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Background: Acute coronary syndrome (ACS) is a type of coronary heart disease (CHD), which is responsible for one-third of total deaths in people older than 35 years. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis. Studies demonstrate that Ischaemia Modified Albumin (IMA) is more sensitive in diagnosing ischemic chest pain compared to cardiac troponin T and electrocardiogram, and its combination with these tests significantly increases the sensitivity for diagnosing unstable angina, non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI), with high positive and negative predictive values, making it a valuable tool for ruling out ACS in patients with inconclusive diagnoses in the emergency department., Methods: This prospective cohort study, conducted at the Teaching Hospital, Peradeniya, Sri Lanka, from 2015 to 2019, investigated ischemia-modified albumin (IMA) levels in 330 acute coronary syndrome (ACS) patients. Excluding those with various chronic conditions and those on specific medications, serum IMA was analyzed using a colorimetric assay based on cobalt (II) binding to human serum albumin affected by myocardial ischemia. Serum IMA levels were measured, and statistical analyses, including non-parametric tests and correlation analyses, were conducted to evaluate the association between IMA levels and various demographic and clinical factors., Results: IMA concentrations were found to be non-normally distributed, with an average concentration of 0.252 ± 0.123 AU. No overall significant gender-based difference in IMA levels was observed, though within the younger age group (< 59 years), males exhibited higher IMA concentrations than females. Significant gender differences were observed in the younger age group, with males showing higher IMA levels than females (p = 0.033). No significant differences in IMA levels were found across different ethnicities (p = 0.217) or BMI categories (p = 0.056). A significant increase in IMA levels was noted in ACS patients compared to control subjects (p < 0.001). Correlation analysis revealed significant associations between IMA levels and total cholesterol (r = 0.262, p = 0.009) and low-density lipoprotein (LDL) levels (r = 0.280, p = 0.006). Notably, a significant gender difference in IMA levels was found in obese patients, suggesting physiological differences in response to obesity. The study also revealed higher IMA concentrations in NSTEMI and STEMI patients compared to those with unstable angina., Conclusion: The study confirms elevated IMA levels in ACS patients, supporting its diagnostic potential. It reveals demographic influences, such as higher IMA levels in younger males and significant gender-specific differences in obese patients. Personalized approaches considering demographics and lipid management are essential for ACS risk reduction and IMA's role in management., (© 2024. The Author(s).)

Introduction: In this study, we aimed to investigate the effect of HbA1C/C-peptide ratio on short-term mortality (this period is defined as 30 days after diagnosis) in the patients with myocardial infarction. Materials & Methods: Around 3245 patients who were admitted due to ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction underwent primary percutaneous coronary intervention between October 2020 and 2024 were included in this study. Results: In the receiver operating characteristic analysis, the predictive power of the HCR score for mortality in ST-elevation myocardial infarction patients was determined to be 83% sensitivity and 81% specificity. In non-ST-elevation myocardial infarction, this was determined to be 78% sensitivity and 75% specificity. Conclusion: The HbA1C/C-peptide ratio score can predict poor clinical outcomes early, reducing mortality and morbidity in patients with myocardial infarction.

Background: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI)., Methods and results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis., Conclusions: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Background: Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need., Methods and Results: A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P =0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance., Conclusions: MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.

Objective: Myocardial infarction is associated with right ventricular (RV) remodeling. Glypican-6 (GPC6), a member of the membrane proteoglycan family, plays a significant role in cardiac remodeling. This study aims to determine if GPC6 can predict RV remodeling after percutaneous coronary intervention (PCI) in patients with non-ST segment elevation myocardial infarction (NSTEMI)., Methods: The study enrolled 164 consecutive patients with NSTEMI and controls. It compared baseline plasma GPC6 levels, echocardiography, and laboratory parameters between the RV remodeling and non-RV remodeling groups with NSTEMI. Echocardiographic data were measured at baseline and at six months., Results: GPC6 levels were higher in the NSTEMI group 11.06 ng/mL (4.61-18.17) vs. 5.98 ng/mL (3.81-9.83) compared to the control group in the initial phase. RV remodeling, defined as a ≥ 20% increase in RV end-diastolic area (RV EDA), was observed in 23 patients (30%). After six months, RV EDA increased significantly from baseline 18.68 ± 1.20 cm2 vs. 24.91 ± 1.08 cm2, P < 0.001. GPC6 was a significant independent predictor of RV remodeling (hazard ratio [HR]: 1.546, 95% confidence interval [CI]: 1.056-2.245, P < 0.001). Receiver operating characteristic curve (ROC) analyses showed that GPC6 values > 15.5 ng/mL (area under the curve [AUC] = 0.828, sensitivity: 70%, specificity: 74%, P < 0.001) were strong predictors of RV remodeling., Conclusion: NSTEMI patients should be closely monitored for RV remodeling. GPC6 appears useful in detecting RV remodeling following NSTEMI in patients undergoing PCI.

This study aims to investigate the mechanism of platelet activation-induced thrombosis in patients with acute non-ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy-associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un-offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy-associated proteins and the expression of autophagy-associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un-offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy-related protein expression decreased, and the expression of αIIbβ3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbβ3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Cardiovascular disease is the major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Novel markers of insulin resistance and progression of atherosclerosis include the triglycerides and glucose index (TyG index), the triglycerides and body mass index (Tyg-BMI) and the metabolic score for insulin resistance (METS-IR). Establishing independent risk factors for in-hospital death and major adverse cardiac and cerebrovascular events (MACCE) in patients with myocardial infarction (MI) remains critical. The aim of the study was to assess the risk of in-hospital death and MACCE within 12 months after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with and without T2DM based on TyG index, Tyg-BMI and METS-IR., Methods: Retrospective analysis included 1706 patients with STEMI and NSTEMI hospitalized between 2013 and 2021. We analyzed prognostic value of TyG index, Tyg-BMI and METS-IR for in-hospital death and MACCE as its components (death from any cause, MI, stroke, revascularization) within 12 months after STEMI or NSTEMI in patients with and without T2DM., Results: Of 1706 patients, 58 in-hospital deaths were reported (29 patients [4.3%] in the group with T2DM and 29 patients [2.8%] in the group without T2DM; p = 0.1). MACCE occurred in 18.9% of the total study population (25.8% in the group with T2DM and 14.4% in the group without T2DM; p < 0.001). TyG index, Tyg-BMI and METS-IR were significantly higher in the group of patients with T2DM compared to those without T2DM (p < 0.001). Long-term MACCE were more prevalent in patients with T2DM (p < 0.001). The area under the ROC curve (AUC-ROC) for the prediction of in-hospital death and the TyG index was 0.69 (p < 0.001). The ROC curve for predicting in-hospital death based on METS-IR was 0.682 (p < 0.001). The AUC-ROC values for MACCE prediction based on the TyG index and METS-IR were 0.582 (p < 0.001) and 0.57 (p < 0.001), respectively., Conclusions: TyG index was an independent risk factor for in-hospital death in patients with STEMI or NSTEMI. TyG index, TyG-BMI and METS-IR were not independent risk factors for MACCE at 12 month follow-up. TyG index and METS-IR have low predictive value in predicting MACCE within 12 months after STEMI and NSTEMI., (© 2024. The Author(s).)

Non-ST-segment elevation acute myocardial infarction (NSTEMI) is a life-threatening clinical emergency with a poor prognosis. However, there are no individualized nomogram models to identify patients at high risk of NSTEMI who may undergo death. The aim of this study was to develop a nomogram for in-hospital mortality in patients with NSTEMI to facilitate rapid risk stratification of patients. A total of 774 non-diabetic patients with NSTEMI were included in this study. Least Absolute Shrinkage and Selection Operator regression was used to initially screen potential predictors. Univariate and multivariate logistic regression (backward stepwise selection) analyses were performed to identify the optimal predictors for the prediction model. The corresponding nomogram was constructed based on those predictors. The receiver operating characteristic curve, GiViTI calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. The nomogram model consisting of six predictors: age (OR = 1.10; 95% CI: 1.05-1.15), blood urea nitrogen (OR = 1.06; 95% CI: 1.00-1.12), albumin (OR = 0.93; 95% CI: 0.87-1.00), triglyceride (OR = 1.41; 95% CI: 1.09-2.00), D-dimer (OR = 1.39; 95% CI: 1.06-1.80), and aspirin (OR = 0.16; 95% CI: 0.06-0.42). The nomogram had good discrimination (area under the curve (AUC) = 0.89, 95% CI: 0.84-0.94), calibration, and clinical usefulness. In this study, we developed a nomogram model to predict in-hospital mortality in patients with NSTEMI based on common clinical indicators. The proposed nomogram has good performance, allowing rapid risk stratification of patients with NSTEMI., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Elevated circulating D-dimer levels have been shown to be a predictor of in-hospital mortality in a variety of diseases; however, the relationship between D-dimer and the in-hospital prognosis of non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. This retrospective study included 662 non-diabetic patients with NSTEMI. Independent risk factors were identified by multivariate analyses, and the receiver operating characteristic (ROC) curve analyses were performed to compare the predictive value of D-dimer, albumin (ALB), and D-dimer to albumin ratio (DAR) for in-hospital death in NSTEMI. Logistic regression model with restricted cubic spline (RCS) was used to further explore the linear or nonlinear relationship between D-dimer and the risk of death. In-hospital mortality occurred in 38 (5.7%) patients. Multivariate analysis showed that D-dimer (per increase of 500 ng) was identified as an independent predictor for in-hospital mortality in non-diabetic patients with NSTEMI (OR = 1.19, 95% CI: 1.03-1.40, P  = 0.036). D-dimer demonstrated good predictive performance for in-hospital mortality with an area under the ROC curve (AUC) value of 0.75 (95% CI: 0.66-0.83), and there was no significant difference in the predictive ability of D-dimer, ALB (AUC = 0.70, 95% CI: 0.61-0.79) and DAR (AUC = 0.75, 95% CI: 0.66-0.84). In addition, RCS analysis showed a linear relationship between D-dimer and the risk of in-hospital mortality (P for nonlinear = 0.747). D-dimer can be used as a simple, reliable and valuable biomarker for predicting in-hospital mortality in non-diabetic patients with NSTEMI and is linearly associated with the risk of death.

Background: It has been demonstrated that glycated albumin (GA) is significantly associated with diabetes complications and mortality. However, among patients diagnosed with non-ST-elevation acute coronary syndrome (NSTE-ACS) administered percutaneous coronary intervention (PCI), the predictive value of GA for poor prognosis is unclear., Methods: This study eventually included 2247 NSTE-ACS patients in Beijing Anzhen Hospital, Capital Medical University in January-December 2015 who received PCI. All patients were followed up until death or for 48 months post-discharge. The primary endpoint was major adverse cardio-cerebral events (MACCEs), including all-cause death, non-fatal myocardial infarction, ischemia-induced revascularization and non-fatal ischemic stroke., Results: In total, 547 (24.3%) MACCEs were recorded during the follow-up period. Upon adjusting for potential confounders, GA remained an important risk predictor of MACCEs (As nominal variate: hazard ratio [HR] 1.527, 95% confidence interval [CI] 1.236-1.886, P < 0.001; As continuous variate: HR 1.053, 95% CI 1.027-1.079, P < 0.001). GA addition significantly enhanced the predictive ability of the traditional risk model (Harrell's C-index, GA vs. Baseline model, 0.694 vs. 0.684, comparison P = 0.002; continuous net reclassification improvement (continuous-NRI) 0.085, P = 0.053; integrated discrimination improvement (IDI) 0.007, P = 0.020)., Conclusion: GA is highly correlated with poor prognosis in NSTE-ACS patients undergoing PCI, suggesting that it may be a major predictive factor of adverse events among these individuals., (© 2022. The Author(s).)

Objective: Many recent studies have demonstrated that serum miRNA-208 (miR-208) could be a powerful biomarker in the early diagnosis of acute myocardial infarction (AMI). However, the result of previous studies was not accurate due to the small sample sizes and controversial issues. Therefore, this study was performed to investigate the relationship between the expression levels of miR-208 and AMI., Materials and Methods: According to the inclusion and exclusion criteria, a preliminary literature search was performed. The study was based on articles published in PubMed, Embase, Cochrane databases before September 30, 2019. Two staff members extracted data from the included articles for meta-analysis. These data were analyzed for sensitivity, specificity, diagnostic odds ratio, and summary receiver operator curve (SROC) analyses., Results: This study included 13 pieces of literature, which contains 1703 patients with AMI and 1589 controls. The main results of our meta-analysis were as follows: The pool sensitivity and specificity of miR-208 for diagnosing AMI was 83% and 97%. The area under the SROC curve (AUC) was 93%. Mir-208 had a highly effective diagnostic capacity to distinguish AMI from chest pain patients with an AUC of 93%., Conclusions: The results showed that circulating miR-208 was a reliable biomarker both for diagnosting ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). MiR-208 was sufficient to distinguish AMI patients with chest pain from healthy controls., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Rheumatoid factor (RF) has been associated with an increased likelihood of developing coronary artery disease and cardiovascular mortality. This study aimed to evaluate the relationship between serum RF levels and SYNTAX score I (SSI) in patients with acute myocardial infarction., Methods: This study included 418 consecutive patients who were diagnosed with acute myocardial infarction and underwent coronary angiography. The baseline serum RF levels of all patients were measured. The study population was divided into 2 groups, namely, ST-segment elevation myocardial infarction (STEMI) group (218 patients) and non-ST-segment elevation myocardial infarction (NSTEMI) group (200 patients). Each group was further divided into 2 subgroups, namely, SSI ≤22 group and SSI >22 group., Results: In the STEMI group, RF levels were significantly higher in the SSI >22 group than that in the SSI ≤22 group (13.0 IU/mL [7.0-51.0 IU/mL] versus 11.0 IU/mL [4.0-37.0 IU/mL], respectively, p=0.002). In the NSTEMI group, RF levels were significantly higher in the SSI >22 group than that in the SSI ≤22 group (15.5 IU/mL [8.0-69.5 IU/mL] versus 13.0 IU/mL [4.0-36.0 IU/mL, respectively], p<0.001). Forward conditional logistic regression analysis demonstrated that neutrophil-to-lymphocyte ratio, total cholesterol level, positive RF, and left ventricular ejection fraction were independently associated with intermediate and high SSI in patients with STEMI. Furthermore, cardiac troponin T levels and positive RF were independently associated with intermediate and high SSI in patients with NSTEMI., Conclusion: Serum RF concentrations are independently associated with SSI in patients with acute myocardial infarction.

Background: Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients., Methods: We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden's formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI., Results: There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74-2.76); GHR: OR 2.28 (95% CI 1.80-2.89); SHR: OR 2.20 (95% CI 1.73-2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01-1.90); HbA1c: OR 2.11 (95% CI 1.15-3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5-67.2; GHR 68.8% 95% CI 64.8-72.8; SHR: AUC 69.3%, 95% CI 65.4-73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7-76.3; GHR 71.9% 95% CI 67.7-76.2; SHR: AUC 71.7%, 95% CI 67.4-76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1-57.6; HbA1c: AUC 42.5%, 95% CI 37.6-47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1-70.0; HbA1c: AUC 51.1%, 95% CI 43.3-58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients., Conclusions: SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients., (© 2021. The Author(s).)

Objective: Beyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties., Methods: In a placebo-controlled trial, 117 patients with NSTEMI were randomised to a single dose of tocilizumab (n=58) or placebo (n=59) before coronary angiography. The NETs related markers double-stranded DNA (dsDNA), myloperoxidase-DNA (MPO-DNA) and citrullinated histone 3 (H3Cit) were measured at five consecutive time points during hospitalisation (days 1-3)., Results: Our major findings were: (1) H3Cit levels were significantly higher in the tocilizumab compared with the placebo group at all time points (all p<0.05), and H3Cit area under the curve (AUC) was 2.3 fold higher in the tocilizumab compared with placebo group (p<0.0001). (2) MPO-DNA and dsDNA did not differ between the groups. (3) In both treatment arms, dsDNA AUC was associated with TnT AUC. (4) Neutrophil count AUC correlated inversely to H3Cit AUC (p=0.015) in the total population., Conclusions: In patients with NSTEMI, treatment with tocilizumab is associated with increased circulating H3Cit levels, suggesting that tocilizumab enhances NETosis. Further studies should clarify whether NETosis is a relevant side effect of tocilizumab. Regardless of tocilizumab, dsDNA associated with TnT release, indicating a link between extracellular nuclear material and myocardial injury., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI., Methods: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained., Results: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001)., Conclusions: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.

Background: New-onset atrial fibrillation (NOAF) is common during acute myocardial infarction (AMI) and independently associated with worse prognosis. We aimed to validate the discrimination performance of CHA2DS2-VASc score combined with hs-CRP in the prediction of NOAF after AMI in elderly Chinese population., Methods: 311 consecutive elderly patients (age ≥ 65 years old) with AMI from 1 January 2018 to 1 January 2019 without atrial fibrillation history were enrolled in our study. Univariable and multivariable logistic regression analyses were used to identify risk factors of NOAF. The discrimination performance of different score models were evaluated using ROC curve analysis and AUCs were compared using the Z test., Results: 30 (9.65%) patients developed NOAF during hospitalization. The NOAF group were older and had higher hs-CRP, initial Killip class, BNP, LAD, CHADS2 score, CHA2DS2-VASc score, in-hospital mortality and lower LVEF and ACEI/ARB use (P < 0.05 vs group without NOAF for all measures). In multivariate regression analyses, age (OR = 1.127, 95% CI 1.063-1.196, P < 0.001) and hs-CRP (OR = 1.034, 95% CI 1.018-1.05, P < 0.001) were independent predictors of NOAF. In ROC curve analyses, both CHADS2 score (AUC = 0.624, 95% CI 0.516-0.733, P = 0.026) and CHA2DS2-VASc score (AUC = 0.687, 95% CI 0.584-0.79, P = 0.001) had acceptable but unsatisfactory discrimination performance in predicting NOAF after AMI. The combined model with CHA2DS2-VASc score and hs-CRP showed a significant better predictive value (AUC = 0.791, 95% CI 0.692-0.891, P < 0.001) compared to that of the CHA2DS2-VASc score alone (Z test, P = 0.008)., Conclusion: The combined model with CHA2DS2-VASc score and hs-CRP had high accuracy in predicting post-AMI NOAF.

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.

Vascular calcification contributes to the pathogenesis of coronary artery disease while matrix Gla protein (MGP) was recently identified as a potent inhibitor of vascular calcification. MGP fractions, such as dephosphorylated-uncarboxylated MGP (dp-ucMGP), lack post-translational modifications and are less efficient in vascular calcification inhibition. We sought to compare dp-ucMGP levels between patients with acute coronary syndrome (ACS), stratified by ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) status. Physical examination and clinical data, along with plasma dp-ucMGP levels, were obtained from 90 consecutive ACS patients. We observed that levels of dp-ucMGP were significantly higher in patients with NSTEMI compared to STEMI patients (1063.4 ± 518.6 vs. 742.7 ± 166.6 pmol/L, p < 0.001). NSTEMI status and positive family history of cardiovascular diseases were only independent predictors of the highest tertile of dp-ucMGP levels. Among those with NSTEMI, patients at a high risk of in-hospital mortality (adjudicated by GRACE score) had significantly higher levels of dp-ucMGP compared to non-high-risk patients (1417.8 ± 956.8 vs. 984.6 ± 335.0 pmol/L, p = 0.030). Altogether, our findings suggest that higher dp-ucMGP levels likely reflect higher calcification burden in ACS patients and might aid in the identification of NSTEMI patients at increased risk of in-hospital mortality. Furthermore, observed dp-ucMGP levels might reflect differences in atherosclerotic plaque pathobiology between patients with STEMI and NSTEMI.

Background and Aims: Liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are markers of hepatic dysfunction and fatty liver disease. Although ALT and AST have been suggested as risk factors for cardiovascular disease, their role as predictors of mortality after acute myocardial infarction (AMI) has not been established. The objective of this study was to investigate the predictive value of ALT and AST for mortality in patients with AMI., Methods: We analyzed records of 712 patients with AMI and no known liver disease treated at the Department of Cardiovascular Center in the First Hospital of Jilin University. The primary outcome was all-cause in-hospital mortality. Relationships between primary outcome and various risk factors, including serum transaminase levels, were assessed using multivariate logistic regression analysis., Results: Age (P < 0.001), hypertension (P = 0.034), prior myocardial infarction (P < 0.001), AST (P < 0.001), ALT (P < 0.001), creatinine (P = 0.007), blood urea nitrogen (P = 0.006), and troponin I (P < 0.001) differed significantly between ST-segment elevation myocardial infarction (STEMI) and non-STEMI. The following factors were associated with an increased risk of in-hospital all-cause mortality in patients with AMI: ALT ≥ 2ULN (adjusted odds ratio [AOR] 2.240 [95% confidence interval (CI), 1.331-3.771]; P = 0.002); age ≥ 65 year (AOR 4.320 [95% CI 2.687-6.947]; P < 0.001); increased fasting plasma glucose (FPG) (AOR 2.319 [95% CI 1.564-3.438]; P < 0.001); elevated D-dimer (AOR 2.117 [95% CI 1.407-3.184]; P < 0.001); elevated fibrinogen (AOR 1.601 [95% CI 1.077-2.380]; P = 0.20); and reduced estimated glomerular filtration rate (eGFR) (AOR 2.279 [95% CI 1.519-3.419]; P < 0.001)., Conclusions: Our findings demonstrated that elevated ALT was independently associated with increased in-hospital all-cause mortality in patients with AMI. Other risk factors were increased age, FPG, D-dimer, and fibrinogen and decreased eGFR.

Background: Under conditions of oxidative stress, hydroxyl radicals can oxidize phenylalanine (Phe) into various tyrosine (Tyr) isomers (meta-, ortho-, and para-tyrosine; m-, o-, and p-Tyr), depending on the location of the hydroxyl group on the oxidized benzyl ring. This study aimed to compare patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) and the serum levels of Phe and Tyr isomers at the aortic root and distal to the culprit lesion in both groups., Methods: Forty-four patients participated in the study: 23 with STEMI and 21 with NSTEMI. Arterial blood samples were taken from the aortic root through a guiding catheter and from the culprit vessel segment distal from the primary lesion with an aspiration catheter, during the percutaneous coronary intervention. Serum levels of Phe, p-Tyr, m-Tyr, and o-Tyr were determined using reverse-phase high-performance liquid chromatography., Results: Serum levels of Phe were significantly higher distal to the culprit lesion compared to the aortic root in patients with STEMI. Serum p-Tyr/Phe and m-Tyr/Phe concentration ratios were both lower distal to the culprit lesion than at the aortic root in patients with STEMI. There were no statistically significant differences with respect to changes in serum Phe and Tyr isomers distal to the culprit lesion compared to the aortic root in patients with NSTEMI., Conclusion: Our data suggest that changes in serum levels of different Tyr isomers can mediate the effects of oxidative stress during myocardial infarction., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Background: Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients., Methods: Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value., Results: Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks., Conclusions: In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients., (© American Association for Clinical Chemistry 2020.)

Background: We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain., Methods: Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used., Results: Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge., Conclusion: Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI., Prospero Registration: CRD42019154716., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. Approach and Results: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI., Conclusions: Sex-specific signaling in platelets seems to be a cross-species phenomenon. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.

Background Cardiac troponin (cTn) permits early rule-out/rule-in of patients admitted with possible non-ST-segment-elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule-out/rule-in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long-term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non-ST-segment-elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI (Abbott) (Abbott Diagnostics), and cTnI (sgx) (Singulex Clarity System) were measured in 971 admission and 465 1-hour samples. An admission and a 0/1 hour rule-out/rule-in algorithm were developed for the cTnI (sgx) assay and its diagnostic properties were compared with cTnT ESC (European Society of Cardiology), cTnI (Abbott)ESC , and 2 earlier cTnI (sgx) algorithms. The prognostic composite end point was all-cause mortality and future nonfatal myocardial infarction during a median follow-up of 723 days. non-ST-segment-elevation myocardial infarction prevalence was 13%. The novel cTnI (sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI (sgx)0/1 hour algorithm classified 92% of patients to rule-in or rule-out compared with ≤78% of comparators. Patients allocated to rule-out by the prior published 0/1 hour algorithms had significantly fewer long-term events compared with the rule-in and observation groups. The novel cTnI (sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule-out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non-ST-segment-elevation myocardial infarction but could rule-out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.

Introduction: Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI)., Methods: We conducted a retrospective case-control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR., Results: Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P < 0.001). After adjusting for age, gender, heart rate at admission, body mass index (BMI), and systolic blood pressure (SBP), blood group A was independently related to the increased risk of HR after AMI (OR = 2.781, 95% CI 1.174-7.198, P = 0.035), and remained as an independent risk factor of HR after AMI in different multivariate regression models., Conclusion: Blood group A is significantly associated with increased HR risk after AMI.

