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

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 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. 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 > 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). Conclusion We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.

The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction

“…This is, truly, the very first study to review and confirm the prognostic potential of renalase for ischemia, regarding the ejection fraction stratification. Likewise, impressive evidence has recently implicated renalase as a possible biomarker for ischemia ( 5 , 14 , 16 – 18 , 25 – 27 ). The obtained findings may add considerably to the growing body of literature in this field.…”

“…Moreover, substantial evidence showed that functional polymorphisms of the renalase gene were associated with cardiac hypertrophy in patients with aortic stenosis ( 8 ) and an increased risk of CAD in the general population ( 9 ) and in hemodialyzed patients ( 10 ), patients with hypertension and associated CAD ( 11 ), patients with unstable angina pectoris and concomitant metabolic syndrome ( 12 ), and in patients with stable CAD, presenting with cardiac hypertrophy, ventricular dysfunction, and inducible ischemia ( 13 ). Moreover, renalase has been suggested as a prognostic biomarker for ischemia in patients with acute coronary microvascular dysfunction ( 14 ) and as a predictor for all-cause mortality in chronic kidney disease ( 15 ).…”

Role of Inflammation in Coronary Epicardial and Microvascular Dysfunction

“…Patients with acute chest pain who were found to have CMD, as assessed by reduced PET-derived CFR, but no evidence of CAD had elevated levels of serum renalase, an anti-inflammatory protein released from the heart and kidneys in response to acute ischaemic stress. [ 51 ] Of note, these patients had similar concentrations of serum inflammatory markers (CRP, TNF-α, vascular endothelial growth factor, IL-1β, IL-6 and metalloproteinases) as control patients. [ 51 ] These findings imply the dynamic nature of the inflammatory response to an acute ischaemic insult compared with chronic coronary syndrome.…”

“…[ 51 ] Of note, these patients had similar concentrations of serum inflammatory markers (CRP, TNF-α, vascular endothelial growth factor, IL-1β, IL-6 and metalloproteinases) as control patients. [ 51 ] These findings imply the dynamic nature of the inflammatory response to an acute ischaemic insult compared with chronic coronary syndrome. [ 51 ]…”

“…[ 51 ] These findings imply the dynamic nature of the inflammatory response to an acute ischaemic insult compared with chronic coronary syndrome. [ 51 ]…”