Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes

Aims: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n\u2009=\u20092168) referred for coronary angiography, stable coronary artery disease (CAD) (n\u2009=\u200953), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n\u2009=\u200915) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30\u2009days (C-statistic 0.88 to 0.89, P\u2009=\u20090.001) and 1\u2009year (C-statistic 0.77 to 0.80, P\u2009<\u20090.001) comparable to high-sensitivity troponin T (30\u2009days: 0.88 to 0.89, P\u2009<\u20090.001; 1\u2009year: 0.77 to 0.79, P\u2009<\u20090.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n\u2009=\u2009362), Cyr61 was not associated with adverse outcome. Conclusion: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients