Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction.

BACKGROUND: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment. METHODS: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008-2014. Blood samples were collected day 1-3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events. RESULTS: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI. CONCLUSIONS: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study.

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.

Systemic Immune Inflammation Index: A Novel Predictor of Contrast-Induced Nephropathy in Patients With Non-ST Segment Elevation Myocardial Infarction.

We investigated whether the systemic immune inflammation index (SII) on admission is an independent risk factor that predicts the development of contrast-induced nephropathy (CIN) in patients with non-ST segment elevation myocardial infarction (NSTEMI) who underwent percutaneous coronary intervention (PCI). A total of 429 patients with NSTEMI were enrolled in the study. Contrast-induced nephropathy was defined as an increase in serum creatinine level of ≥0.5 mg/dL or ≥25% above baseline within 72 hour after the procedure. Patients were divided into 2 groups: with and without CIN. Demographics, clinical risk factors, angiographic and laboratory parameters, CIN incidence, and SII score were compared between the 2 groups. Non-ST segment elevation myocardial infarction patients, who developed CIN, had higher glucose levels (P = .009), neutrophil counts (P < .001), platelet counts (P < .001), neutrophil-lymphocyte ratios (P < .001), high sensitivity C-reactive protein levels (P = .009), and SII levels (P < .001) than those who did not develop CIN. The receiver operating characteristic curve analysis showed that at a cutoff of 933.2, the value of SII exhibited 77.6% sensitivity and 69.2% specificity for detecting CIN. Our study showed that the SII levels on admission were independently associated with CIN development after PCI in patients with NSTEMI.

Valor prognóstico da amplitude de distribuição das hemácias em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST submetidos à intervenção coronariana percutânea / Prognostic value of red cell distribution width in ST-segment elevation myocardium infarction patients undergoing percutaneous coronary intervention

Objetivo: Determinar os valores da amplitude de distribuição das hemácias em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST submetidos à intervenção coronária percutânea primária e avaliar sua associação com resultados adversos. Métodos: Os níveis de amplitude de distribuição das hemácias foram medidos em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST antes da intervenção coronária percutânea primária e divididos conforme valor das amplitudes de distribuição das hemácias. Após a alta hospitalar, os pacientes foram acompanhados por até 3 anos para a ocorrência de eventos cardiovasculares adversos maiores e mortalidade a longo prazo. Resultados: Foram incluídos 893 pacientes com idade média de 60,7 (±12,5) anos, e 66,3% eram do sexo masculino. Na análise multivariada, a hemácia permaneceu como preditor independente de mortalidade a longo prazo. A área sob a curva para mortalidade a longo prazo foi de 0,64 (IC95% 0,61-0,67; p<0,0001). Amplitudes de distribuição das hemácias <13,3 tiveram valor preditivo negativo de 87,1% para mortalidade por todas as causas. Conclusão: Um valor elevado de amplitude de distribuição das hemácias é um preditor independente de mortalidade a longo prazo e eventos cardiovasculares adversos maiores em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST submetidos à intervenção coronária percutânea primária. Amplitudes de distribuição das hemácias baixas têm baixo tem um excelente valor preditivo negativo para mortalidade a longo prazo. (AU)

Objective: To determine red cell distribution width values in ST-elevation acute myocardial infarction patients undergoing primary percutaneous coronary intervention and to evaluate its association with adverse outcomes. Methods: Red cell distribution width levels were measured in ST-segment elevation myocardial infarction patients before primary percutaneous coronary intervention and divided into low and high red cell distribution width. After discharge, patients were followed for up to 3 years for the occurrence of long-term major adverse cardiovascular events and mortality. Results: A total of 893 patientes were with a mean age of 60.7 (±12.5) years, 66.3% were male. In multivariate analysis, the red cell distribution width remained as an independent predictor of long-term mortality. The area under the curve for long-term mortality was 0.64 (95%CI0.61-0.67; p<0.0001). Red cell distribution width<13.3 had a negative predictive value of 87.1% for all-cause mortality. Conclusion: High number of red cell distribution width is an independent predictor of long-term mortality and major adverse cardiovascular events in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. A low number of red cell distribution width has an excellent negative predictive value for long-term mortality. Patients with sustained elevated levels of red cell distribution width have worse outcomes at long-term follow-up. (AU)

Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction.

OBJECTIVE: High-sensitivity cardiac troponin assays (hs-cTn) aid in diagnosis of myocardial infarction (MI). These assays have lower specificity for non-ST Elevation MI (NSTEMI) in patients with renal disease. Our objective was to determine an optimized cutoff for patients with renal disease. METHODS: We conducted an a priori secondary analysis of a prospective FDA study in adults with suspected MI presenting to 29 academic urban EDs between 4/2015 and 4/2016. Blood was drawn 0, 1, 2-3, and 6-9 h after ED arrival. We recorded cTn and estimated glomerular filtrate rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation. The primary endpoint was NSTEMI (Third Universal Definition of MI), adjudicated by physicians blinded to hs-cTn results. We generated an adjusted hscTn rule-in cutoff to increase specificity. RESULTS: 2505 subjects were enrolled; 234 were excluded. Patients were mostly male (55.7%) and white (57.2%), median age was 56 years 472 patients [20.8%] had an eGFR <60 mL/min/1.73 m2. In patients with eGFR <15 mL/min/1.73 m2, a baseline rule-in cutoff of 120 ng/L led to a specificity of 85.0% and Positive Predictive Value (PPV) of 62.5% with 774 patients requiring further observation. Increasing the cutoff to 600 ng/L increased specificity and PPV overall and in every eGFR subgroup (specificity and PPV 93.3% and 78.9%, respectively for eGFR <15 mL/min/1.73m2), while increasing the number (79) of patients requiring observation. CONCLUSIONS: An eGFR-adjusted baseline rule-in threshold for the Siemens Atellica hs-cTnI improves specificity with identical sensitivity. Further study in a prospective cohort with higher rates of renal disease is warranted.

Predictive accuracy of lymphocyte-to-monocyte ratio and monocyte-to-high-density-lipoprotein-cholesterol ratio in determining the slow flow/no-reflow phenomenon in patients with non-ST-elevated myocardial infarction.

OBJECTIVE: To investigate whether inflammation based scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) predict the slow flow (SF)/no-reflow (NR) phenomenon comparatively in patients with non-ST-elevated Myocardial Infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). METHODS: Current study is retrospective designed and includes 426 NSTEMI patients (mean age of 56.8 ± 11.4 years). The patients were grouped into non slow flow/no-reflow and slow flow/no-reflow groups according to postintervention thrombolysis in myocardial infarction flow grade. RESULTS: The slow flow/no-reflow group had significantly higher MHR and lower LMR values than the non slow flow/no-reflow group (P < 0.01 and P < 0.01, respectively). Lower LMR [odds ratio (OR): 0.659, P < 0.01] and higher MHR (OR: 1.174, P = 0.04) were independent predictors of slow flow/no-reflow phenomenon in model 1 and 2 multivariate analyses, respectively. Furthermore, left ventricular ejection fraction (LVEF) (OR: 0.934, P = 0.01; OR: 0.930, P < 0.01), smoking (OR: 2.279, P = 0.03; OR: 2.118, P = 0.04), Syntax score (1.038, P = 0.04; 1.046, P = 0.01) and high thrombus grade (OR: 7.839, P < 0.01; OR: 8.269, P < 0.01), independently predicted the slow flow/no-reflow development in both multivariate analysis models, respectively. The predictive performance of LMR and MHR was not different (P = 0.88), but both predictive powers were superior to NLR (P < 0.01 and P = 0.03, respectively). CONCLUSION: The MHR and LMR may be useful inflammatory biomarkers for identifying high-risk individuals for the development of slow flow/no reflow in NSTEMI patients who underwent PCI.

Value of C-Reactive Protein/Albumin Ratio in Predicting the Development of Contrast-Induced Nephropathy in Patients With Non-ST Elevation Myocardial Infarction.

Contrast-induced nephropathy (CIN) accounts for about 10% of all hospital-acquired acute kidney injury. We aimed to assess the role of the combination of 2 inflammatory biomarkers, the C-reactive protein (CRP)/albumin ratio (CAR), in the development of CIN after percutaneous coronary intervention (PCI) in patients with non-ST-elevation myocardial infarction (NSTEMI). Patients with NSTEMI (n = 205) treated by PCI were classified according to the development of CIN. Both groups were compared according to clinical, laboratory, and demographic characteristics, including inflammatory biomarkers and specifically, CAR. Contrast-induced nephropathy was observed in 10.2% of patients. More advanced age, the presence of diabetes and dyslipidemia, left ventricular ejection fraction, and CAR correlated with the development of CIN. Analysis also showed a significant association between CAR and the development of CIN (CAR in CIN (+): 8.54 ± 8.48, range: 0.7-32, median: 7.13 vs CAR in CIN (-): 2.36 ± 3.01, range: 0.1-24, median: 1.33, P < .001). Multivariate logistic regression analysis showed the impact of CAR on the development of CIN (odds ratio: 1.244, 95% confidence interval: 1.102; 1.392, P < .01). We conclude that CAR, as a combination of 2 inflammatory biomarkers, is a more accurate predictor of CIN development compared with the single-marker assessment of albumin and CRP in the context of NSTEMI.

Association between Hemogram Parameters and Coronary Collateral Development in Subjects with Non-ST-Elevation Myocardial Infarction

SUMMARY OBJECTIVE Coronary collateral development (CCD) predicts the severity of coronary heart disease. Hemogram parameters, such as mean platelet volume (MPV), eosinophil, red cell distribution width, and platelet distribution width (PDW), are supposed novel inflammatory markers. We aimed to compare hemogram parameter values in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) with adequate or inadequate CCD. METHODS A total of 177 patients with NSTEMI undergoing coronary arteriography were enrolled and divided into two groups based on the development of CCD: one group with adequate CCD (n=88) and the other with impaired CCD (n=89). RESULTS Baseline demographics and clinical risk factors were similar between the groups. Hemogram parameters were not significantly different between the two groups. However, compared to the inadequate CCD group, the median PDW was significantly higher in the adequate CCD group, 17.6 (1.4) vs. 17.8 (1.6) p=0.004. In a multivariate analysis, PDW (p=0.001, 95% CI for OR: 0.489(0,319-0,750) was found to be significantly different in the adequate CCD group compared to the inadequate CCD group. Pearson's correlation analysis revealed that PDW was significantly correlated with the Rentrop score (r=0.26, p<0.001). CONCLUSIONS We suggest that since PDW is an index that is inexpensive and easy to assess, it could serve as a marker of CCD in patients with NSTEMI.

RESUMO OBJETIVO O desenvolvimento colateral coronariano (CCD) prediz a gravidade da doença coronariana. Parâmetros de hemograma como volume plaquetário médio (VPM), eosinófilo, largura de distribuição de glóbulos vermelhos e largura de distribuição de plaquetas (PDW) são supostos novos marcadores inflamatórios. Nosso objetivo foi comparar os valores do parâmetro hemograma em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST) com DCC adequado ou inadequado. MÉTODOS Um total de 177 pacientes com NSTEMI submetidos à arteriografia coronariana foram incluídos e divididos, com base no desenvolvimento de CCD, em dois grupos: grupo com CCD adequado (n = 88) e grupo com CCD alterado (n = 89). RESULTADOS Os dados demográficos e os fatores de risco clínicos basais foram semelhantes entre os grupos. Os parâmetros do hemograma não foram significativamente diferentes entre os dois grupos. Mas, em comparação com a mediana inadequada do grupo CCD, o PDW foi significativamente maior em CCD adequado de 17,6 (1,4) vs. 17,8 (1,6) p = 0,004. Na análise multivariada, PDW (p = 0,001, IC 95% para OR: 0,489 (0,319-0,750) foi significativamente diferente no grupo CCD adequado em comparação com o grupo CCD inadequado. A análise de correlação de Pearson revelou que PDW foi significativamente correlacionado com escore de aluguel (r = 0,26, p <0,001). CONCLUSÃO Sugerimos que, uma vez que a PDW é um índice barato e de fácil avaliação, pode servir como um marcador de DCC em pacientes com IAMSSST.

Safety and efficacy of bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes with positive biomarkers undergoing percutaneous coronary intervention: a report from the Acute Catheterization and Urgent Intervention Triage Strategy trial.

OBJECTIVES: There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. PATIENTS AND METHODS: We compared the net adverse clinical events [composite ischemia - (death, myocardial infarction, or unplanned ischemic revascularization) - or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy. RESULTS: Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis. CONCLUSION: Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.

Role of thrombin generation assays in the diagnosis of acute myocarditis and non-ST myocardial infarction.

Myocarditis and myocardial infarction share a common clinical characteristics despite significant differences in etiology and pathogenesis. Current guidelines recommend using cardiac magnetic resonance imaging (MRI) or endocardial biopsy for a definite diagnosis; however, these guidelines are not fully implemented due to the high cost and low availability. We used a thrombin generation assay and simple blood test to characterize both diseases. We conducted a cross-sectional study from April to December 2018. Patients with initial clinical suspicions of non-ST elevation myocardial infarction (NSTEMI) or myocarditis were eligible. All patients were recruited prior to anticoagulant treatment. Patients in both groups underwent acceptable standard clinical evaluation. Twenty-eight patients were enrolled; 12 patients in the NSTEMI group and 16 in the myocarditis group. Patients in the NSTEMI group were significantly older than those in the myocarditis group (64.25 ± 9.67 vs. 37.94 ± 19.66 years, p < 0.01, respectively) with a higher prevalence of hyperlipidemia, diabetes mellitus, and ischemic heart disease (p < 0.01 for all). There was no difference between the groups regarding INR, PT, aPTT, and serum levels of creatinine, urea, CPK, troponin, and fibrinogen. Endogenous thrombin potential (ETP), which represents the total thrombin concentration in the plasma, was significantly higher in the myocarditis group than in the NSTEMI group (2091.88 ± 336.41 vs. 1860.75 ± 438.02 nM × min, p < 0.03). Myocarditis and myocardial infarction have a different pattern of thrombin generation Thrombogram. The myocarditis group had significantly higher plasma ETP than the NSTEMI group. This finding requires further evaluation to define a numerical threshold, thus avoiding invasive or expensive assessment of myocarditis.

Characteristics of circulating endothelial cells obtained from non-ST-segment elevation myocardial infarction patients with additional diastolic dysfunction of left ventricle observed in echocardiography.

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.

The relationship between protein convertase subtilisin kexin type-9 levels and extent of coronary artery disease in patients with non-ST-elevation myocardial infarction.

BACKGROUND: Cardiovascular disease is one of the leading causes of death worldwide. According to the results of various studies, protein convertase subtilisin kexin type-9 (PCSK9) was determined as a novel risk factor for stable coronary artery disease. Few studies have investigated the relationship between PCSK9 levels and the severity of coronary artery disease in patients with acute coronary syndrome; thus, we herein aimed to investigate this relationship in patients with non-ST-elevation myocardial infarction (NSTEMI) who underwent coronary angiography. PATIENTS AND METHODS: Herein, 168 patients with NSTEMI were prospectively enrolled, and severity of atherosclerotic lesions was determined using SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX), Gensini and Jeopardy scores. Plasma PCSK9 levels, lipid parameters and C-reactive protein levels were measured after a 12-h fasting period. The relationship of PCSK9 levels and clinical and laboratory parameters of patients with their SYNTAX, Gensini and Jeopardy scores was investigated. RESULTS: Pearson correlation analysis showed a strong positive correlation between PCSK9 and the three scores (P < 0.001, r > 0.5 for all). In ROC analysis, a mid-high SYNTAX score of at least 25 was predicted with a sensitivity of 81% and a specificity of 63% when the PCSK9 level was higher than 52.8 ng/ml (area under a curve 0.76, P < 0.001). Multivariate linear regression analysis revealed that PCSK9, low-density lipoprotein cholesterol and creatinine levels were independent predictors of a high SYNTAX score. CONCLUSION: Taken together, high PCSK9 levels may be a risk factor for adverse events in patients with NSTEMI. Aggressive lipid-lowering therapies may benefit this group of patients.

Endocannabinoid 2-arachidonoylglycerol is elevated in the coronary circulation during acute coronary syndrome.

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.

Prognostic value of neutrophil gelatinase-associated lipocalin and glycosylated hemoglobin for non-ST-segment elevation myocardial infarction patients with single concomitant chronic total occlusion following primary percutaneous coronary intervention: A prospective observational study.

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 ±â€Š12.4 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.

Association of Cystatin C with Metabolic Syndrome and Its Prognostic Performance in Non-ST-Segment Elevation Acute Coronary Syndrome with Preserved Renal Function.

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.

Ticagrelor Does Not Improve Endothelial Dysfunction in Stable Survivors of Acute Coronary Syndrome.

BACKGROUND: Ticagrelor is an intriguing antiplatelet agent with a potentially beneficial impact on endothelial dysfunction and confers a mortality benefit beyond 1 month after acute coronary syndrome (ACS). However, little data exist on whether ticagrelor improves endothelial dysfunction in stable patients who survive the acute period and receive guideline-directed medical therapy. METHODS AND RESULTS: This study is a prospective, randomized, parallel, open-labeled study that enrolled 30-day survivors of non-ST-segment elevation ACS (NSTE-ACS). Forty patients with NSTE-ACS were randomly assigned to ticagrelor or clopidogrel groups. The primary end point was the change in the percentage brachial artery flow-mediated dilation (baFMD) from baseline. Baseline characteristics were not different between the 2 groups. The median time from the stent implantation to screening was 269 days. After 30 days of study medication administration, the change in the percentage baFMD value was similar between the ticagrelor and clopidogrel groups (-0.08 [1.42] vs 0.30 [1.69], P = .66). There was no difference in the change in high-sensitive C-reactive protein (-0.61 [1.48] vs -0.01 [0.57], P = .28); however, the change in platelet inhibition significantly differed (P2Y12 reaction units, -140.5 [49.5] vs -3.9 [51.4], P < .001). CONCLUSIONS: This dual time point baFMD study demonstrated that treatment with ticagrelor was not superior to clopidogrel for improving endothelial dysfunction in stabilized patients with NSTE-ACS.

Biomarker of Collagen Turnover (C-Terminal Telopeptide) and Prognosis in Patients With Non- ST -Elevation Acute Coronary Syndromes.

Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure ( HF ). We examined C-terminal telopeptide (beta- CT x) and the risk of cardiovascular death or new or worsening HF in non- ST -elevation acute coronary syndrome. Methods and Results We measured baseline serum beta- CT x, NT -pro BNP (N-terminal pro-B-type natriuretic peptide), hsTnT (high-sensitivity cardiac troponin T) and hs CRP (high-sensitivity C-reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non- ST -elevation acute coronary syndrome. The relationship between quartiles of beta- CT x and cardiovascular death or HF over a median follow-up time of 12 months was analyzed using adjusted Cox models. Higher beta- CT x levels identified a significantly higher risk of cardiovascular death/ HF (Q4 10.9% versus Q1 3.8%, Logrank P<0.001). After multivariable adjustment, beta- CT x in the top quartile (Q4) was associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 2.22 [1.50-3.27]) and its components (Q4 versus Q1: cardiovascular death: adjusted hazard ratio 2.48 [1.46-4.21]; HF : adjusted hazard ratio 2.04 [1.26-3.30]). In an adjusted multimarker model including NT -pro BNP , hsTnT, and hs CRP , beta- CT x remained independently associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 1.98 [1.34-2.93]) and its components. Beta- CT x correlated weakly with NT -pro BNP ( r=0.17, P<0.001) and left ventricular ejection fraction ( r=-0.05, P=0.008) and did not correlate with hsTnT ( r=0.02, P=0.20), or hs CRP ( r=-0.03, P=0.09). Conclusions Levels of beta- CT x, a biomarker of collagen turnover, were associated with cardiovascular death and HF in patients with non- ST -elevation acute coronary syndrome. This biomarker, which correlated only weakly or not significantly with traditional biomarkers of cardiovascular death and HF , may provide complementary pathobiological insight and risk stratification in these patients.

Trends of Cardiovascular Risk Factors in Patients With Acute Myocardial Infarction: Soroka Acute Myocardial Infarction II (SAMI II) Project.

CONCLUSIONS: The last decade, patients with AMI became older with increased burden of CVRFs. Framingham risk score increased among patients with NSTEMI and decreased in patients with STEMI. These trends impact on risk stratification and secondary prevention programs.

Assessment of Relationship Between C-Reactive Protein to Albumin Ratio and Coronary Artery Disease Severity in Patients With Acute Coronary Syndrome.

The association of coronary artery disease (CAD) severity with increased C-reactive protein (CRP) and decreased albumin levels has been reported. However, to our knowledge, no study has investigated the usefulness of the CRP to albumin ratio (CAR) in predicting intermediate-high SYNergy between Percutaneous Coronary Intervention with TAXus and cardiac surgery (SYNTAX) score (SS) and high SS II. Consecutive patients (n = 344) treated with percutaneous coronary intervention comprised the study population. The study population was divided into 2 groups according to SS >22 and mean SS II values, respectively. Patients with intermediate-high SS and high SS II had higher CAR than patients with low SS and SS II. History of diabetes mellitus, decreased albumin, lower left ventricular ejection fraction, and elevated CAR (odds ratio [OR]: 1.020; 95% confidence interval [CI], 1.009-1.031; P < .001) were independent predictors of high SS. The presence of hypertension, decreased hemoglobin and albumin levels, and increased CAR (OR: 1.014; 95% CI, 1.004-1.023; P < .001) were independent predictors of SS II. In receiver operating characteristic curve comparison, CAR was superior to CRP and albumin in prediction of intermediate-high SS, but only CRP in prediction of high SS II. The CAR calculated from the admission blood samples could be a useful parameter for predicting CAD severity using SS and SS II.