Objective: The expression of galectin-3 has been found to be increased in human atherosclerotic lesions, suggesting a role in atherogenesis. However, there is a lack of data regarding an association between galectin-3 and the extent, severity, and complexity of coronary artery disease (CAD). The aim of this study was to investigate the relationship between galectin-3 and SYNTAX Score I in patients with non-ST-segment elevation myocardial infarction (NSTEMI)., Methods: This study included a total of 95 consecutive patients who were diagnosed with NSTEMI and underwent coronary angiography. The baseline galectin-3 level of each patient was measured. The SYNTAX Score I of each patient was calculated using the online calculator (www.syntaxscore.com). The study population was divided into 2 groups: SYNTAX Score I ≤22 group (n=55) and SYNTAX Score I >22 group (n=40)., Results: The galectin-3 level was significantly higher in the SYNTAX Score I >22 group than in the SYNTAX Score I ≤22 group (22.1±8.3 ng/mL vs. 13.5±7.7 ng/mL; p<0.001). Forward stepwise logistic regression analysis demonstrated that galectin-3 (odds ratio [OR]: 1.195, 95% confidence interval [CI]: 1.097-1.302; p<0.001), left ventricular ejection fraction (OR: 0.941, 95% CI: 0.888-0.997; p=0.040), and platelet count (OR: 1.013, 95% CI: 1.003-1.024; p=0.014) were independently associated with intermediate and high SYNTAX scores. ROC analysis provided a cut-off value of 14.0 ng/mL for galectin-3 to predict an intermediate or high SYNTAX Score I with 75.0% sensitivity and 51.0% specificity (p<0.001)., Conclusion: In patients with NSTEMI, galectin-3 was associated with the extent, severity, and complexity of CAD as assessed by the SYNTAX Score I.

Background: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM., Methods: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint., Results: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients., Conclusions: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.

Background: Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity., Methods: In this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography., Results: From April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively)., Conclusion: In patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity., Competing Interests: The authors have declared that no competing interests exist.

Concentrations of different circulating microparticles (MPs) may have clinical and physiological relevance to cardiovascular disease pathologies., Purpose: To quantify plasma concentrations of CD31+/CD42b-, CD62E+, and CD34+ MPs across healthy individuals and those with coronary artery disease (CAD) or acute cardiovascular events (non-ST elevation myocardial infarction (NSTEMI)). Fasted blood was obtained from CAD patients (n = 10), NSTEMI patients (n = 13), and healthy older men (n = 15) 60-75 years old., Methods: CD31+/CD42b-, CD62E+, and CD34+ MPs were isolated from plasma and quantified using flow cytometry. Relationships between MP subtypes, fasting blood lipids, blood glucose, blood pressure, body mass index, and total number of medications were assessed., Results: Concentrations of CD31+/CD42b- MPs were significantly lower in CAD and NSTEMI subjects compared with healthy individuals (p = .02 and .003, respectively). No differences between groups were found for CD62E+ or CD34+ MPs (p > .05 for both). Surprisingly, among all variables assessed, only CD62E+ MP concentrations were positively correlated with triglyceride levels (p = .012) and inversely correlated with SBP (p = .03)., Conclusions: Our findings provide support for the use of different MP subtypes, specifically CD31+/CD42b- MPs, as a potential biomarker of cardiovascular disease. Importantly, results from this study should be looked at in adjunct to previous MP work in CVD conditions as a way of highlighting the complex interactions of variables such as comorbid conditions and medications on MP concentrations., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: The relationship between triglyceride-glucose index (TyG index) and the prevalence and prognosis of cardiovascular disease has been confirmed by former studies. However, it remains uncertain whether TyG index has a prognostic impact in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI)., Methods: The study retrospectively enrolled 798 patients (mean age: 60.9 ± 8.3 years; 68.3% men) with T2DM and NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. TyG index was calculated as previously reported: ln [fasting TGs (mg/dL) * FBG (mg/dL)/2]. The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and ischemia-driven revascularization., Results: TyG index was significantly higher in patients with a primary endpoint event compared with those without. Multivariate Cox proportional hazards analysis showed that 1-unit increase of TyG index was independently associated with higher risk of primary endpoint, independent of other risk factors [hazard ratio (HR) 3.208 per 1-unit increase, 95% confidence interval (CI) 2.400-4.289, P < 0.001]. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for adverse prognosis [AUC: baseline risk model, 0.800 vs. baseline risk model + TyG index, 0.856, P for comparison < 0.001; category-free net reclassification improvement (NRI) 0.346, P < 0.001; integrated discrimination improvement (IDI) 0.087, P < 0.001]., Conclusions: Increased TyG index is a significant predictor of adverse prognosis in patients with T2DM and NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether interventions for TyG index have a positive impact on improving clinical prognosis.

Background Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab non-ST-segment-elevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both C-reactive protein and troponin T were reduced in the active treatment arm. In this follow-up study, an aptamer-based proteomic approach was employed to discover additional plasma proteins modulated by tocilizumab treatment to gain novel insights into the effects of this therapeutic approach. Methods and Results Plasma from percutaneous coronary intervention-treated patients, 24 in the active intervention and 24 in the placebo-control arm, drawn 48 hours postrandomization were randomly selected for analysis with the SOMAscan assay. Employing slow off-rate aptamers, the relative abundance of 1074 circulating proteins was measured. Proteins identified as being significantly different between groups were subsequently measured by enzyme immunoassay in the whole trial cohort (117 patients) at all time points (days 1-3 [7 time points] and 3 and 6 months). Five proteins identified by the SOMAscan assay, and subsequently confirmed by enzyme immunoassay, were significantly altered by tocilizumab administration. The acute-phase proteins lipopolysaccharide-binding protein, hepcidin, and insulin-like growth factor-binding protein 4 were all reduced during the hospitalization phase, as was the monocyte chemoattractant C-C motif chemokine ligand 23. Proteinase 3, released primarily from neutrophils, was significantly elevated. Conclusions Employing the SOMAscan aptamer-based proteomics platform, 5 proteins were newly identified that are modulated by interleukin 6 antagonism and may mediate the therapeutic effects of tocilizumab in non-ST-segment-elevation myocardial infarction.

Background: Visfatin is an adipokine that related with the inflammation in atherosclerosis and the destabilization of atherosclerotic plaque. The aim of this study was to observe the relationship between visfatin and major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients., Methods: We enrolled a total of 238 patients (183 AMI and 55 control) who underwent coronary angiography. Patients with AMI were followed for an average of 19.3 months and 159 patients were finally included in the study., Results: It was observed patients with AMI had higher serum visfatin levels than controls. The total incidence of MACEs was 11.32% (18/159) in AMI patients. After calculation of the Youden index, the best cut-off value of visfatin on the curve of receiver-operating characteristic was 8.799 ng/mL for predicting the occurrence of MACEs. The occurrence of MACEs was elevated in high-visfatin group (≥8.799 ng/mL) compared with low-visfatin group (≤8.799 ng/mL). The time to MACEs was correlated with visfatin (HR = 1.235, 95%CI 1.051-1.451, P = 0.01) and high-visfatin group had an earlier time to MACEs and a shorter time of cumulative survival., Conclusions: Increased serum visfatin levels were observed in AMI patients, and correlated with an earlier onset and higher incidence of MACEs.

