserved.