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Copeptin, a neuropeptide of unknown pathophysiological function that is stoichiometrically secreted with the antidiuretic hormone, is a non-specific marker of endogenous stress which has recently gained interest for its use within a dual-marker strategy in combination with cardiac troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI) in emergency department patients with suspected MI. Based on methodologically strong and consistent evidence from large diagnostic studies and even one randomized intervention study, current European Society of Cardiology Guidelines recommend copeptin and the dual-marker strategy for the early rule-out of MI when high-sensitivity cardiac troponin (hs-cTn) assays are not available. When used with conventional cTn assays, the incremental value of copeptin is large. When used with hs-cTn, the incremental value is very small and does not justify routine clinical use. This review aims to describe the structure, function, and release mechanism of copeptin; as well as to provide an explanation on why this biomarker should be used in the rule-out, and not in the rule-in, of NSTEMI., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: Cardiac and renal functions are major independent predictors of outcomes in both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). As B-type natriuretic peptide (BNP) seems to be a major mediator in the cross-talk between heart and kidneys, we aimed at evaluating its capacity to reflect cardiac and renal function in patients with STEMI and NSTEMI., Methods: We measured BNP plasma levels at hospital admission in 619 patients with STEMI (n = 346) and NSTEMI (n = 273), grouped according to left ventricular ejection fraction (LVEF; > or ≤40%) and estimated glomerular filtration rate (eGFR; > or ≤ 60 ml/min/1.73 m)., Results: Median BNP values were 82 (38-186), 121 (40-342), 219 (80-685), and 474 (124-1263) pg/ml in patients with normal LVEF and eGFR (n = 347), with LVEF 40% or less and eGFR higher than 60 ml/min/1.73 m (n = 120), with LVEF higher than 40% and eGFR 60 ml/min/1.73 m or less (n = 86), and with combined LVEF and eGFR reductions (n = 66), respectively (P < 0.0001). At general linear model, both LVEF higher than 40% (P < 0.0001) and eGFR 60 ml/min/1.73 m or less (P < 0.0001) independently predicted BNP values. At multivariable analysis, BNP, LVEF 40% or less, and eGFR 60 ml/min/1.73 m or less were found to be independent predictors of the combined end point of in-hospital death, cardiogenic shock, need for renal replacement therapy, or mechanical ventilation (P = 0.003; P < 0.0001; P = 0.01, respectively)., Conclusion: BNP plasma levels are closely related to LVEF and eGFR at hospital admission, in both STEMI and NSTEMI patients. Future studies should investigate whether BNP levels can summarize in a single parameter the prognostic information provided separately by cardiac and renal dysfunction.

Background: Recent 2015 ESC recommendations for the management of patients with suspected acute myocardial infarction (AMI) support that a single value of high-sensitivity cardiac troponin (HS-cTn) measured at presentation could rule out AMI if below the limit of blank (LoB) or detection (LoD)., Objectives: We aimed to evaluate whether an undetectable HS-cTnT at presentation safely rules out NSTEMI in unselected patients with chest pain., Patients and Methods: This is a post hoc analysis of two prospective cohorts with similar design that included patients suspected of AMI at three French university hospitals. Patients were followed-up during one month, before the adjudication of a final diagnosis., Results: 413 patients (mean age 58±17years) were analyzed; 45 (11%) had a final diagnosis of NSTEMI, and 26 (6%) had STEMI. The sensitivity of HS-cTnT value at 3ng/L (LoB) for NSTEMI was 97.8% [95% CI: 86.8-99.9], yielding a negative predictive value (NPV) of 99.3% [95% CI: 95.4-100.0]. Proportion of patients ruled out for NSTEMI was 32% when applying the LoB. The sensitivity of HS-cTnT value at 5ng/L (LoD) was 97.8% [95% CI: 86.8-99.9] yielding a NPV of 99.5% [95% CI: 96.5-100.0]. Proportion of patients ruled out for NSTEMI was 43% when applying the LoD. One patient (delay between onset of chest pain and presentation <3h) had NSTEMI and HS-cTnT

Background: A sizeable gap exists between guideline recommendations for treatment of acute coronary syndrome (ACS) and application of these recommendations in clinical practice. The CCC-ACS project is a novel national quality enhancement registry designed to help medical care providers bridge this gap, thereby improving clinical outcomes for ACS patients in China., Methods and Results: The CCC-ACS project uses data collection, analysis, feedback, rapid-cycle improvement, and performance recognition to extend the use of evidence-based guidelines throughout the health care system and improve cardiovascular health. The project was launched in 2014, with 150 centers recruited representing the diversity of care for ACS patients in tertiary hospitals across China. Clinical information for patients with ACS is collected via a Web-based data collecting platform, including patients' demographics, medical history, symptoms on arrival, in-hospital treatment and procedures, in-hospital outcomes, and discharge medications for secondary prevention. Improvement in adherence to guideline recommendations is facilitated through monthly benchmarked hospital quality reports, recognition of hospital quality achievement, and regular webinars. As of April 16, 2016, a total of 35,616 ACS cases have been enrolled., Conclusions: The CCC-ACS is a national hospital-based quality improvement program, aiming to increase adherence to ACS guidelines in China and improve patient outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The plateletcrit has been investigated as a new predictor of cardiovascular risk. The objective of our study was to investigate the role of admission plateletcrit in predicting long-term cardiovascular mortality in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI). We enrolled 296 patients with NSTEMI (mean age 59.2 ± 11.8 years; 228 men, 68 women) in this study. The study population was divided into tertiles on the basis of admission plateletcrit values. A high plateletcrit (n = 98) was defined as a value in the upper third tertile (plateletcrit >0.23), and a low plateletcrit (n = 198) was defined as any value in the lower two tertiles (plateletcrit ≤0.23). The median follow-up time was 38 months. In multivariate analyses, a significant association was noted between high plateletcrit values and the adjusted risk of long-term mortality (odds ratio = 12.15, 95% confidence interval = 1.78-82.77; P < 0.001). In the Kaplan-Meier survival analysis, the long-term mortality rate was 20.4% in the high plateletcrit group versus 4.5% in the low plateletcrit group (P < 0.001). Long-term major advanced cardiac events (MACE), hospitalization for heart failure and reinfarction were significantly higher in patients with high plateletcrit. Admission plateletcrit is a strong and independent predictor of long-term cardiovascular mortality in patients with NSTEMI.

Aims: In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was started as early as possible for patients with suspected acute coronary syndrome by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism Cohort substudy, reported here, we investigated potential modes of GIK action on specific circulating metabolic components. Specific attention was given to suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been posed as part of the early GIK action related to averting cardiac arrest., Methods: We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and the homeostasis model assessment (HOMA) index., Results: With GIK, there was rapid suppression of FFA levels with estimated levels for GIK and placebo groups after 2 hours of treatment of 480 and 781 μmol/L (P<.0001), even while patterns of FFA saturation remained unchanged. There were no significant changes in the HOMA index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P = .07), suggesting that GIK infusions were not countered by insulin resistance. Also, neither placebo nor GIK altered endogenous insulin secretion as reflected by unchanging C-peptide levels., Conclusion: These mechanistic observations support the potential role of FFA suppression in very early cardioprotection by GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with respect to its insulin and glucose composition, as it induced no endogenous insulin secretion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: We evaluated cellular origin, numbers, and procoagulant activity of phosphatidylserine-positive microparticles (MPs) among subgroups in acute coronary syndromes (ACS)., Materials and Methods: Parameters were measured on admission, days 1 (within 24 h of admission), 2, 3, and 7. All ST-elevated myocardial infarction (STEMI) patients presented more than 3 h from symptom onset and received fibrinolysis treatment; controls included unstable angina and non-STEMI patients as well as healthy controls. Phosphatidylserine-positive MPs were detected by flow cytometry, whereas procoagulant activity was assessed by coagulation time, purified coagulation complex assays, and fibrin formation. MP-induced fibrins were visualized by confocal microscopy., Results: On admission, the total MP count was ∼2.5-fold higher in the ACS groups compared with the healthy controls (P<0.05), primarily originating from platelets and endothelial cells, and there were no significant differences among ACS subgroups. Specifically, leukocyte-derived and erythrocyte-derived MPs were higher in the STEMI group compared with unstable angina and non-STEMI groups (both P<0.05). Further, MPs from the ACS groups reduced coagulation time by 27.5% and induced intrinsic and extrinsic FXase, prothrombinase, and fibrin formation by 2.8-, 2.3-, 2.5-, and 1.7-fold, respectively (P<0.05 for all), whereas blocking phosphatidylserine with lactadherin inhibited ∼70% of procoagulant activity. MP number and concomitant coagulation decreased significantly by day 2 and continued to decrease gradually during the recovery period., Conclusion: This study shows that MP characteristics from circulating blood may be used as prognostic indicators to reflect the origin cell of activation and thrombophilic states found in ACS subgroups.

