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

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d6201391e214">Aims</h5> <p id="P1">We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d6201391e219">Methods and Results</h5> <p id="P2">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 hours 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. </p> <p id="P3">Between 6/2014-11/2015, 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 &gt; 0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% CI= 1.1-1.7, per 1,000 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). </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d6201391e226">Conclusion</h5> <p id="P4">We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials. </p> </div>