Progression Of Acute Coronary Syndrome Research Articles

Evaluating the progression of acute coronary syndrome through the association of cardiac biomarkers with biochemical tests

Evaluating the progression of acute coronary syndrome through the association of cardiac biomarkers with biochemical tests

Ceramides and pro-inflammatory cytokines for the prediction of acute coronary syndrome: a multi-marker approach

BackgroundThere is a growing body of evidence supporting the significant involvement of both ceramides and pro-inflammatory cytokines in the occurrence and progression of acute coronary syndrome (ACS).MethodsThis study encompassed 216 participants whose laboratory variables were analysed using standardised procedures. Parameters included baseline serum lipid markers, comprising total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides (TGs), lipoprotein(a) (LPa), fasting blood glucose, B-natriuretic peptide and hypersensitive C-reactive protein. Liquid chromatography-tandem mass spectrometry measured the concentrations of plasma ceramides. Enzyme-linked immunosorbent assay quantified tumour necrosis factor-α (TNF-α), interleukin 6 (IL6) and IL8. The correlation between ceramides and inflammatory factors was determined through Pearson’s correlation coefficient. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression evaluated the diagnostic potential of models incorporating traditional risk factors, ceramides and pro-inflammatory cytokines in ACS detection.ResultsAmong the 216 participants, 138 (63.89%) were diagnosed with ACS. Univariate logistic regression analysis identified significant independent predictors of ACS, including age, gender, history of diabetes, smoking history, TGs, TNF-α, IL-6, ceramide (d18:1/16:0), ceramide (d18:1/18:0), ceramide (d18:1/24:0), ceramide (d18:1/20:0) and ceramide (d18:1/22:0). Multivariate logistic regression analysis revealed significant associations between gender, diabetes mellitus history, smoking history, LPa, IL-6, ceramide (d18:1/16:0) and ACS. Receiver operating characteristic analysis indicated that model 4, which integrated traditional risk factors, IL-6 and ceramide (d18:1/16:0), achieved the highest area under the curve (AUC) of 0.827 (95% CI 0.770–0.884), compared with model 3 (traditional risk factors and ceramide [d18:1/16:0]) with an AUC of 0.782 (95% CI 0.720–0.845) and model 2 (traditional risk factors and IL-6), with an AUC of 0.785 (95% CI 0.723–0.846) in ACS detection.ConclusionsIn summary, incorporating the simultaneous measurement of traditional risk factors, pro-inflammatory cytokine IL-6 and ceramide (d18:1/16:0) can improve the diagnostic accuracy of ACS.

Circulating mir-483-5p as a novel diagnostic biomarker for acute coronary syndrome and its predictive value for the clinical outcome after PCI

BackgroundMicroRNA (miRNA) plays a critical function in the progression of acute coronary syndrome (ACS) and is associated with major adverse cardiovascular events (MACEs) after undergoing percutaneous coronary intervention (PCI). This research was designed to probe the diagnostic accuracy of miR-483-5p in patients with ACS and its predictive value of MACEs.Methods118 patients with ACS (40 with unstable angina pectoris [UAP] and 78 with acute myocardial infarction [AMI]) and 75 healthy controls were enrolled. Serum miR-483-5p was detected in the subjects by reverse transcription-quantitative real-time PCR (RT-qPCR). ROC curve and logistic regression models were employed to estimate the diagnosis. Patients were monitored for 6 months after PCI to document the occurrence of MACEs. Kaplan-Meier survival was conducted to explore the predictive significance of miR-483-5p for the MACEs.ResultsSerum miR-483-5p levels were higher in ACS patients and associated with SYNTAX score and Gensini score. miR-483-5p was effective in identifying ACS patients from healthy individuals (AUC = 0.919) and AMI patients from ACS patients (AUC = 0.867), demonstrating a high diagnostic value, proven by logistic regression (OR = 9.664, 95%CI = 4.462–20.928, P < 0.001). The prevalence of MACEs during follow-up were 24.58%, and a higher prevalence of MACEs were observed in patients with elevated miR-483-5p (P = 0.01). miR-483-5p was also an effective predictor of MACE occurrence (HR = 5.955, 95%CI = 1.928–18.389, P = 0.002).ConclusionExpression of serum miR-483-5p can be utilized as a non-invasive marker for diagnosing ACS and predicting the onset of MACE after PCI.

Prevalence and prognosis of molecularly defined familial hypercholesterolemia in patients with acute coronary syndrome.

BackgroundFamilial hypercholesterolemia (FH) can elevate serum low-density lipoprotein cholesterol (LDL-C) levels, which can promote the progression of acute coronary syndrome (ACS). However, the effect of FH on the prognosis of ACS remains unclear.MethodsIn this prospective cohort study, 223 patients with ACS having LDL-C ≥ 135.3 mg/dL (3.5 mmol/L) were enrolled and screened for FH using a multiple-gene FH panel. The diagnosis of FH was defined according to the ACMG/AMP criteria as carrying pathogenic or likely pathogenic variants. The clinical features of FH and the relationship of FH to the average 16.6-month risk of cardiovascular events (CVEs) were assessed.ResultsThe prevalence of molecularly defined FH in enrolled patients was 26.9%, and coronary artery lesions were more severe in patients with FH than in those without (Gensini score 66.0 vs. 28.0, respectively; P < 0.001). After lipid lowering, patients with FH still had significantly higher LDL-C levels at their last visit (73.5 ± 25.9 mg/dL vs. 84.7 ± 37.1 mg/dL; P = 0.013) compared with those without. FH increased the incidence of CVEs in patients with ACS [hazard ratio (HR): 3.058; 95% confidence interval (CI): 1.585–5.900; log-rank P < 0.001].ConclusionFH is associated with an increased risk of CVEs in ACS and is an independent risk factor for ACS. This study highlights the importance of genetic testing of FH-related gene mutations in patients with ACS.

Models of Ischaemia and Ischaemia-Reperfusion of the Myocardium in an Experiment on Rats with Regard to of Novel Concepts of Progression of Acute Coronary Syndrome

Models of Ischaemia and Ischaemia-Reperfusion of the Myocardium in an Experiment on Rats with Regard to of Novel Concepts of Progression of Acute Coronary Syndrome

Models of Ischaemia and Ischaemia– Reperfusion of the Myocardium in an Experiment on Rats with Regard to of Novel Concepts of Progression of Acute Coronary Syndrome

Purpose: Animal models of cardiovascular diseases provide us with important insights regarding the pathophysiology and progression of cardiovascular diseases and are instrumental in evaluating new pharmacological agents. To date, different models that focus on various aspects of acute coronary syndrome have been proposed. In this context, the primary aim of the present study was to investigate the models of total myocardial ischaemia and ischaemia–reperfusion from the standpoint of modern concepts of the development and progression of acute coronary syndrome. Patients and methods: The in vivo study involved 70 sexually mature male Wistar rats. Laboratory animals were divided into two groups of total myocardial ischaemia (n = 30) and myocardial ischaemia–reperfusion (n = 30). A group of intact rats (n = 10) was used to confirm that all lesions were caused directly by irreversible ischaemia or ischaemic–reperfusion syndrome (IRS) due to ligation of the left coronary artery.ResultsThe main histological, echocardiographic, biochemical changes in the myocardium in models of acute coronary syndrome are described. The main marker indicators are highlighted. Conclusion:The available range of experimental techniques allows the adaptation of the universally acknowledged model of acute coronary syndrome for the study of IRS, which in turn can be used to study the mechanisms of this pathological process and for preclinical studies of new treatment modalities influencing the cardiovascular system.

Interleukin-9-secreting CD4+ T cells regulate CD8+ T cells cytotoxicity in patients with acute coronary syndromes.

T cells play vital roles in the development and progression of acute coronary syndromes (ACS), including cytotoxicity mediated by CD8+ T cells and immunoregulatory activity mediated by CD4+ T cells. Interleukin (IL)-9-secreting CD4+ T cells (Th9 cells) were recently found to be involved in the onset of ACS. We investigated regulatory role of Th9 cells to CD8+ T cells in patients with stable angina pectoris, unstable angina pectoris, and acute myocardial infarction (AMI). Circulating Th9 cells percentage, plasma IL-9 level, and PU.1 mRNA relative level was up-regulated in AMI patients compared with controls. There was no significant difference of IL-9-secreting CD8+ T cells percentage among groups. CD8+ T cells from AMI patients revealed increased cytotoxicity than those from controls, which presented as enhanced cytotolytic activity to target cells, increased interferon-γ and tumor necrosis factor-α secretion, elevated perforin and granzyme B production, and reduced programmed death-1 and cytotoxic T lymphocyte-associated protein 4. IL-9 stimulation did not affect proliferation, but promoted CD8+ T-cell cytotoxicity from both controls and AMI patients. IL-9-secreting CD4+ T cells were enriched in CD4+ CCR4- CCR6- CXCR3- cells. The enhancement of CD8+ T-cell cytotoxicity induced by CD4+ CCR4- CCR6- CXCR3- cells was dependent on IL-9 secretion. The present results indicated that up-regulation of IL-9-secreting CD4+ T cells may contribute to pathogenesis of AMI through enhancement of CD8+ T-cell cytotoxicity.

Premature CD4+ T Cells Senescence Induced by Chronic Infection in Patients with Acute Coronary Syndrome.

Acquired immune responses mediated by CD4+ T cells contribute to the initiation and progression of acute coronary syndrome (ACS). ACS patients show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. This study aimed to investigate the role of premature CD4+ T cells senescence in ACS and the underlying mechanism. We compared the immunological status of 25 ACS patients, 15 young healthy individuals (C1), and 20 elderly individuals with absence of ACS (C2). The percentages of CD4+ T lymphocyte subsets (including naïve, regulatory, memory and effector T cells) in peripheral blood were analyzed. In ACS patients, a significant expansion of CD4+CD28null effector T cells and a decline of CD4+CD25+CD62L+Treg cells were observed. In addition, patients with ACS showed an accelerated loss of CD4+CD45RA+CD62L+ naïve T cells and a compensatory increase in the number of CD4+CD45RO+ memory T cells. ACS patients demonstrated no significant difference in frequency of T cell receptor excision circles (TRECs) compared to age-matched healthy volunteers. The expression of p16Ink4a was increased while CD62L was decreased in CD4+CD28null T cells of ACS patients. Compared to healthy donors, ACS patients demonstrated the lowest telomerase activity in both CD4+CD28+and CD4+CD28null T cells. The serum levels of C-reactive protein, Cytomegalovirus IgG, Helicobactor pylori IgG and Chlamydia pneumonia IgG were significantly higher in ACS patients. The results suggested that the percentage of CD4+ T cell subpopulations correlated with chronic infection, which contributes to immunosenescence. In conclusion, chronic infection induced senescence of premature CD4+T cells, which may be responsible for the development of ACS.

A Novel Concept in the Progression of Acute Coronary Syndrome: Acute Coronary Continuum (ACC)

A Novel Concept in the Progression of Acute Coronary Syndrome: Acute Coronary Continuum (ACC)

Analysis of long non‑coding RNA expression profiles identifies functional lncRNAs associated with the progression of acute coronary syndromes

It has been demonstrated that long non-coding RNAs (lncRNAs) are important in the gene regulatory network and their dysregulated expression has been implicated in cardiovascular disease. However, little is known regarding lncRNA expression patterns and their function in the progression of acute coronary syndromes (ACSs). In the present study, the expression profiles of lncRNAs from 52 patients with ACS were analyzed by re-annotating existing microarray data. The lncRNA expression profiles in the two distinct clinical entities of ACS, myocardial infarction (MI) and unstable angina (UA), were examined. Out of the 2,332 lncRNAs assessed, it was identified that 18 lncRNAs were upregulated and 35 lncRNAs were downregulated in patients with MI compared to those with UA. Furthermore, the expression profiles of patients with ACS were compared at different time points and significantly altered lncRNA expression was observed during the progression of ACS. A total of 7 candidate lncRNA biomarkers were identified and an lncRNA-based classifier was developed to predict MI risk based on the expression data of the 7 lncRNAs using random forest and support vector machine strategies. This achieved a classification accuracy of 90.38% with a sensitivity of 100% and a specificity of 68.75%. Additionally, functional analysis suggested that these 7 lncRNAs may be involved in known MI-associated biological processes and pathways.

Potential Harmful Effects of PM2.5 on Occurrence and Progression of Acute Coronary Syndrome: Epidemiology, Mechanisms, and Prevention Measures.

The harmful effects of particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) and its association with acute coronary syndrome (ACS) has gained increased attention in recent years. Significant associations between PM2.5 and ACS have been found in most studies, although sometimes only observed in specific subgroups. PM2.5-induced detrimental effects and ACS arise through multiple mechanisms, including endothelial injury, an enhanced inflammatory response, oxidative stress, autonomic dysfunction, and mitochondria damage as well as genotoxic effects. These effects can lead to a series of physiopathological changes including coronary artery atherosclerosis, hypertension, an imbalance between energy supply and demand to heart tissue, and a systemic hypercoagulable state. Effective strategies to prevent the harmful effects of PM2.5 include reducing pollution sources of PM2.5 and population exposure to PM2.5, and governments and organizations publicizing the harmful effects of PM2.5 and establishing air quality standards for PM2.5. PM2.5 exposure is a significant risk factor for ACS, and effective strategies with which to prevent both susceptible and healthy populations from an increased risk for ACS have important clinical significance in the prevention and treatment of ACS.

GW26-e3819 Association of matrix metalloproteinase-1 -519A/G polymorphism with acute coronary syndrome: a meta-analysis

Matrix metalloproteinase-1 (MMP-1) has been demonstrated to play an important role in the development and progression of acute coronary syndrome (ACS). Recent studies have shown that MMP-1 -519 A/G (rs1144393) polymorphism is associated with the susceptibility to ACS. However, published studies

Circulating miR-323-3p and miR-652: Candidate markers for the presence and progression of acute coronary syndromes

BackgroundThe prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5years of follow-up. MethodsAn initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~30days post-ACS) and at 4 and 12months post-ACS, and compared with 100 controls. ResultsIn the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12months; whereas miR-27b fell to control levels by 4months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). ConclusionsOur study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.

Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model

Acute coronary syndrome is a serious medical emergency. It occurs when an atherosclerotic plaque ruptures, leading to thrombus formation within a coronary artery. Previous studies have shown that T cells are involved in the initiation and progression of acute coronary syndrome. CD4(+)CD28(null) T lymphocytes increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3 blockers can suppress the function of these cells in vitro by preventing exocytosis of their cytoplasmic granules. The purpose of this study was to investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the potential mechanism for this effect. Plasma lipids, interferonγ, CRP, CD4(+)CD28(null) T cells, and perforin were increased and unstable atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3 potassium channel via PAP-1 administration decreased perforin levels and prevented plaque formation but had no effect on the other changes seen in this AS model. These findings suggest that the small molecule, voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model, most likely by inhibiting the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells.

Early Time-Dependent Dynamic Changes of TBET and GATA3 mRNA Expressions in Patients with Acute Coronary Syndrome

Background. T-box expressed in T cells (TBET) and guanine adenine thymine adenine sequence-binding protein 3 (GATA3) play important roles in the differentiation of Th1 and Th2 subsets, which contributes to the progression of acute coronary syndrome (ACS). Objective. This study aimed to investigate the temporal change of TBET/GATA3 mRNA ratio in ACS. Methods. Thirty-three patients suspected of ACS with symptom onset within 24 hours were recruited. Blood samples were taken after arrival at the emergency department and at hourly intervals until the 6th hour. The mRNA expressions of TBET and GATA3 were quantified by a real-time RT-qPCR. Results. The TBET/GATA3 mRNA ratio was elevated dramatically in patients with acute myocardial infarction (AMI) and exhibited biphasic M-shaped release kinetics with two distinct peaks. The ratio was elevated 2 hours after symptom onset, dropped to the lowest level at 10 hours, and rose to the second peak at 14 hours. A similar biphasic M-shaped curve was observed in AMI patients with blood samples taken prior to any intervention. Conclusions. The TBET/GATA3 mRNA ratio was elevated in AMI patients throughout most of the first 20 hours after symptom onset. The biphasic M-shaped release kinetics was more likely to reflect pathophysiological changes rather than treatment effects.

Circulating leukocyte TBET and GATA3 mRNA in patients with acute coronary syndrome

Th1/Th2 imbalance contributes to the initiation and progression of acute coronary syndrome (ACS) [1–6]. The relative expression of two upstream transcription factors, T-box expressed in T cells (TBET) and guanine adenine thymine adenine sequence-binding protein 3 (GATA3), resulting in a swing in the Th-1/Th-2 pendulum has been implicated in immunological diseases and may provide better diagnostic and prognostic information than downstream cytokines. TBET promotes Th1 lineage commitment [7] and maintains the Th1 mediated immune response, which fosters macrophage activation, infiltration and the resulting ACS [8].

Prognostic value of combination of heart‐type fatty acid‐binding protein and ischemia‐modified albumin in patients with acute coronary syndromes and normal troponin T values

Recent studies have suggested that heart-type fatty acid-binding protein (H-FABP) may detect ongoing myocardial damage involved in the progression of acute coronary syndromes (ACS). This study was prospectively designed to examine whether the combination of H-FABP, a marker for ongoing myocardial damage, and ischemia-modified albumin (IMA), a marker for myocardial ischemia, would effectively diagnose patients with ACS. H-FABP values above 1.5 microg/l can be correctly measured via an ELISA and 6 microg/l is the currently used cut-off value (1-3). We measured serum H-FABP and IMA of 108 patients on admission within 12 hr after onset of chest pain and normal troponin T. serum samples from ACS group (n=82) had decreased capacity of ACB [64 (61-67) U/ml] compared with non-ACS ischemic chest pain group (n=26) samples [75 (71-78) U/ml] (P<0.05). The combination of IMA and H-FABP usually had better sensitivity [96.3% (92.2-100%)] (P<0.05) and accuracy [92.6 (87.7-97.5%)] (P<0.05) than when individually used. Thus, the combination of H-FABP and IMA measurements after initiation of chest pain may be highly effective for risk stratification in patients with ACS and normal cardiac troponin T.

129: Hypoadiponectinemia and increased C-reactive protein related to the progression of acute coronary syndrome

129: Hypoadiponectinemia and increased C-reactive protein related to the progression of acute coronary syndrome

Effect of Coronary Percutaneous Revascularization on Interferon-γ and Interleukin-10 Producing CD4+ T Cells during Acute Myocardial Infarction

T lymphocytes play an important role in the induction and progression of acute coronary syndromes (ACS). To gain insight into how different T cell subsets can influence ACS, we analyzed the frequencies of circulating CD4+ T cells producing either pro-inflammatory interferon(IFN)-gamma or anti-inflammatory interleukin (IL)-10 in subjects presenting with ST-elevation myocardial infarction (STEMI). The effect of coronary bare metal (BS) and paclitaxel-eluting stent (PES) on the balance between CD4+IFN-gamma+ and CD4+IL-10+ lymphocytes was also investigated. Peripheral blood mononuclear cells (PBMC) were isolated from 38 consecutive patients with STEMI before and 48 hrs or 6 days after implantation of either BS or PES. Twenty patients with no history of coronary artery disease were included as basal controls. PBMC were stimulated in vitro with anti-CD3/anti-CD28 monoclonal antibodies, and CD4+IFN- gamma+ or CD4+IL-10+ T cells were detected by flow cytometry intracellular staining. The frequency of peripheral CD4+IL-10+ T cells was significantly higher in STEMI patients as compared with controls. Conversely, the frequency of CD4+IFN-gamma+ T lymphocytes did not differ between STEMI and subjects without history of coronary artery disease. Six days after the revascularization procedure, the percentage of CD4+IL-10+ T cells was significantly decreased in BS but not in the PES group, whereas the relative percentage of CD4+IFN-gamma+ T lymphocytes were diminished in both groups as compared with baseline levels. Our data indicate that STEMI is associated with a peripheral expansion of CD4+IL-10+ T lymphocytes, and that primary coronary revascularization with implantation of either BS or PES is followed by a reduction in circulating CD4+IFN-gamma+ T lymphocytes. PES implantation, however, appears to inhibit the relative decrease of the IL-10 producing lymphocyte as observed in BS implanted patients, shifting the balance between pro-inflammatory and anti-inflammatory T cell populations in favor of the latter.

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.