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, Baran; Nanchen, David; Carballo, David; Akhmedov, Alexander; Montecucco, Fabrizio; Zoller, Stefan; Brokopp, Chad E.; Heg, Dik; Jüni, Peter; Martí-Soler, Helena; Marques‐Vidal, Pedro; Vollenweider, Péter; Dörr, Oliver; Rodondi, Nicolas; Mach, François; Windecker, Stephan; Landmesser, Ulf; Eckardstein, Arnold von; Hamm, Christian W.; Matter, Christian M.; Lüscher, Thomas F.

doi:10.1093/eurheartj/ehx640

Cited by 49 publications

(51 citation statements)

References 48 publications

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“…The Special Programme University Medicine Acute Coronary Syndromes and Inflammation (SPUM‐ACS) cohort consists of patients with a primary diagnosis of ACS referred for an angiography to one of four Swiss academic centres (Bern, Geneva, Lausanne, and Zürich, NCT01000701) . For the analysis of plasma Lp(a) measurements, we extracted data from patients enrolled between December 2009 and October 2012, as in our previous publications . Inclusion criteria comprised of all females and males aged 18 years and older presenting within 5 days (preferably within 72 hour) after pain onset associated with either one of the following primary diagnoses: ST‐elevation myocardial infarction (STEMI), non‐ST‐elevation myocardial infarction (NSTEMI) or unstable angina.…”

Section: Methodsmentioning

confidence: 99%

“…11 For the analysis of plasma Lp(a) measurements, we extracted data from patients enrolled between December 2009 and October 2012, as in our previous publications. 11,12 Inclusion criteria comprised of all females and males aged 18 years and older presenting within 5 days (preferably within 72 hour) after pain onset associated with either one of the following primary diagnoses: ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina. Patients had to present symptoms compatible with angina pectoris (chest pain and dyspnoea) and fulfil at least one of the following criteria: (a) persistent ST-segment Arthemis Foundation (Fondation Dragon Bleu).…”

Section: Study Populationmentioning

confidence: 99%

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Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes

Gencer

Rigamonti

Nanchen

et al. 2019

Eur J Clin Investigation

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Background Minimal lipoprotein(a) [Lp(a)] target values are advocated for high‐risk cardiovascular patients. We investigated the prognostic value of Lp(a) in the acute setting of patients with acute coronary syndromes (ACS). Materials and methods Plasma levels of Lp(a) were collected at time of angiography from 1711 patients hospitalized for ACS in a multicentre Swiss prospective cohort. Associations between elevated Lp(a) ≥30 mg/dL (cut‐off corresponding to the 75th percentile of the assay) or Lp(a) tertiles at baseline, and major adverse cardiovascular events (MACE) at 1 year, defined as a composite of cardiac death, myocardial infarction or stroke, were assessed using hazard ratios (HR) and 95% confidence intervals (CI) adjusting for traditional cardiovascular risk factors (age, sex, smoking, diabetes, hypertension, low‐density lipoprotein cholesterol [LDL‐C], high‐density lipoprotein cholesterol [HDL‐C] and triglycerides. Results Lp(a) levels range between 2.5 and 132 mg/dL with a median value of 6 mg/dL and a mean value of 14.2 mg/dL. A total of 276 patients (23.0%) had Lp(a) plasma levels ≥30 mg/dL. Patients with elevated Lp(a) were more likely to be of female gender and to have higher levels of total cholesterol, LDL‐C, HDL‐C and triglycerides. Higher Lp(a) was associated with failure to reach the LDL‐C target <1.8 mmol/L at 1 year (HR 1.71, 95% CI 1.13‐2.58, P = 0.01). No association was found between elevated Lp(a) and MACE at 1 year (HR 1.05, 95% CI 0.64‐1.73), nor for Lp(a) tertiles (HR 0.82, 95% CI 0.52‐1.28, P > 0.20) or standardized continuous variables (0.98, 95% CI 0.82‐1.19 for each increase of standard deviation). Conclusions Our real‐world data suggest high Lp(a) levels at time of angiography are not predictive for cardiovascular outcomes in patients otherwise medically well controlled, but might be useful to identify patients who would not be on LDL‐C targets 1 year after ACS.

