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1.
Clin Transl Sci ; 17(5): e13823, 2024 May.
Article in English | MEDLINE | ID: mdl-38771157

ABSTRACT

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 αIIbß3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbß3. 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.


Subject(s)
Autophagy , Beclin-1 , Blood Platelets , Non-ST Elevated Myocardial Infarction , Platelet Activation , Thrombosis , Humans , Beclin-1/metabolism , Male , Female , Non-ST Elevated Myocardial Infarction/blood , Middle Aged , Aged , Prospective Studies , Blood Platelets/metabolism , Thrombosis/blood , Thrombosis/metabolism , Coronary Angiography , Platelet Aggregation , Case-Control Studies , Tomography, Optical Coherence , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
2.
Cardiovasc Diabetol ; 23(1): 147, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685054

ABSTRACT

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.


Subject(s)
Biomarkers , Blood Glucose , Diabetes Mellitus, Type 2 , Hospital Mortality , Insulin Resistance , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/complications , Male , Female , Middle Aged , Aged , Risk Assessment , Prognosis , Biomarkers/blood , Retrospective Studies , Time Factors , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/diagnosis , Blood Glucose/metabolism , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/therapy , Risk Factors , Body Mass Index , Predictive Value of Tests , Triglycerides/blood , Aged, 80 and over
3.
Thromb Haemost ; 124(6): 501-516, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38158199

ABSTRACT

BACKGROUND: East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. OBJECTIVES: We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. METHODS: In a prospective study in the United Kingdom and Korea, blood samples from patients (n = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. RESULTS: EA patients showed reduced OT (longer OT) compared to W (646 seconds [470-818] vs. 436 seconds [320-580], p < 0.001), with similar LT. In STEMI, OT (588 seconds [440-759] vs. 361 seconds [274-462], p < 0.001) and LT (1,854 seconds [1,389-2,729] vs. 1,338 seconds [1,104-1,788], p < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541-866] vs. 580 seconds [474-712], p < 0.001) and LT shorter (1519 seconds [1,058-2,508] vs. 1,898 seconds [1,614-2,806], p = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43-9.57, p = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. CONCLUSION: EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.


Subject(s)
Acute Coronary Syndrome , Asian People , Hemorrhage , Non-ST Elevated Myocardial Infarction , White People , Humans , Male , Female , Middle Aged , Prospective Studies , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/ethnology , Acute Coronary Syndrome/epidemiology , Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/ethnology , Hemorrhage/blood , Republic of Korea/epidemiology , Risk Factors , United Kingdom/epidemiology , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/ethnology , ST Elevation Myocardial Infarction/epidemiology , Thrombosis/blood , Thrombosis/etiology , Myocardial Infarction/blood , Myocardial Infarction/ethnology , Myocardial Infarction/epidemiology , Fibrinolysis , East Asian People
4.
Clin Biochem ; 104: 22-29, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35181290

ABSTRACT

PURPOSE: The study sought to assess the performance of D-dimer testing for the diagnosis of acute coronary syndrome (ACS) and prediction of outcomes in patients admitted for suspected myocardial infarction (MI). RESULTS: A total of 3,557 patients with suspected ACS presenting to a single center with a broad range of symptoms including atypical chest pain were retrospectively recruited between 02/2012-01/2019. Of the study cohort, 435 patients had unstable angina (UA), 420 non-ST-segment elevation myocardial infarction (NSTEMI), 22 ST-segment elevation myocardial infarction (STEMI), and 2,680 non-coronary chest pain. Plasma D-dimer concentrations in patients with hs-cTnT > 14 ng/L differed significantly from those with hs-cTnT < 14 ng/L (1.5 ± 3.6 mg/L vs. 0.5 ± 0.8 mg/L; p < 0.0001). Positive predictive value for a final diagnosis of ACS increased proportionally to rising D-dimer concentrations. The area under the curve (AUC) to discriminate STEMI from non-coronary chest pain (AUC 0.729, 95% confidence interval [CI] 0.71-0.75) was moderate and differed not significantly to UA (AUC 0.595, 95% CI 0.58-0.61; p = 0.0653). During a median follow-up of 29 months, higher D-dimer was associated with a significantly increased risk of recurrent MI (quartile 4 vs. 1: hazard ratio [HR], 6.9 [95% CI 1.2-39.9]; p < 0.0001) and higher all-cause mortality (HR, 17.4 [95% CI 4.3-69.9]; p < 0.0001). D-dimer was an independent predictor of all-cause mortality (p < 0.0001) and subsequent MI events (p = 0.0333). CONCLUSIONS: D-dimer testing revealed great potential to provide independent prognostic information on recurrent MI and all-cause mortality. However, D-dimers do not improve the diagnostic performance except if values exceed the 95th percentile.


Subject(s)
Fibrin Fibrinogen Degradation Products , Myocardial Infarction , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Angina, Unstable/blood , Angina, Unstable/diagnosis , Chest Pain/diagnosis , Emergency Service, Hospital , Fibrin Fibrinogen Degradation Products/analysis , Humans , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Retrospective Studies , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnosis
5.
Cardiovasc Diabetol ; 21(1): 11, 2022 01 19.
Article in English | MEDLINE | ID: mdl-35045846

ABSTRACT

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.


Subject(s)
Acute Coronary Syndrome/therapy , Diabetes Mellitus, Type 2/blood , Glycated Hemoglobin/metabolism , Non-ST Elevated Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Aged , Beijing , Biomarkers/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Female , Humans , Ischemic Stroke/etiology , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Predictive Value of Tests , Recurrence , Retreatment , Retrospective Studies , Risk Assessment , Risk Factors , Stents , Time Factors , Treatment Outcome
6.
Turk Kardiyol Dern Ars ; 49(8): 666-674, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34881705

ABSTRACT

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.


Subject(s)
Non-ST Elevated Myocardial Infarction/blood , Rheumatoid Factor/blood , ST Elevation Myocardial Infarction/blood , Adult , Aged , Biomarkers/blood , Cardiovascular Diseases/mortality , Cholesterol/blood , Coronary Angiography , Coronary Artery Disease/etiology , Female , Humans , Logistic Models , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Prospective Studies , Severity of Illness Index , Stroke Volume , Troponin T/blood , Ventricular Function, Left/physiology
7.
Medicine (Baltimore) ; 100(51): e27779, 2021 Dec 23.
Article in English | MEDLINE | ID: mdl-34941030

ABSTRACT

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.


Subject(s)
Circulating MicroRNA , MicroRNAs/blood , Myocardial Infarction/diagnosis , Biomarkers/blood , Chest Pain/etiology , Humans , MicroRNAs/genetics , Myocardial Infarction/blood , Myocardial Infarction/genetics , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
8.
Cardiovasc Diabetol ; 20(1): 211, 2021 10 19.
Article in English | MEDLINE | ID: mdl-34666746

ABSTRACT

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.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/blood , Glycated Hemoglobin/metabolism , Non-ST Elevated Myocardial Infarction/blood , ST Elevation Myocardial Infarction/blood , Aged , Biomarkers/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Diabetes Mellitus/therapy , Female , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/therapy , Patient Admission , Predictive Value of Tests , Prognosis , Registries , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Singapore/epidemiology , Time Factors
10.
Clin Biochem ; 98: 17-23, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34496288

ABSTRACT

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.


Subject(s)
Blood Proteins/metabolism , Non-ST Elevated Myocardial Infarction/blood , Registries , ST Elevation Myocardial Infarction/blood , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged
12.
Open Heart ; 8(1)2021 05.
Article in English | MEDLINE | ID: mdl-33972404

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Histones/blood , Non-ST Elevated Myocardial Infarction/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Troponin T/blood , Young Adult
13.
Angiology ; 72(9): 889-895, 2021 10.
Article in English | MEDLINE | ID: mdl-33827291

ABSTRACT

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.


Subject(s)
Contrast Media/administration & dosage , Inflammation/diagnosis , Kidney Diseases/chemically induced , Non-ST Elevated Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , Adult , Aged , Blood Platelets , Female , Humans , Inflammation/blood , Kidney Diseases/blood , Kidney Diseases/diagnosis , Lymphocyte Count , Lymphocytes , Male , Middle Aged , Neutrophils , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnostic imaging , Patient Admission , Platelet Count , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
14.
Am J Med Sci ; 361(6): 759-764, 2021 06.
Article in English | MEDLINE | ID: mdl-33892919

ABSTRACT

BACKGROUND: Identifying a novel biomarker may contribute to detection of vulnerable plaque in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). The aim of this study was to investigate the relationship between serum platelet-derived growth factor (PDGF) and vulnerable plaque in patients with moderate and low risk of NSTE-ACS. METHODS: A total of 65 moderate- and low-risk NSTE-ACS patients with 50-90% coronary stenosis were divided into a vulnerable plaque group (n=46) and a stable plaque group (n=19) according to intravascular ultrasound (IVUS) examinations. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and serum PDGF were measured. Plaque characteristics and components were analyzed using gray-scale and iMap-IVUS. Correlation was performed between plaque characteristics and ACS markers. Logistic regression analysis was applied to determine risk factors. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value. RESULTS: Patients with vulnerable plaque had visible higher levels of TG, LDL-C and PDGF (P < 0.05). There were significant differences in minimal lumen area (MLA), plaque area, plaque burden, fibrotic (FI), clipidic (LI) and necrotic core (NC) between the two groups (P < 0.05). PDGF was weakly correlated with plaque burden (R = 0.428, P < 0.05), as well as moderately correlated with NC (R = 0.669, P < 0.05). Multivariate analysis showed that serum PDGF (OR 4.751, [95% CI 1.534-9.543], P = 0.05) was an independent risk factor of vulnerable plaque. The area under the curve (AUC) was 0.876 (95% CI 0.804-0.948, P=0.001). CONCLUSIONS: Serum PDGF could potentially predict vulnerable plaque in moderate and low risk of NSTE-ACS patients.


Subject(s)
Acute Coronary Syndrome/blood , Non-ST Elevated Myocardial Infarction/blood , Plaque, Atherosclerotic/blood , Platelet-Derived Growth Factor/metabolism , Acute Coronary Syndrome/diagnostic imaging , Aged , Biomarkers/blood , Coronary Angiography/methods , Female , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnostic imaging , Plaque, Atherosclerotic/diagnostic imaging , Predictive Value of Tests
15.
BMC Cardiovasc Disord ; 21(1): 202, 2021 04 21.
Article in English | MEDLINE | ID: mdl-33882836

ABSTRACT

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.


Subject(s)
Coronary Artery Disease/therapy , Natriuretic Peptide, Brain/blood , Non-ST Elevated Myocardial Infarction/therapy , Peptide Fragments/blood , Percutaneous Coronary Intervention , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cause of Death , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
16.
BMC Cardiovasc Disord ; 21(1): 175, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33849448

ABSTRACT

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.


Subject(s)
Atrial Fibrillation/etiology , C-Reactive Protein/analysis , Decision Support Techniques , Non-ST Elevated Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/diagnosis , Age Factors , Aged , Aged, 80 and over , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Biomarkers/blood , China , Female , Humans , Male , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/complications , Non-ST Elevated Myocardial Infarction/mortality , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/mortality , Time Factors
17.
Int J Mol Sci ; 22(6)2021 Mar 12.
Article in English | MEDLINE | ID: mdl-33809145

ABSTRACT

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.


Subject(s)
Arrhythmias, Cardiac/blood , Myocardial Infarction/blood , Pituitary Adenylate Cyclase-Activating Polypeptide/blood , ST Elevation Myocardial Infarction/genetics , Aged , Animals , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/surgery , Female , Glycated Hemoglobin/genetics , Heart Ventricles/metabolism , Heart Ventricles/pathology , Heart Ventricles/surgery , Humans , Male , Middle Aged , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/genetics , Non-ST Elevated Myocardial Infarction/physiopathology , Non-ST Elevated Myocardial Infarction/surgery , Percutaneous Coronary Intervention/adverse effects , Pituitary Adenylate Cyclase-Activating Polypeptide/genetics , Risk Factors , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/pathology , ST Elevation Myocardial Infarction/surgery , Swine , Treatment Outcome , Troponin/blood
18.
Molecules ; 26(4)2021 Feb 19.
Article in English | MEDLINE | ID: mdl-33669806

ABSTRACT

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.


Subject(s)
Acute Coronary Syndrome/blood , Calcium-Binding Proteins/blood , Extracellular Matrix Proteins/blood , Aged , Cohort Studies , Confounding Factors, Epidemiologic , Female , Hospital Mortality , Humans , Logistic Models , Male , Multivariate Analysis , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/mortality , Phosphorylation , Risk Factors , Matrix Gla Protein
20.
Rev. Soc. Bras. Clín. Méd ; 19(1): 37-41, março 2021. tab., graf.
Article in Portuguese | LILACS | ID: biblio-1361703

ABSTRACT

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)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Erythrocyte Indices , Percutaneous Coronary Intervention , Non-ST Elevated Myocardial Infarction/blood , Prognosis , Time Factors , Biomarkers , Survival Analysis , Multivariate Analysis , Predictive Value of Tests , Regression Analysis , Cohort Studies , Percutaneous Coronary Intervention/mortality , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/mortality , Heart Disease Risk Factors
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