It is unclear whether changes in mean platelet volume (MPV) are associated with total mortality in acute coronary syndromes. We investigated whether the change in MPV predicts total mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We retrospectively analyzed 419 consecutive patients (19 patients were excluded). The remaining patients were categorized as survivors (n = 351) or nonsurvivors (n = 49). Measurements of MPV were performed at admission and after 24 hours. The difference between the 2 measurements was considered as the MPV change (ΔMPV). The end point of the study was total mortality at 1-year follow-up. During the follow-up, there were 49 deaths (12.2%). Admission MPV was comparable in the 2 groups. However, both MPV (9.6 ± 1.4 fL vs 9.2 ± 1.0 fL, P = .044) and ΔMPV (0.40 [0.10-0.70] fL vs 0.70 [0.40-1.20] fL, P < .001) at the first 24 hours were higher in nonsurvivors than survivors. In multivariate analysis, ΔMPV was an independent predictor of total mortality (odds ratio: 1.84, 95% confidence interval: 1.28-2.65, P = .001). An early increase in MPV after admission was independently associated with total mortality in patients with NSTEMI. Such patients may need more effective antiplatelet therapy., (© The Author(s) 2016.)

In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. © 2016 IUBMB Life, 68(8):673-682, 2016., (© 2016 International Union of Biochemistry and Molecular Biology.)

Background: Mean platelet volume (MPV) is a simple and reliable indicator of platelet size that correlates with platelet activation and their ability to aggregate. We studied the predictive value of MPV in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention (PCI)., Methods: We analyzed the consecutive records of 1001 patients who were hospitalized due to NSTEMI at our center. The primary end point was a composite end point that included the rates of all-cause death, non-fatal myocardial infarction, and acute coronary syndrome (ACS) driven revascularization at 12 months. The enrolled patients were stratified according to the quartile of the MPV level at admission., Results: Along with the increasing quartile of MPV, the 12-month composite end point increased significantly (p = 0.010), and this association remained significant after the risk-adjusted analyses (per 1 fL higher MPV; adjusted hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.02-1.27; p = 0.026). In the multivariate analysis, the MPV was also an independent factor of all-cause mortality (per 1 fL increase; adjusted HR 1.34; 95% CI 1.12-1.61; p = 0.0014) and death or non-fatal myocardial infarction (per 1 fL increase; adjusted HR 1.16; 95% CI 1.03-1.31; p = 0.017)., Conclusion: In patients with NSTEMI treated with PCI, a high MPV value was associated with a significantly increased incidence of long-term adverse events, particularly for all-cause mortality.

The influence of glucagon-like peptide-1 has been studied in several studies in patients with acute myocardial infarction, but not in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We planned to evaluate the effects of liraglutide on left ventricular function in patients with NSTEMI. A total of 90 patients were randomized 1:1 to receive either liraglutide (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days) or placebo for 7 days. Eighty-three patients completed the trial. Transthoracic echocardiography was used to assess left ventricular function. At 3 months, the primary endpoint, the difference in the change in left ventricular ejection fraction between the two groups was +4.7 % (liraglutide vs. placebo 95 % CI +0.7 to +9.2 % P = 0.009) under intention-to-treat analysis. The difference in decrease in serum glycosylated hemoglobin levels was -0.2 % (liraglutide vs. placebo 95 % CI -0.1 to -0.3 %; P < 0.001). Inflammation and oxidative stress improved significantly in the liraglutide group compared to the placebo group. Liraglutide could improve left ventricular function in patients with NSTEMI, making it a potential adjuvant therapy for NSTEMI.

Patients with non-ST segment elevation myocardial infarction (NSTEMI) are at high risk for atherothrombotic recurrences. Dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 receptor inhibitor clopidogrel significantly reduces the ischemic events in NSTEMI patients and has represented the mainstay of treatment for over a decade. However, a considerable number of patients continue to experience thrombotic complications, which may be in part due to inadequate platelet inhibition induced by this treatment regimen. This underscores the need for more potent antithrombotic treatment regimens for the long-term prevention of atherothrombotic events in NSTEMI patients. These include novel generation P2Y12 receptor blockers, such as prasugrel and ticagrelor, or adjunctive antiplatelet or anticoagulant therapies, such as vorapaxar [a protease-activated receptors (PAR)-1 receptor inhibitor] or rivaroxaban (a factor Xa inhibitor), respectively. Since ischemic events accrue over time in NSTEMI patients, prolonging intensified antiplatelet therapy beyond 1 year has also been investigated. However, although intensified and prolonged antithrombotic treatment regimens reduce ischemic events, this occurs at the expense of an increased risk of bleeding complications. This article encompasses the current state of the art on antithrombotic therapies for the secondary prevention of atherothrombotic events in patients with NSTEMI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Natriuretic peptides are diagnostic/prognostic biomarkers in major cardiovascular diseases. We aimed at assessing the predictive role of N-terminal pro-A-type (NT-proANP) and pro-B-type (NT-proBNP) natriuretic peptides levels toward cardiovascular outcome in both stable and unstable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in a non-primary PCI setting., Methods: A total of 395 patients undergoing PCI with stent implantation for either stable angina (SA) or non ST-elevation acute coronary syndrome (NSTE-ACS) were enrolled. Pre-procedural NT-proANP and NT-proBNP levels were measured. Occurrence of major adverse cardiac events (MACEs), composite of cardiac death, non-fatal myocardial infarction, and clinically driven target lesion revascularization (c-TLR), was the endpoint of the study. Follow up mean time was 48.53±14.69months., Results: MACEs occurred in forty-four patients (11%) during follow up. Both NT-proANP levels [3170 (2210-4630) vs 2283 (1314-3913) fmol/mL, p=0.004] and NT-proBNP levels [729 (356-1353) vs 511 (267-1006) fmol/mL, p=0.04] were significantly higher in patients with MACEs compared to patients without MACEs. Similar results were found when considering hard MACEs (myocardial infarction and cardiac death). NT-proANP levels were significantly higher in patients with c-TLR compared with patients without c-TLR [3705 (2766-5184) vs 2343 (1340-3960) fmol/mL, p=0.021]. At multivariate analysis, NT-proANP levels were a significant predictor of MACEs (HR 1.09, 95% CI 1.03-1.18, p=0.04). Kaplan-Meyer curves revealed that patients with elevated NT-proANP levels (>2.100fmol/mL) had a lower MACE free survival (p=0.003)., Conclusions: Both NT-proANP and NT-proBNP levels were higher in CAD patients experiencing MACEs following PCI in a non-primary setting. Notably, only NT-proANP levels significantly affected prognosis after PCI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Non-ST elevation myocardial infarction (NSTEMI) is one of the most common manifestations of acute coronary syndromes (ACS). We evaluated the prognostic role of cardiac troponin I (cTnI) at presentation and peak cardiac troponin I in patients with NSTEMI., Methods: We consecutively enrolled 215 subjects presenting with NSTEMI. Subjects were followed up for 1 year. cTnI at presentation and the peak value of cTnI were measured. The primary end point was defined as cardiovascular death, readmission to hospital with heart failure and new ACS., Results: The subjects who presented the primary end point (49 subjects) had significantly increased values of peak cTnI compared to subjects free of cardiovascular events [7.19 (2.97-21.32) vs. 4.09 (1.18-11.85) ng/l; p = 0.002]. Nevertheless, cTnI at presentation did not differ between subjects who presented the primary end point and those free of events (p = 0.39). Multivariate Cox regression analysis after adjustment for confounders revealed by the univariate analysis showed that for an increase in peak cTnI from 1 to 10 ng/l, there is a 60% anticipated increase in the relative risk to present the primary end point (p = 0.04)., Conclusion: These findings documented the different prognostic significance of cTnI at presentation and peak cTnI in patients presenting with NSTEMI, and highlighted the importance of monitoring the levels of cTnI in this high-risk population., (© 2016 S. Karger AG, Basel.)

Aim: To evaluate the usefulness of copeptin as a rapid and reliable marker for discarding non-ST elevation acute myocardial infarction (NSTEMI) in patients attended in an Emergency Care Department due to acute chest pain with a normal or non-diagnostic electrocardiogram and a negative first troponin I result., Design: A prospective observational study was carried out., Setting: The Emergency Care Department of a university hospital., Patients: The study comprised a total of 97 patients attended in the Emergency Care Department due to chest pain suggestive of acute coronary syndrome with an evolution of under 12h, a non-diagnostic electrocardiogram and a negative first troponin I result., Interventions: None., Variables of Interest: Patient demographic data and baseline characteristics, copeptin upon admission, troponin I upon admission and after 6h, and final diagnosis., Results: The final diagnosis was NSTEMI in 14 patients (14.4%) -no significant differences in copeptin concentration being observed between the 2 groups, though a tendency towards higher values was recorded in the NSTEMI group (median: 24.6pmol/l [interquartile range: 42.0] vs. 12.0pmol/l [16.1]; P=.06). The AUC ROC for copeptin upon admission was 0.657 (95%CI: 0.504-0.810), with a negative predictive value of 92% for a cutoff point of 14pmol/l., Conclusions: Copeptin determination upon admission to the Emergency Care Department in patients with chest pain for ≤12h, suggestive of acute coronary syndrome, with a non-diagnostic electrocardiogram and a negative first troponin I determination does not allow rapid and reliable exclusion of the presence of NSTEMI. Serial troponin I measurements are needed in this respect., (Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)