Published 2017
| Version v1
Publication
Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes
Creators
- Klingenberg, Roland
- Aghlmandi, Soheila
- Liebetrau, Christoph
- Räber, Lorenz
- Gencer, Baris
- Nanchen, David
- Carballo, David
- Akhmedov, Alexander
- Montecucco, Fabrizio
- Zoller, Stefan
- Brokopp, Chad
- Heg, Dik
- Jüni, Peter
- Marti Soler, Helena
- Marques-Vidal, Pedro-Manuel
- Vollenweider, Peter
- Dörr, Oliver
- Rodondi, Nicolas
- Mach, François
- Windecker, Stephan
- Landmesser, Ulf
- von Eckardstein, Arnold
- Hamm, Christian W
- Matter, Christian M
- Lüscher, Thomas F
Contributors
Others:
- Klingenberg, Roland
- Aghlmandi, Soheila
- Liebetrau, Christoph
- Räber, Lorenz
- Gencer, Bari
- Nanchen, David
- Carballo, David
- Akhmedov, Alexander
- Montecucco, Fabrizio
- Zoller, Stefan
- Brokopp, Chad
- Heg, Dik
- Jüni, Peter
- Marti Soler, Helena
- Marques-Vidal, Pedro-Manuel
- Vollenweider, Peter
- Dörr, Oliver
- Rodondi, Nicola
- Mach, Françoi
- Windecker, Stephan
- Landmesser, Ulf
- von Eckardstein, Arnold
- Hamm, Christian W
- Matter, Christian M
- Lüscher, Thomas F
Description
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 = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) 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 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. Conclusion: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/887620
- URN
- urn:oai:iris.unige.it:11567/887620
Origin repository
- Origin repository
- UNIGE