Basmah Safdar1, Xiaojia Guo2, Caitlin Johnson3, Gail D'Onofrio3, James Dziura4, Albert J Sinusas5, Jeffrey Testani5, Veena Rao6, Gary Desir2. 1. Department of Emergency Medicine, New Haven, CT, United States of America. Electronic address: basmah.safdar@yale.edu. 2. Department of Internal Medicine (Section of Nephrology), New Haven, CT, United States of America. 3. Department of Emergency Medicine, New Haven, CT, United States of America. 4. Yale Center for Analytical Sciences, New Haven, CT, United States of America. 5. Department of Internal Medicine (Section of Cardiology), New Haven, CT, United States of America. 6. Department of Internal Medicine (Section of Nephrology), New Haven, CT, United States of America; Department of Internal Medicine (Section of Cardiology), New Haven, CT, United States of America.
Abstract
AIMS: We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). METHODS AND RESULTS: We used cardiac Rb-82 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 (18%), 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 ng/ml; IQR 1503; p = 0.02) or CAD/CALC (4069 ng/ml 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% CI = 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% CI 0.47, 0.73) to 0.70 (95% CI, 0.59-0.82). CONCLUSION: We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.
AIMS: We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). METHODS AND RESULTS: We used cardiac Rb-82 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 (18%), 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 ng/ml; IQR 1503; p = 0.02) or CAD/CALC (4069 ng/ml 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% CI = 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% CI 0.47, 0.73) to 0.70 (95% CI, 0.59-0.82). CONCLUSION: We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.
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