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Circulating fibrocytes as predictors of adverse events in unstable angina.

ABSTRACT: Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of circulating fibrocytes predicts subsequent adverse events. We enrolled 55 subjects with UA, 18 with chronic stable angina, and 22 controls and correlated their concentration of circulating fibrocytes to clinical events (recurrent angina, myocardial infarction, revascularization, or death) over the subsequent year. Subjects with UA had a >2-fold higher median concentration of both total and activated fibrocytes compared with subjects with chronic stable angina and controls. In UA subjects, the concentration of total fibrocytes identified those who developed recurrent angina requiring revascularization (time-dependent area under the curve 0.85) and was superior to risk stratification using thrombolysis in myocardial infarction risk score and N-terminal pro B-type natriuretic peptide levels (area under the curve, 0.53 and 0.56, respectively, P < 0.001). After multivariable adjustment for thrombolysis in myocardial infarction predicted death, MI, or recurrent ischemia, total fibrocyte level was associated with recurrent angina (hazard ratio, 1.016 per 10,000 cells/mL increase; 95% confidence interval, 1.007-1.024; P < 0.001). Circulating fibrocytes are elevated in patients with UA and successfully risk stratify them for adverse clinical outcomes. Fibrocytes may represent a novel biomarker of outcome in this population.

SUBMITTER: Keeley EC

PROVIDER: S-EPMC4866880 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Circulating fibrocytes as predictors of adverse events in unstable angina.

Keeley Ellen C EC Schutt Robert C RC Marinescu Mark A MA Burdick Marie D MD Strieter Robert M RM Mehrad Borna B

Translational research : the journal of laboratory and clinical medicine 20160308

Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of c ...[more]

PMID: 27012475

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Project description:BackgroundStatin therapy plays a pivotal role in stabilizing the plaque for unstable angina (UA) patients although its mechanism(s) remains largely unexplored. Here we aim to identify microRNAs (miRNAs) mediating the protective effect of statins in UA patients.MethodsMiRNAs Array was carried out to compare the circulating whole blood miRNA profile of UA patients treated with (n?=?10) and without statin (n?=?10) and plasma miRNA profile UA patients treated with (n?=?5) and without statin (n?=?5). 22 whole blood miRNAs and 19 plasma miRNAs were found significantly upregulated in statin group. Targets of these miRNAs were predicted by algoritms: Targetscan, Miranda and Diana microT, then clustered according to functions and cell types by using the Database for Annotation, Visualization and Integrated Discovery (DAVID). To reveal the enriched function pathways in human atherosclerotic plaque, we analyzed microarray data from GEO database, Coronary atherosclerotic plaque (n?=?80); macrophages in ruptured plaque (n?=?11); carotid atheroma plaque (n?=?64); advanced carotid atherosclerotic plaque (n?=?29) using Reactome database. Integrated analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. In vulnerable plaque, additional immune system signaling was also targeted.ResultsThe data showed target genes regulated by these statin induced miRNAs majorly expressed in i) plaque macrophage and platelet, where they were involved in hemostasis process; ii) in monocyte to regulate NGF apoptosis; iii) and in endothelial cell function in Rho GTPase pathway. Integrate analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion.ConclusionsOur study suggest that statin induces the expression of multiple miRNAs in the circulation of UA patient, which play important roles by regulating signal pathways critical for the pathogenesis of UA.

Project description:Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20?mEq/L; QTc ?500?ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20?mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ? 500?ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

Dataset Information

Circulating fibrocytes as predictors of adverse events in unstable angina.

Publications

Circulating fibrocytes as predictors of adverse events in unstable angina.

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