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Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes

Gencer

Rigamonti

Nanchen

et al. 2019

Eur J Clin Investigation

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“…Fold changes ≥ 2 or ≤ 0.5 are considered significant ADAMTS1 upregulation was shared by the two groups of patients. The secreted matricellular CYR61 protein was previously found highly expressed in remodeling atrial cardiomyocytes after myocardial infarction and proposed as an early prognostic biomarker of cardiac injury [89], while its mutations have been associated with ASD [90]. ADAMTS1 protein is a metalloprotease induced in the early phase of acute myocardial infarction playing an essential role in the repair of infarcted tissue and the development of heart fibrosis [91,92].…”

Section: Table 5 Relative Expression Of Genes Selectively Modulated Imentioning

confidence: 99%

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

et al. 2020

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Background: Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart diseases and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this procedure triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new potential biomarkers. Methods: Comparative transcriptome analysis of right atrium specimens collected from 10 ToF and 10 ASD patients was conducted before (Pre-CPB) and after (Post-CPB) corrective surgery. Total RNA isolated from each sample was individually hybridized on Affymetrix HG-U133 Plus Array Strips containing 38,500 unique human genes. Differences in the gene expression profiles and functional enrichment/network analyses were assessed using bioinformatic tools. qRT-PCR analysis was used to validate gene modulation. Results: Pre-CPB samples showed significant differential expression of a total of 72 genes, 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile

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“…Previous studies have found that some members of the CCN family are highly expressed in atherosclerotic plaques, contributing to the development of cardiovascular and cerebrovascular diseases and peripheral arterial diseases [5,6]. Cysteine-rich angiogenic inducer 61 (Cyr61), belongs to CCN family, is a 40 kD secreted extracellular matrix (ECM)-related signaling protein that can regulate cell proliferation, adhesion, differentiation and extracellular matrix production [7][8][9]. Cyr61 is maintained at a low level under normal conditions, but is usually elevated in various status of disease, such as colitis, rheumatoid arthritis, Graves' orbitopathy, diabetic retinopathy and atherosclerosis [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, inhibition of Cyr61 expression in carotid balloon injury rats can mitigated the proliferation of vascular smooth muscle cells, thereby attenuating vascular intimal hyperplasia [16]. Additionally, recent studies demonstrated that the Cyr61 levels were independently associated with the 30-day mortality in patients with acute heart failure (AHF) and coronary heart disease (CAD) [17], and could be a potential marker of myocardial ischemic injury and prognosis in patients with acute coronary syndrome (ACS) [9,18]. Till now, however, the link between circulating Cyr61 and PAD in diabetic patients has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Association of serum Cyr61 levels with peripheral arterial disease in patients with type 2 diabetes

Feng

Sun

et al. 2020

Preprint

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Background: The prevalence of peripheral artery disease (PAD) is obviously increased in diabetic patients. Existing evidences show that cysteine-rich angiogenic inducer 61 (Cyr61), a 40 kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 levels and atherosclerosis. However, the relationship between Cyr61 levels and PAD in type 2 diabetic patients remains obscure.Methods:. A total of 306 subjects with type 2 diabetes were recruited. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We analyzed Cyr61 serum levels by ELISA in patients with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD.Results: Out of the 306 patients enrolled in this study, 150 patients were free from PAD, while 156 had clinically significant PAD. In PAD patients, the prevalences of Fontaine classification stage II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend <0.001). The prevalence of PAD on the basis of severity increased with ascending Cyr61 quartiles (all P for trend <0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r=0.227, P=0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis.Conclusions: Our results demonstrated that Cyr61 was significantly increased in type 2 diabetic patients with PAD and that Cyr61 levels were positively associated with disease severity. It could be a promising biomarker and further studies are needed to assess its clinical utility.

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

Abstract: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

Cited by 49 publications

References 48 publications

Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes

Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

Association of serum Cyr61 levels with peripheral arterial disease in patients with type 2 diabetes

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