An 84-year-old woman complaining of acute-onset chest distress for 2 hours was referred to the Department of Cardiology, Guangzhou Red Cross Hospital, China. A physical examination showed signs of acute pulmonary edema with considerably elevated blood pressure of 186/120 mmHg. An electrocardiogram showed ST segment depression in leads I, II, and III, and from V4 to V6. A laboratory test showed markedly elevated creatine, high-sensitivity cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels. Echocardiography showed a mildly enlarged left ventricle with an ejection fraction of 43%. The patient was diagnosed with acute coronary syndrome, non-ST segment elevation myocardial infarction, and Killip 3 grade heart function. The non-ST segment elevation myocardial infarction Global Registry of Acute Coronary Events score was 156. Emergency coronary angiography showed severe three-vessel disease with a global ejection fraction of 50% based on left ventricular angiography. Selective renal artery angiography was performed and major stenosis at the ostia in both renal arteries was found. We did not touch the coronary artery, but performed intervention of the renal artery by implanting two bare metal stents in both ostia of bilateral renal arteries. An unexpected clinical benefit was obtained.

Whether ST-segment (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) should be regarded as distinct pathophysiological entities is a matter of debate. We tested the hypothesis that peripheral blood gene-expression profiles at presentation distinguish STEMI from NSTEMI. We performed a case-control study collecting whole-blood from 60 STEMI and 58 NSTEMI (defined according to the third universal definition of MI) consecutive patients on hospital admission. We used RNA-sequencing for the discovery phase, comparing 15 STEMI vs. 15 NSTEMI patients, matched for age, sex, and cardiovascular risk factors, and quantitative PCR in the remaining unmatched patients for validating top-significant genes. Gene-level differential expression analysis identified significant differences in the expression of 323 genes: 153 genes withstood correction for admission cardiac troponin I (cTnI), differentiating the two conditions independently of myocardial necrosis extent. Functional annotation analysis uncovered divergent modulation in leukocyte and platelet activation, cell migration, and mitochondrial respiratory processes. Linear regression analysis revealed gene expression patterns on admission predicting infarct size, as indexed by cTnI peak (R 2  = 0.58-0.75). Our results unveil distinctive pathological traits for these two MI subtypes and provide insights into the early assessment of injury extent. This could translate into RNA-based disease-specific biomarkers for precision diagnosis and risk stratification.

Lowering low-density lipoprotein (LDL-C) and triglyceride (TG) levels form the cornerstone approach of cardiovascular risk reduction, and a higher high-density lipoprotein (HDL-C) is thought to be protective. However, in acute myocardial infarction (AMI) patients, higher admission LDL-C and TG levels have been shown to be associated with better clinical outcomes - termed the 'lipid paradox'. We studied the relationship between lipid profile obtained within 72 hours of presentation, and all-cause mortality (during hospitalization, at 30-days and 12-months), and rehospitalization for heart failure and non-fatal AMI at 12-months in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated by percutaneous coronary intervention (PCI). We included 11543 STEMI and 8470 NSTEMI patients who underwent PCI in the Singapore Myocardial Infarction Registry between 2008-2015. NSTEMI patients were older (60.3 years vs 57.7 years, p < 0.001) and more likely to be female (22.4% vs 15.0%, p < 0.001). In NSTEMI, a lower LDL-C was paradoxically associated with worse outcomes for death during hospitalization, within 30-days and within 12-months (all p < 0.001), but adjustment eliminated this paradox. In contrast, the paradox for LDL-C persisted for all primary outcomes after adjustment in STEMI. For NSTEMI patients, a lower HDL-C was associated with a higher risk of death during hospitalization but in STEMI patients a lower HDL-C was paradoxically associated with a lower risk of death during hospitalization. For this endpoint, the interaction term for HDL-C and type of MI was significant even after adjustment. An elevated TG level was not protective after adjustment. These observations may be due to differing characteristics and underlying pathophysiological mechanisms in NSTEMI and STEMI.

Background: Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care., Method: Older patients undergoing invasive management for NSTEACS were recruited to the ICON-1 biomarker study (NCT01933581). Peripheral blood mononuclear cells (PBMC) were recovered on 153 patients. DNA was isolated and mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio (T/S ratio), and a telomere repeat amplification assay was used to assess TA during index presentation with NSTEACS. Primary clinical outcomes consisted of death, myocardial infarction (MI), unplanned revascularisation, stroke and significant bleeding recorded at 1 year. TL and TA were divided into tertile groups for analysis. Cox proportional hazards regression was performed. Ordinal regression was performed to evaluate the relationship between TL and TA and traditional cardiovascular risk factors at baseline., Results: 298 patients were recruited in the ICON-1 study of which 153 had PBMC recovered. The mean age was 81.0 ± 4.0 years (64% male). Mean telomere length T/S ratio was 0.47 ± 0.25 and mean TA was 1.52 ± 0.61 units. The primary composite outcome occurred in 44 (28.8%) patients. There was no association between short TL or low TA and incidence of the primary composite outcome (Hazard Ratio [HR] 1.50, 95% Confidence Interval [CI] 0.68-3.34, p = 0.32 and HR 1.33, 95% CI 0.52-3.36, p = 0.51 respectively)., Conclusion: TL and TA are not found to be associated with the incidence of adverse outcomes in older patients presenting with NSTEACS undergoing invasive care., Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT01933581., Competing Interests: The authors have declared that no competing interests exist. VK has received research funding from NIHR BRC Newcastle, AstraZeneca, and British Heart Foundation. WQ is salaried by Sanofi Genzyme. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Circulating endothelial cells (CEC) may be used to find new strategies for the early di-agnosis of cardiovascular diseases. The major objective of the project is to broaden knowledge of CEC biology by determining their phenotypic characteristics. The additional aim is to clarify whether on the basis of these information it is possible to identify the origin of CEC release (from various cardiovascular compartments)., Methods: Circulating endothelial cells were collected from arterial blood prior to angiography, as well as from arterial and venous blood obtained after angiography/coronary angioplasty, from 18 patients with non-ST-segment elevation myocardial infarction (NSTEMI). CECs were quantified by flow cytometry and defined as Syto16 (dye)+, CD45dim/neg, CD31+ and CD146+. The additional CD36+ was establish as a marker of endothelial cells released from small vessels of the microcirculation., Results: The total number of CECs increased significantly after the percutaneous transluminal coronary angioplasty (PTCA) in the arterial system. Number of CECs isolated at similar time points (after invasive procedure) did not differ significantly between arteries and veins, but the number of CD36+ CECs after coronary angioplasty was significantly higher in the venous system, than in the arterial system., Conclusions: The number of CD36+ in artery samples obtained after coronary angioplasty (PTCA) had tendency to be decreased (in comparison to the sample obtained before angiography). It was major difference between those who had PTCA performed vs. those who had not.

Objectives: The endocannabinoid system modulates coronary circulatory function and atherogenesis. The two major endocannabinoids (eCB), 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (AEA), are increased in venous blood from patients with coronary artery disease (CAD). However, given their short half-life and their autocrine/paracrine mechanism of action, eCB levels in venous blood samples might not reflect arterial or coronary eCB concentrations. The aim of this cross-sectional study was to identify the local concentration profile of eCB and to detect whether and how this concentration profile changes in CAD and NSTEMI versus patients without CAD., Methods and Results: 83 patients undergoing coronary angiography were included in this study. Patients were divided into three groups based on their definite diagnosis of a) no CAD, b) stable CAD, or c) non-ST-segment elevation myocardial infarction (NSTEMI). Blood was drawn from the arterial sheath and the aorta in all patients and additionally distal to the culprit coronary lesion in CAD- and NSTEMI patients. 2-AG levels varied significantly between patient groups and between the sites of blood extraction. The lowest levels were detected in patients without CAD; the highest 2-AG concentrations were detected in NSTEMI patients and in the coronary arteries. Peripheral 2-AG levels were significantly higher in NSTEMI patients (107.4 ± 28.4 pmol/ml) than in CAD- (17.4 ± 5.4 pmol/ml; p < 0.001), or no-CAD patients (23.9 ± 7.1 pmol/ml; p < 0.001). Moreover, coronary 2-AG levels were significantly higher in NSTEMI patients than in CAD patients (369.3 ± 57.2 pmol/ml vs. 240.1 ± 25.3 pmol/ml; p = 0.024)., Conclusions: 2-AG showed significant variability in arterial blood samples drawn from distinct locations. Possibly, lesional macrophages synthesise 2-AG locally, which thereby contributes to endothelial dysfunction and local inflammation., Competing Interests: The authors have declared that no competing interests exist.

Background: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome., Objectives: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI)., Methods: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR., Results: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis., Conclusion: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis., (© 2019 Aix-Marseille University. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc.)

Background/aims: The aim of this study was to investigate useful cardiac biomarkers in the differential diagnosis of acute pulmonary embolism (APE) with troponin elevation from acute non-ST elevation myocardial infarction (NSTEMI)., Methods: A total of 771 consecutive NSTEMI patients with D-dimer measurements and 90 patients with troponin-I (TnI) elevation out of 233 APE patients were enrolled, and cardiac biomarkers were compared., Results: D-dimer elevation was noted in 382 patients with NSTEMI (49.5%), and TnI elevation was noted 90 out of 233 APE patients (38.6%). Unnecessary coronary angiography was performed in 10 patients (11.1%) among 90 APE patients with TnI elevation. D-dimer was significantly elevated in APE than in NSTEMI (9.9 ± 11.6 mg/L vs. 1.8 ± 4.3 mg/L, p < 0.001), whereas TnI was significantly elevated in NSTEMI (22.4 ± 41.5 ng/mL vs. 0.7 ± 1.4 ng/mL, p < 0.001). D-dimer/TnI ratio was significantly higher in APE than in NSTEMI (50.6 ± 85.3 vs. 1.6 ± 5.7, p < 0.001). On receiver operation characteristic curve analysis, the optimal cut-off value for differentiating APE from NSTEMI was 1.12 mg/L for D-dimer (sensitivity 81.1%, specificity 70.2%), 0.72 ng/mL for TnI (sensitivity 80.6%, specificity 78.9%), and 1.82 for D-dimer/TnI ratio (sensitivity 93.3%, specificity 86.6%)., Conclusion: D-dimer/TnI ratio would be a simple and useful parameter for differentiating APE with cardiac troponin elevation from NSTEMI. Optimal cardiovascular imaging to identify APE should be considered in patients with D-dimer/ TnI ratio > 1.82 before performing coronary angiography to avoid unnecessary invasive procedure.

Introduction: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs., Methods and Analysis: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation., Ethics and Dissemination: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals., Competing Interests: Competing interests: MT received non-financial support from Roche, Abbott and Siemens during the conduct of the study; personal fees from Japan Medical Journal, outside the submitted work. AC has received honoraria from Abbott Diagnostics and AstraZeneca. NM has received honoraria and consultancy from Abbott Diagnostics, Roche Diagnostics and Singulex. TAF reports personal fees from Meiji Seika, grants and personal fees from MSD, personal fees from Pfizer, outside the submitted work. NW has received research funds from the Japanese Ministry of Health Labor and Welfare, the Japanese Ministry of Education, Science, and Technology and National Center of Neurology and Psychiatry, Intramural Research Grant for Neurological and Psychiatric Disorders. He has also received royalties from Sogensha and Akatsuki., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To investigate factors predicting the onset of major adverse cardiovascular and cerebrovascular events (MACCEs) after primary percutaneous coronary intervention (pPCI) for patients with non-ST-segment elevation infarction (NSTEMI) and single concomitant chronic total occlusion (CTO). Neutrophil gelatinase-associated lipocalin (NGAL) and glycosylated hemoglobin (HbA1c) both play essential role in cardiovascular and cerebrovascular homoeostasis. However, current knowledge of its predictive prognostic value is limited.422 patients with NSTEMI and CTO (59.7 ± 12.4 years, 74.2% men) who underwent successful pPCI were enrolled and followed for 2 years. Multivariate cox regression analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the factors predicting MACCEs.140 patients (33.2%) experienced MACCEs in the follow-up period. Multivariate cox regression analysis found when we process the model with NGAL at admission, low left ventricular ejection fraction (LVEF, HR = 0.963, 95% CI 0.940 to 0.987, P = .003) and fasting blood glucose (HR = 1.078, 95% CI 1.002 to 1.159, P = .044), but not NGAL at admission, were independent predictors of 2 years MACCEs. While HbA1C (HR = 1.119, 95% CI 1.014 to 1.234, P = .025), LVEF (HR = 0.963, 95% CI 0.939 to 0.987, P = .003), estimated glomerular filtration rate (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) and NGAL value 7 day (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) showed their predictive value in another model. ROC analysis indicated NGAL 7 day (AUC = 0.680, P = .0054 and AUC = 0.622, P = .0005) and LVEF (AUC = 0.691, P = .0298 and AUC = 0.605, P = .0021) could predict both in-hospital and 2 years MACCEs, while higher NGAL at admission could only predict poorer in-hospital prognosis (AUC = 0.665, P = .0103). Further analysis showed the prognostic value of NGAL was particularly remarkable among those HbA1C<6.5%.Patients with NSTEMI and single concomitant CTO receiving pPCI with higher NGAL on 7 days during hospitalization are more likely to suffer 2 years MACCEs, particularly in those with lower HbA1C.

Background: The study was designed to investigate lipid profile and SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI)., Methods: 311 patients with NSTEMI were enrolled. The demographic, clinical data, blood samples and SYNTAX score were documented. The Pearson linear correlation was used to detect confounding factors linearly correlated with SYNTAX score. The significantly correlated confounding factors were put into the multiple linear regressions., Results: The Pearson linear correlation showed that high-density lipoprotein- cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly correlated with Syntax Score (r = - 0.119, P = 0.044 and r = - 0.182, P = 0.002, respectively). The multiple linear regressions for Syntax Score were built using HDL-C and ApoA1, respectively. After the adjustment of other significantly correlated confounding factors such as white blood cell count (WBC), myohemoglobin (MB), glutamic-oxalacetic transaminase (AST) and creatinine, the ApoA1 still showed significant association with Syntax Score (β = - 0.151, P = 0.028). The area under curve was (AUC) 0.624 and the optimal cutoff value is 1.07 g/L when using ApoA1 to predict moderate and severe coronary artery lesions. The patients with ApoA1 ≥ 1.07 g/L and < 1.07 g/L have the Syntax Scores of 12.21 ± 11.58 and 16.33 ± 11.53, respectively (P = 0.001)., Conclusions: The ApoA1 is the only lipid factor significantly associated with complexity of coronary artery lesion in patients with NSTEMI, the patients with ApoA1 < 1.07 g/L may have more complex coronary artery lesions.

Background Cardiac troponin T ( cTnT ) is seen in many other conditions besides myocardial infarction, and recent studies demonstrated distinct forms of cTnT . At present, the in vivo formation of these different cTnT forms is incompletely understood. We therefore performed a study on the composition of cTnT during the course of myocardial infarction, including coronary venous system sampling, close to its site of release. Methods and Results Baseline samples were obtained from multiple coronary venous system locations, and a peripheral artery and vein in 71 non- ST -segment-elevation myocardial infarction patients. Additionally, peripheral blood was drawn at 6- and 12-hours postcatheterization. cTnT concentrations were measured using the high-sensitivity- cTnT immunoassay. The cTnT composition was determined via gel filtration chromatography and Western blotting in an early and late presenting patient. High-sensitivity - cTnT concentrations were 28% higher in the coronary venous system than peripherally (n=71, P<0.001). Coronary venous system samples demonstrated cT n T-I-C complex, free intact cTnT , and 29 kD a and 15 to 18 kD a cTnT fragments, all in higher concentrations than in simultaneously obtained peripheral samples. While cT n T-I-C complex proportionally decreased, and disappeared over time, 15 to 18 kD a cTnT fragments increased. Moreover, cT n T-I-C complex was more prominent in the early than in the late presenting patient. Conclusions This explorative study in non- ST -segment-elevation myocardial infarction shows that cTnT is released from cardiomyocytes as a combination of cT n T-I-C complex, free intact cTnT , and multiple cTnT fragments indicating intracellular cTnT degradation. Over time, the cT n T-I-C complex disappeared because of in vivo degradation. These insights might serve as a stepping stone toward a high-sensitivity- cTnT immunoassay more specific for myocardial infarction.

Objectives: Copeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters., Setting: We performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours., Participants: 449 patients were included, in whom 12% had NSTEMI. CPO occurred <2 hours from ED presentation in 160, between 2 and 4 hours in 143 and >4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281)., Measures: Diagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured., Results: Diagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO <2 hours, the choice of a threshold value of 14 ng/L for HS-cTnT resulted in three false negative (Sensitivity 80%(95% CI 51% to 95%); specificity 85% (95% CI 78% to 90%); 79% of correctly ruled out patients) and that of 5 ng/L in two false negative (sensitivity 87% (95% CI 59% to 98%); specificity 58% (95% CI 50% to 66%); 52% of correctly ruled out patients). The addition of copeptin to HS-cTnT induced a decrease of misclassified patients to 1 in patients with CPO <2 hours (sensitivity 93% (95% CI 66% to 100%); specificity 41% (95% CI 33% to 50%))., Conclusion: A single measurement of HS-cTn, alone or in combination with copeptin at admission, seems not safe enough for ruling out NSTEMI in very early presenters (with CPO <2 hours)., Trial Registration Number: DC-2009-1052., Competing Interests: Competing interests: CC-G, PR and CM received honorarias and lecture fees from Roche Diagnostics andThermofisher Scientific., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The underlying mechanisms by which cystatin C affects cardiovascular disease (CVD) are not very clear. Metabolic syndrome (MetS) is a cluster of risk factors that increase the risk of CVD. Here, we aimed to investigate the association of cystatin C with metabolic syndrome and cardiovascular outcomes in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with preserved renal function., Methods: In total, 422 NSTE-ACS patients with preserved renal function were enrolled to examine the association of cystatin C with MetS. MetS was defined based on the NCEP-ATP-III guidelines. Major adverse cardiovascular events (MACEs) were also evaluated, which included cardiac death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), heart failure, and nonfatal stroke. All patients underwent a 12-month follow-up for MACEs after admission., Results: Cystatin C was significantly correlated with metabolic risk factors and inflammation markers. The prevalence of MetS and MACEs correlated with cystatin C levels. Cystatin C showed a strong diagnostic performance for cardiovascular risk factors and outcomes in ROC analysis. After adjustment for multiple risk factors, cystatin C level was independently associated with MetS (OR 2.299, 95% CI 1.251-4.225, and P = 0.007). During a 12-month follow-up, the patients with high cystatin C level and MetS had higher incidence of MACEs (Log-rank = 24.586, P < 0.001) and cardiac death (Log-rank = 9.890, P = 0.020) compared to the others. Multivariate Cox analysis indicated that cystatin C level was an independent predictor of MACEs (HR 2.609, 95% CI 1.295-5.257, and P = 0.007)., Conclusion: Cystatin C may be an independent predictor of metabolic syndrome and therefore valuable for management of NSTE-ACS patients. Further multicenter, large-scale studies are required to assess the implication of these results.