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

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; ... (2017). Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes. European Heart Journal, 38(47), pp. 3493-3502. Oxford University Press 10.1093/eurheartj/ehx640

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern

UniBE Contributor:

Aghlmandi, Soheila; Räber, Lorenz; Heg, Dierik Hans; Rodondi, Nicolas and Windecker, Stephan

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0195-668X

Publisher:

Oxford University Press

Language:

English

Submitter:

Nadia Biscozzo

Date Deposited:

09 Jan 2018 15:59

Last Modified:

10 Jan 2018 08:32

Publisher DOI:

10.1093/eurheartj/ehx640

PubMed ID:

29155984

Uncontrolled Keywords:

Acute coronary syndromes Biomarker Risk stratification

BORIS DOI:

10.7892/boris.107396

URI:

https://boris.unibe.ch/id/eprint/107396

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