Dataset Information

Cysteine-Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes.

ABSTRACT: Background It remains unclear whether the novel biomarker cysteine-rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high-sensitivity Troponin T, hsCRP (high-sensitivity C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in patients with acute coronary syndromes. Methods and Results Patients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine - Acute Coronary Syndromes and Inflammation cohort. The primary/secondary end points were 30-day/1-year all-cause mortality and the composite of all-cause mortality or myocardial infarction as used in the GRACE risk score. Associations between biomarkers and outcome were assessed using log-transformed biomarker values and the GRACE risk score (versions 1.0 and 2.0). The incremental value of CCN1 beyond a reference model was assessed using Harrell's C-statistics calculated from a Cox proportional-hazard model. The P value of the C-statistics was derived from a likelihood ratio test. Among 2168 patients recruited, 1732 could be analyzed. CCN1 was the strongest single predictor of all-cause mortality at 30 days (hazard ratio [HR], 1.77 [1.31, 2.40]) and 1 year (HR, 1.81 [1.47, 2.22]). Adding CCN1 alone to the GRACE 2.0 risk score improved C-statistics for prognostic accuracy of all-cause mortality at 30 days (0.87-0.88) and 1 year (0.81-0.82) and when combined with high-sensitivity Troponin T, hsCRP, NT-proBNP for 30 days (0.87-0.91), and for 1-year follow-up (0.81-0.84). CCN1 also increased the prognostic value for the composite of all-cause mortality or myocardial infarction. Conclusions CCN1 predicts adverse outcomes in patients with acute coronary syndromes adding incremental information to the GRACE risk score, suggesting distinct underlying molecular mechanisms. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01000701.

SUBMITTER: Klingenberg R

PROVIDER: S-EPMC8751861 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:OBJECTIVE:We previously identified CYR61 as a histone deacetylase 5 (HDAC-5)-repressed gene in systemic sclerosis (SSc; scleroderma) endothelial cells (ECs). When overexpressed, cysteine-rich angiogenic inducer 61 (CYR-61) promoted angiogenesis in SSc ECs. This study was undertaken to examine the role of CYR-61 in fibrosis and determine the mechanisms involved in CYR-61-mediated angiogenesis in SSc. METHODS:Dermal ECs and fibroblasts were isolated from biopsy specimens from healthy subjects and patients with SSc. CYR-61 level was determined by quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. CYR-61 was overexpressed using a CYR61 vector or knocked down using small interfering RNA, and functional and mechanistic studies were then conducted in fibroblasts and ECs. RESULTS:Lower CYR61 messenger RNA levels were observed in dermal fibroblasts and ECs from SSc patients than in those from healthy controls. In SSc fibroblasts, overexpression of CYR-61 led to significant reduction in the expression of profibrotic genes, including COL1A1 (P = 0.002) and ACTA2 (P = 0.04), and an increase in the expression of matrix-degrading genes, including MMP1 (P = 0.002) and MMP3 (P =0.004), and proangiogenic VEGF (P = 0.03). The antifibrotic effect of CYR-61 was further demonstrated by delay in wound healing, inhibition of gel contraction, inactivation of the transforming growth factor β pathway, and early superoxide production associated with senescence in SSc fibroblasts. In SSc ECs, overexpression of CYR-61 led to increased production of vascular endothelial cell growth factor. The proangiogenic effects of CYR-61 were mediated by signaling through αvβ3 receptors and downstream activation of AMP-activated protein kinase, AKT, and the endothelial cell nitric oxide synthase/nitric oxide pathway system. CONCLUSION:CYR-61, which is epigenetically regulated by HDAC-5, is a potent antifibrotic and proangiogenic mediator in SSc. Therapeutic intervention to promote CYR-61 activity or increase CYR-61 levels might be of benefit in SSc.

Project description:BackgroundPublished data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.ObjectivesThe purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.MethodsFrom March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).ResultsIn 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).ConclusionsIn this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.

Dataset Information

Cysteine-Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets