Biomarker For Acute Coronary Syndrome Research Articles

Soluble urokinase plasminogen activator receptor as a long-term prognostic biomarker in acute coronary syndromes

Purpose: The aim of our study was to analyse the long-term prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in the setting of an acute coronary syndrome (ACS).Methods: We included 340 patients with an ACS who underwent coronary angiography and plasma suPAR concentration was measured. Patients were classified into low suPAR concentrations (<2.6 ng/mL) and high suPAR concentrations (≥2.6 ng/mL) and long-term events were evaluated. suPAR prognostic value was assessed beyond a clinical model that included age, GRACE score, estimated glomerular filtration rate, cardiac troponin-I peak and left ventricular ejection fraction <40%.Results: Higher suPAR concentrations were associated with an increased prevalence of cardiovascular risk factors. After multivariate adjustment, suPAR ≥2.6 ng/mL were independently associated with an increased risk of all-cause death (HR 2.3; 95%CI 1.2–4.4; p = .017), major adverse cardiovascular events (MACE) (HR 1.7; 95%CI 1.1–2.5; p = .020) and heart failure (HR 4.1; 95%CI 1.3–12.6; p = .015), but not with myocardial infarction. For long-term all-cause death significant improvement of reclassification and discrimination were seen after addition of suPAR to a clinical model.Conclusions: In the setting of an ACS, suPAR is associated with long-term all-cause death, heart failure and MACE, and provides incremental prognostic value beyond traditional risks factors.

Noncoding RNAs as Biomarkers for Acute Coronary Syndrome.

Acute coronary syndrome (ACS), consisting of acute myocardial infarction and unstable angina, is the most dangerous and fatal form of coronary heart disease. Acute coronary syndrome has sudden onset and rapid development, which may lead to malignant life-threatening conditions at any time. Therefore, early detection and diagnosis are critical for patients with ACS. Recent studies have found that noncoding RNA is of great significance in the diagnosis and treatment of cardiovascular diseases. In this review, we summarized recent data on circulating noncoding RNAs (including microRNA, long noncoding RNA, and circular RNA) as diagnostic and prognostic markers in ACS including acute myocardial infarction and unstable angina. Specifically, microRNAs (miRNAs) as diagnostic markers are divided into three types: miRNAs of increased expression in ACS, miRNAs of decreased expression in ACS, and miRNAs of contradictory expression in ACS. Moreover, we described these miRNAs of increased expression in ACS based on miRNAs family. This review may result in a great guidance of noncoding RNAs as biomarkers for ACS in clinical practice.

MicroRNA-145 is involved in endothelial cell dysfunction and acts as a promising biomarker of acute coronary syndrome

BackgroundAcute coronary syndrome (ACS) is a serious type of cardiovascular diseases. This study aimed to investigate the expression patterns and clinical value of microRNA-145 (miR-145) in ACS patients, and further uncover the function of miR-145 in ACS rats.MethodsQuantitative real-time PCR was used to estimate the expression of miR-145. Diagnostic value of miR-145 was evaluated, and its correlation with endothelial injury marker (vWF and H-FABP) and pro-inflammatory cytokines (IL-6 and TNF-α) was analyzed. Coronary artery ligation was adopted to construct the ACS rat model, and the effects of miR-145 on endothelial injury, inflammation and vascular endothelial cells (VECs) biological function were examined.ResultsDownregulated expression of miR-145 was found in the ACS serum samples compared with the healthy controls. The expression of miR-145 was proved to be a diagnostic biomarker and negatively correlated with vWF, H-FABP, IL-6 and TNF-α. The similar serum expression trends of miR-145 in ACS patients were also observed in the ACS rats, and the overexpression of miR-145 could decrease the elevated vWF, H-FABP, IL-6 and TNF-α in the animal model. Moreover, the upregulation of miR-145 in VECs led to promoted proliferation and migration. The bioinformatics prediction data and luciferase report results indicated that FOXO1 was a direct target of miR-145.ConclusionsIn conclusion, it was hypothesized that serum decreased expression of miR-145 may serve as a potential diagnostic biomarker in ACS patients. Overexpression of miR-145 may improve the endothelial injury and abnormal inflammation through targeting FOXO1, indicating that miR-145 serves as a candidate therapeutic target of ACS.

Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events

Plasma trimethylamine N-oxide (TMAO) is associated with coronary atherosclerotic plaque and cardiovascular disease risk, but associations between gut microbes in acute coronary syndrome (ACS) and post-ST-segment elevation myocardial infarction (post-STEMI) events are unknown. We investigated associations between gut microbial taxa and systemic TMAO levels and the possible TMAO contribution to incident post-STEMI cardiovascular events. Patients and Methods. A total of 60 patients, including 30 with unstable angina pectoris (UAP), 30 post-STEMI and 30 healthy controls, were enrolled from June to November 2017. Metagenomic sequencing was performed and TMAO and IL-6 were detected. Results. Minimal discriminators of gut microbial taxa (top 40) distinguished ACS patients from controls. Serum TMAO levels were positively associated with increased abundance of Aerococcaceae, Ruminococcaceae_UCG.005, Ruminococcaceae_UCC.014 and X. Eubacterium_fissicatena, and decreased abundance of Lachnospiraceae_FCS020 (P < 0.05). Elevated serum TMAO levels correlated independently with ACS (P < 0.05). Risk stratification for incident major adverse cardiovascular events (MACE) improved at one year in patients with serum TMAO levels ≦2.19 µM. Serum interleukin-6 levels were not significantly increased in patients with ACS and post-STEMI MACE. Conclusions. ACS and incident post-STEMI MACE may be associated with the gut bacteria choline metabolite TMAO. The specific gut microbial taxa identified in association with serum TMAO levels may be potential predictive biomarkers for accurate diagnosis of ACS onset.

The thromboelastography G parameter as a potential biomarker of acute coronary syndrome

The most prominent event that defines acute coronary syndrome (ACS) is the formation of an intra-arterial thrombus, usually resulting from activation of platelet and fibrinogen at the ruptured plaque. Usually, conventional coagulation tests (CCTs) are used to estimate the hemostatic properties of patients. However, CCTs have significant limitations because they each assess individual aspects of the coagulation cascade, which is a complex multifaceted process. And CCTs are performed with platelet-poor plasma, while the contribution of platelets to clot formation is not measured. In contrast, thromboelastography (TEG) is a test for global hemostasis with whole blood, from the beginning of coagulation through clot formation to the ending with fibrinolysis. The aim of this study was to investigate whether TEG parameters could be surrogate biomarkers of thrombus formation process and diagnosis of ACS. Receiver operating characteristic（ROC）curve was used to evaluate the diagnosis performance of each index. Logistic regression analysis was utilized to define the independent risk factors of ACS. The results showed that the shear elastic modulus parameter (G) was an independent diagnostic indicator for ACS (odds ratio [OR], 2.600; 95% confidence interval [CI], 2.035–3.322). The area under ROC curve of G was 0.866. The optimal cut-off value for the diagnosis of ACS was 10.55 dyne/cm2, while the sensitivity was 66.2% and the specificity was 92.4%. In conclusion, G could be used as an optimal indicator of activation of platelet and fibrinogen, which is eligible to be a useful biomarker for early diagnosis of ACS.

Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease.

The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).

Role of Cardio-Specific Micro-RibonucleicAcids and Correlation with Cardiac Biomarkers in Acute Coronary Syndrome: A Comprehensive Systematic Review.

Acute coronary syndrome (ACS) is an acute and severe manifestation of coronary artery disease (CAD); thus, timely diagnosis can save a life. Commonly, cardiac troponin T (CTnT), cardiac troponin I (CTnI) or creatine kinase muscle/brain subtype (CK-MB) have been used as cardiac biomarkers to assess ACS with certain limitations, such as increased time to rise for diagnosis and increased levels in the patients with chronic kidney disease (CKD). Recently, micro-ribonucleic acids (miRNAs) have become potential candidates as biomarkers for cardiac ischemia due to their remarkable stability and reproducibility. Certain miRNAs, for instance, miR-1, miR-133a/b, miR-208a/b, and miR-499a, strongly increase in the serum or plasma of patients with acute cardiac ischemia, making them as cardio-specific miRNAs and prospective biomarkers in ACS. This literature review gives enlightenment about the regulation of cardio-specific miRNA in acute myocardial ischemia (AMI) and correlation with common cardiac biomarkers and time at which they increase in the blood.

P6437Growth differentiation factor-15 and stromal cell-derived factor-1 as long-term prognosis biomarkers in acute coronary syndrome

Abstract Introduction After an acute coronary syn bdrome (ACS) patients are at high risk of cardiovascular morbidity and mortality. In this scenario, Growth differentiation factor-15 (GDF-15) and Stromal cell derived factor-1 (SDF-1) has been reported as potential biomarkers in ACS. However, there is limited data about their combined use in long-term prognosis. Purpose To study the long-term prognostic value of GDF-15 and SDF-1 in ACS. Methods We included patients with ACS who underwent coronary angiography. During angiography an arterial blood sample was collected. Plasma SDF-1 and GDF-15 were measured and clinical data and long-term events were obtained. The cut-off point of SDF-1 and GDF-15 was identified individually by receiver operating characteristic curves. Patients were classified into 3 groups: 1) both biomarkers below cut-off points; 2) only one biomarker above cut-off points; 3) both biomarkers above cut-off points. Results A total of 238 patients were included. The median (IQR) age was 64 (55–74) year and 27.3% were female. Of all patients, 60.9% were admitted with non-ST-elevation myocardial infarction, 22.7% with ST-elevation myocardial infarction and 16.4% with unstable angina. The cut-off point of SDF-1 was 3283.5pg/mL and GDF-15 was 1849ng/L. A total of 127 patients were in group 1, 64 in group 2 and 47 in group 3. Group 3 patients were associated with older age, hypertension, dyslipidemia, diabetes mellitus and history of myocardial infarction (MI), stroke, chronic kidney disease and peripheral artery disease. Besides, they were more likely to have left ventricular dysfunction (ejection fraction &lt;40%) and significant three vessels stenosis. During 6.5 years of follow-up 8 patients died (6.3%) in group 1, 7 patients died (10.9%) in group 2 and 25 patients died (53.2%) in group 3 (Figure 1). Multivariate Cox analysis showed that high levels of SDF-1 and GDF-15 (group 3) were an independent predictor of all-cause death (HR 5.8; 95% CI 2.4 - 14.1; p&lt;0.001) and the composite of major adverse cardiovascular events (MACE) which were identified as all-cause death, nonfatal MI and heart failure (HR 3.9; 95% CI 2.1 - 7.3; p&lt;0.001). During follow-up 1 patient had heart failure in group 1 (0.8%), 3 patients (4.7%) in group 2 and 9 patients (19.1%) in group 3. Despite the low number of events of heart failure, the multivariate competing risks regression showed association between group 3 and heart failure during follow-up (HR 28.0; 95% CI 3.5 - 225.2; p=0.002). Higher levels of SDF-1 and GDF-15 (group 3) were not associated with new MI in multivariate competing risks regression. Regarding group 2, all multivariate analyses were non-significant. Cumulative survival and incidence curves Conclusions Higher values of combined GDF-15 and SDF-1 are an excellent predictor of all-cause death, MACE and heart failure in long-term follow-up of patients with ACS. The combined use of SDF-1 and GDF-15 may be useful in long-term ACS prognosis.

P3825Long-term prognostic value of growth differentiation factor-15 in acute coronary syndrome

Abstract Introduction Biomarkers plays a critical role in diagnostic, prognostication, and decision-making in cardiovascular medicine. Growth differentiation factor-15 (GDF-15) has been reported as a potential biomarker in acute coronary syndrome (ACS). However, there is limited data on the long-term prognostic value after an ACS. Purpose To study the long-term prognostic value of GDF-15 in ACS. Methods We included patients with ACS who underwent coronary angiography. During angiography an arterial blood sample was collected. Plasma GDF-15 were measured and clinical data and long-term events were obtained. As previously reported, risk categories were defined as low risk (&lt;1200ng/L), intermediate (1200–1800ng/L) and high risk (&gt;1800ng/L). Incremental prognostic value of GDF-15 for all-cause death was assessed on top of a clinical model (GRACE score, LVEF&lt;40% and age). Results A total of 358 patients were included; 157 as a low risk, 85 as an intermediate and 116 as a high risk. The median (IQR) age was 65 (56–74) years and 27.4% were female. Of all patients, 61.5% were admitted with non-ST-elevation myocardial infarction, 24.0% with ST-elevation myocardial infarction and 14.5% with unstable angina. Higher values of GDF-15 were consistently associated with an increased prevalence of cardiovascular risk factors. During 6 years of follow-up 54 patients died. Of those patients, 7 (4.5%) had values of GDF-15 below 1200ng/L, 6 (7.1%) between 1200–1800ng/L and 41 (35.3%) above 1800ng/L. After adjustment for a multivariate Cox regression model, GDF-15 &gt;1800ng/L were independently associated with all-cause death (HR 4.5; 95% CI 1.8–11.6; p=0.002) and the composite of major adverse cardiovascular events (MACE) which were identified as all-cause death, nonfatal MI and heart failure (HR 2.5; 95% CI 1.4–4.4; p=0.001). For long-term all-cause death a significant increase of the c-statistic was seen after addition of GDF-15 to the clinical model 0.871 (95% CI 0.817–0.924; p=0.019) as well as net reclassification improvement (0.769; 95% CI 0.487–1.051; p&lt;0.001) and integrated discrimination improvement (0.117; 95% CI 0.062–0.172; p&lt;0.001). Of 18 events of heart failure, 17 occurred in patients with GDF&gt;1800ng/L. A multivariate competing risk model showed a significant association between GDF-15&gt;1800ng/L and incidence of heart failure (adjusted HR 30.8; 95% CI 4.1–231.5; p=0.001) but non-significant association were found for myocardial infarction. KM figures and all-cause death ROC curve Conclusions In the setting of ACS GDF-15 can predict long-term all-cause death, MACE and heart failure and provides incremental prognostic value beyond traditional risks factors in the long-term all-cause death.

The Role of Insulin-Like Growth Factor-1 and Pregnancy-Associated Plasma Protein-A in Diagnosis of Acute Coronary Syndrome and Its Related Morbidities.

Introduction:Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that plays a role in atherosclerotic plaque destabilization. In recent studies, insulin-like growth factor-1 (IGF-1) has been introduced as a mediator of atherosclerosis. PAPP-A and IGF-1 level may be important diagnostic indicators of acute coronary syndrome (ACS).Objective:The present study tried to assess the diagnostic role of IGF-1 and PAPP-A biomarkers in ACS spectrum.Methods:The serum level of IGF-1, PAPP-A and troponin I was determined in 121 consecutive patients with ACS. Relationships were assessed by t-test, ANOVA and the non-parametric equivalent. Accuracy of biomarkers was measured by the area under the ROC curve (AUC) and optimal cut-off points to diagnose STEMI and NSTEMI using Youden index.Results:In patients with acute ST segment elevation myocardial infarction (STEMI), all of these three biomarkers were significantly higher than those in patients with unstable angina (P= 0.028 for IGF-1, P<0.001 for PAPP-A and Troponin-I). Mean level of IGF-1 in patients with renal failure was significantly higher than that in patients without renal failure (137.9±35.1 vs 105.1±46.9, P=0.003), but PAPP-A and serum Troponin-I level had no significant difference in renal failure groups (P>0.05). ROC curve analysis showed that after Troponin-I, PAPP-A was a good discriminator between patients with STEMI and patients with unstable angina (AUC=0.79). Optimum cut-off value for PAPP-A was found to be 89.2 ng/ml, with sensitivity and specificity of 66.7% and 83.8%, respectively.Conclusion:PAPP-A can be a novel biomarker for both identification of patients with STEMI and risk stratification in patients with ACS.

Association of Serum miR-186-5p With the Prognosis of Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention.

Circulating miR-186-5p is an emerging biomarker for acute coronary syndrome (ACS) patients. However, its kinetic signatures and prognostic values in ACS patients undergoing percutaneous coronary intervention (PCI) remain unclear. Levels of serum miR-186-5p were determined in 96 healthy controls and 92 ACS patients before and after PCI by qRT-PCR, and the physiologic state of miR-186-5p was analyzed by comparing its absolute concentrations in isolated exosomes and exosome-depleted supernatants. An average of 1 year of follow-up for ACS patients after PCI was performed. MiR-186-5p levels in the myocardium and serum of rats following left anterior descending coronary artery (LAD) ligation were measured. Serum miR-186-5p levels were found to be significantly increased in ACS patients upon admission compared with those of controls, but these high miR-186-5p levels gradually decreased within 1 week after PCI. Serum miR-186-5p was mainly present in an exosome-free form rather than membrane-bound exosomes. Within 1 year of follow-up, ACS patients with higher miR-186-5p levels upon admission exhibited a higher incidence of MACE after PCI. Different statistical analyzes further validated the independent prognostic values of serum miR-186-5p in ACS patients after PCI. Serum miR-186-5p levels in rats following LAD ligation were increased, and there was a decrease in myocardial miR-186-5p levels. Kyoto encyclopedia of genes and genomes (KEGG) analysis was performed to predict the related pathways of target genes of miR-186-5p, which suggested that miR-186-5p might be involved in ACS by regulating the inflammatory status and D-glucose metabolism. In conclusion, a distinctive expression signature of serum miR-186-5p may contribute to monitoring the clinical condition and assessing the prognosis of ACS patients undergoing PCI.

Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syndrome: A substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial.

We investigated the dynamics, associations with patient characteristics, other biomarkers, and clinical outcomes of pentraxin 3 in acute coronary syndrome. In multivariate analyses, pentraxin 3 measured in 5154 patients randomised in the Platelet Inhibition and Patients Outcomes (PLATO) trial (NCT00391872) was compared with leukocytes, high-sensitivity C-reactive protein, interleukin-6, cystatin C, N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15 concerning prediction of clinical outcome. Pentraxin 3 peaked earlier than high-sensitivity C-reactive protein and was more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein. The frequency of cardiovascular death, spontaneous myocardial infarction or stroke by quartiles of pentraxin 3 at admission was 6.1%, 7.3%, 9.7% and 10.7%, respectively (p<0.0001). The hazard ratio per 50% increase of pentraxin 3 was 1.13 (95% confidence interval: 1.07-1.19), p<0.0001. This association remained significant after stepwise adjustments for leukocytes/high-sensitivity C-reactive protein (1.09 (1.02-1.15)), p=0.009, interleukin-6 (1.07 (1.01-1.14)), p=0.026, and cystatin C (1.07 (1.00-1.13)), p=0.044, but not after adjustment for N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15. Admission pentraxin 3 was also associated with several of the individual endpoint components (cardiovascular death/spontaneous myocardial infarction; p=0.008, cardiovascular death; p=0.026, and spontaneous myocardial infarction; p=0.017), but not with stroke. Pentraxin 3 measured in the chronic phase (i.e. at one month) was still predictive of the composite endpoint in univariate analysis (1.12 (1.04-1.20) per 50% increase) p=0.0024, but not after adjustment for the other biomarkers. Admission level of pentraxin 3 is a modestly stronger predictor than high-sensitivity C-reactive protein and interleukin-6, but not than N-terminal prohormone brain natriuretic peptide or high-sensitivity troponin T, concerning cardiovascular outcome in acute coronary syndrome. Pentraxin 3 is more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein.

Low Protein Z Level: A Thrombophilic Risk Biomarker for Acute Coronary Syndrome

Low Protein Z Level: A Thrombophilic Risk Biomarker for Acute Coronary Syndrome

The Predictive Value of Potential Hematological Biomarkers in Acute Coronary Syndrome.

To explore the predictive value of potential hematological biomarkers in acute coronary syndrome (ACS). A total of 309 patients suffering ACS from June 2014 to June 2016 in The First Affiliated Hospital of Anhui Medical University were enrolled. The clinical data was studied retrospectively. All patients were divided into 3 groups based on the presence of elevated ST-segment including UA (150), STEMI (159), and NSTEMI (100). The association between potential hematological biomarkers of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell count (WBC), monocyte percentage (MO), and platelet width (PLW) and outcome of ACS including cTnI, occlusion of coronary artery, emergent PCI, and 30-day mortality was performed. Mean ± standard deviation was used to describe quantitative data of normal distribution. Inter-group comparison was performed by t or chi-square test and non-parametric test. M (P25, P75) was used to describe quantitative data of skewed distribution. Non-parametric tests revealed, except for PLW, there was significance between NLR, PLR, MO, and WBC and emergent PCI as well as 30-day mortality (p < 0.05). Multivariate logistic regression revealed that NLR was the best predictive factor of 30-day mortality. Meanwhile, it was found that the association between NLR, PLR, WBC, and cTnI was significant (p < 0.05). NLR is a useful and available factor in predicting outcome of ACS and more significant when combined with PLR, MO, and WBC.

Associations between circulating IgG antibodies to Apolipoprotein B100-derived peptide antigens and acute coronary syndrome in a Chinese Han population.

Objectives: Acute coronary syndrome (ACS) is the major cause of mortality worldwide and caused mainly by atherosclerosis of coronary arteries. Apolipoprotein B100 (ApoB100) is a major component of low-density lipoprotein (LDL) and its oxidation can trigger inflammation in vascular endothelial cells leading to atherosclerosis. The association between antibodies to ApoB100-derived antigens and atherosclerotic diseases has been studied in recent years, but the findings appear to be controversial. The present study developed an ELISA in-house with ApoB100-derived peptide antigens to circulating anti-ApoB100 IgG antibodies in patients with ACS. Methods: Fifteen ApoB100-derived peptide antigens (Ag1–Ag15) were designed to develop an in-house ELISA for the detection of circulating anti-ApoB100 IgG levels in 350 patients with ACS and 201 control subjects amongst a Chinese population. Binary logistic regression was applied to examine the differences in anti-ApoB IgG levels between the patient group and the control group with adjustment for a number of confounding factors; the correlation between anti-ApoB100 IgG levels and clinical characteristics was also tested. Results: Patients with ACS had significantly higher levels of plasma IgG for Ag1 (adjusted P<0.001) and Ag10 antigens (adjusted P<0.001). There was no significant increase in the levels of IgG to the other 13 antigens in these ACS patients. In the control group, anti-Ag10 IgG levels were positively correlated with age, high-density lipoprotein (HDL), and ApoA levels (P≤0.001 for all) and negatively correlated with blood triglyceride (TG) (P=0.008); in the patient group, anti-Ag10 IgG levels were positively correlated with LDL (P=0.003), and negatively correlated with ApoA (P=0.048) and systolic blood pressure (SBP) (P=0.036). The area under ROC (receiver operator characteristic) curve (AUC) was 0.612 (95% confidence interval (CI): 0.560–0.664; P<0.001) in anti-Ag1 IgG assay and 0.621 (95% CI: 0.569–0.672; P<0.001) in anti-Ag10 IgG assay. Conclusion: Circulating IgG for ApoB100-derived peptide antigens may be a useful biomarker of ACS, although anti-ApoB IgG levels were not associated with the coronary artery plaque burden characterized by the coronary Gensini score.

Urinary metabonomic study of patients with acute coronary syndrome using UPLC-QTOF/MS

This urinary metabonomic study aimed to identify the potential metabolic biomarkers in acute coronary syndrome (ACS) patients. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to analyze the urine samples from ACS patients and healthy controls. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to characterizing the endogenous metabolites and potential biomarker, respectively. Among twenty biomarkers that functioned in nine metabolic pathways, nine biomarkers were found up-regulated significantly, including of isobutyryl‑l‑carnitine, 3‑methylglutarylcarnitine, cinnavalininate, l‑tryptophan, 3‑methyldioxyindole, palmitic acid, N4‑acetylaminobutanal, 3‑sulfino‑l‑alanine and S‑adenosyl‑l‑homocysteine. The other eleven biomarkers were showed down-regulated, including of l‑lactic acid, trigonelline, nicotinuric acid, l‑alanine, d‑alanyl‑d‑alanine, creatine, N4‑acetylaminobutanoate, glutathionyl spermidine, 5‑methoxytryptamine, kynurenic acid and xanthurenic acid. This study also implied that fatty acid metabolism, fatty acid β‑oxidation metabolism, amino acid metabolism and TCA cycle played important roles in ACS. Therefore, urinary metabolomics may improve the diagnosis efficacy of ACS and make it more accurate and comprehensive for ACS diagnosis.

Low Protein Z Level: A Thrombophilic Risk Biomarker for Acute Coronary Syndrome.

Acute coronary syndrome (ACS) encompasses a range of thrombotic coronary artery diseases. Protein Z (PZ)/PZ-dependent protease inhibitor complex is a natural anticoagulant system with a presumptive role for PZ deficiency in the pathogenesis of ACS. We aimed to evaluate plasma PZ level and role as a risk biomarker in Egyptian patients with ACS. Hundred patients with stable ACS and 60 matched controls were enrolled. ACS patients were divided into 3 clinical subgroups (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina), and 2 age subgroups (group A ≤ 55years, and group B > 55years). Plasma PZ levels were evaluated using enzyme linked immunosorbent assay. Lower PZ levels were found in ACS patients' group and clinical subgroups compared with controls. PZ levels showed a decrease with increasing age and were lower in females versus males. Lower PZ levels were found in hypertensive ACS patients in both age subgroups. Smokers and patients with family history of ACS in group A had lower PZ levels, while group B revealed lower PZ among diabetic patients. In group A, increased number of ACS conventional risk factors was associated with lower PZ levels. PZ level 3.7μg/mL was the best cut-off value for prediction of ACS. Logistic regression analyses approved PZ as an independent risk biomarker for ACS. PZ levels are reduced in stable ACS and are significantly and independently associated with increased susceptibility for ACS, denoting PZ deficiency as a reliable thrombophilic risk biomarker in Egyptian patients with ACS.

MIF mRNA Expression and Soluble Levels in Acute Coronary Syndrome.

Acute coronary syndrome (ACS) describes any condition characterized by myocardial ischaemia and reduction in blood flow. The physiopathological process of ACS is the atherosclerosis where MIF operates as a major regulator of inflammation. The aim of this study was to assess the mRNA expression of MIF gene and its serum levels in the clinical manifestations of ACS and unrelated individuals age- and sex-matched with patients as the control group (CG). All samples were run using the conditions indicated in TaqMan Gene Expression Assay protocol. Determination of MIF serum levels were performed by enzyme-linked immunosorbent assay and MIF ELISA Kit. ST-segment elevation myocardial infraction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) showed 0.8 and 0.88, respectively, less expression of MIF mRNA with regard to CG. UA and STEMI presented more expression than NSTEMI 5.23 and 0.68, respectively. Otherwise, ACS patients showed significant higher MIF serum levels (p=0.02) compared with CG. Furthermore, the highest soluble levels of MIF were presented by STEMI (11.21 ng/dL), followed by UA (10.34 ng/dL) and finally NSTEMI patients (8.75 ng/dL); however, the differences were not significant. These novel observations further establish the process of MIF release after cardiovascular events and could support the idea of MIF as a new cardiac biomarker in ACS.

Measurement of plasma choline in acute coronary syndrome: importance of suitable sampling conditions for this assay

Blood choline has been proposed as a predictor of acute coronary syndrome (ACS), however different testing procedures might affect the choline concentration because the lysophospholipase D activity of autotaxin (ATX) can convert lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline in human blood. Although the influences of ATX on LPA levels are well known in vivo and in vitro, those on choline have not been elucidated. Therefore, we established suitable sampling conditions and evaluated the usefulness of plasma choline concentrations as a biomarker for ACS. Serum LPA and choline concentrations dramatically increased after incubation depending on the presence of ATX, while their concentrations in plasma under several conditions were differently modulated. Plasma choline levels in genetically modified mice and healthy human subjects, however, were not influenced by the ATX level in vivo, while the plasma LPA concentrations were associated with ATX. With strict sample preparation, the plasma choline levels did not increase, but actually decreased in ACS patients. Our study revealed that ATX increased the choline concentrations after blood sampling but was not correlated with the choline concentrations in vivo; therefore, strict sample preparation will be necessary to investigate the possible use of choline as a biomarker.

Diagnostic and prognostic micro-RNAs in ischaemic stroke due to carotid artery stenosis and in acute coronary syndrome: a four-year prospective study.

Circulating microRNAs (miRs) levels are potentially important diagnostic and prognostic biomarkers in acute coronary syndrome (ACS) or cerebral ischaemic events (CIE) resulting from internal carotid artery stenosis (ICAS). This four-year prospective study aimed to compare the levels of circulating miRs in ACS vs. CIE patients, and investigate miRs potentially associated with risk of recurrent cardiovascular events. The circulating miRs levels (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375, and miR-499-5p) were compared in 43 (34 men, 57.6 ± 10.1 years) patients with ACS, and in 71 (47 men, 69.5 ± 9.6 years) with CIE due to ICAS. A four-year prospective evaluation of miRs associated with risk of cardiovascular death (CVD), myocardial infarction (MI), CIE, or all (CVD/MI/CIE) was performed. In ACS vs. CIE patients, the levels of miR-124-3p (p < 0.001), miR-134-5p (p = 0.012), miR-208b-3p (p < 0.001), miR-34a-5p (p < 0.001), and miR-499-5p (p < 0.001) were higher, while levels of miR-16-5p (p < 0.001) and miR-122-5p (p < 0.001) were lower. Levels of miR-1-3p (p = 0.195), miR-133a-3p (p = 0.333), miR-133b (p = 0.056), and miR-375 (p = 0.055) were non-statistically different. During follow-up (median 57 months, Q1-Q3: 54-60), CVD/MI/CIE occurred in 23 subjects, including eight CVDs, five non-fatal CIEs, and 10 non-fatal MIs. The multivariate Cox proportional hazard analysis (relative risk [RR]; 95% confidence interval [CI]) revealed that miR-208b-3p (1.225; 1.092-1.375), miR-34a-5p (0.963; 0.935-0.992), and miR-499-5p (0.077; 0.025-0.239) were independently associated with risk of CVD/MI/CIE, as well as risk of each event. Furthermore, miR-133b (1.009; 1.003-1.015) was associated with risk of CVD. This study shows that although most investigated miRs levels differ significantly between patients with ACS and CIE, similar levels of circulating miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we identified several common miRs as possible risk factors for recurrent cardiovascular events.