Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6 h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8 years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (ß - 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

[Correlation between serum growth differentiation factor 11 level and severity of coronary artery disease in patients with acute myocardial infarction].

Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

Serum ACSL4 levels in patients with ST-segment elevation myocardial infarction (STEMI) and its association with one-year major adverse cardiovascular events (MACE): A prospective cohort study.

In the present prospective cohort research, we aimed to explore the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in patients with ST-segment elevation myocardial infarction (STEMI) and its association with 1-year major adverse cardiovascular events (MACE). This prospective cohort study recruited 507 patients who underwent percutaneous coronary intervention for the treatment of STEMI at our hospital during August 2019 to July 2022. The serum ACSL4, tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and C-reactive protein levels were measured by enzyme-linked immunosorbent assay. Demographic and clinical statistics were also collected. In addition, all patients were followed up for 1 year, and patients with MACE were defined as poor prognosis group. All data used SPSS 26.0 to statistical analyses. The poor prognosis group had significantly higher age and low-density leptin cholesterol (LDLC) levels compared to the favorable prognosis group (P < .05). STEMI patients exhibited significantly elevated serum levels of ACSL4, tumor necrosis factor-α, IL-6, IL-1ß, and C-reactive protein (P < .05). Serum ACSL4 and IL-1ß levels in the poor prognosis group were remarkably enhanced compared to the favorable prognosis group. Curvilinear regression analysis demonstrated that ACSL4 was associated with LDLC and IL-1ß. Moreover, ACSL4 (B = 0.138, 95% CI 1.108-1.189, P < .001), LDLC (B = 2.317, 95% CI 5.253-19.603, P < .001), and IL-1ß (B = 0.061, 95%CI 1.008-1.122, P = .025) levels were the risk factors for STEMI patients with 1-year MACE. This study showed that the serum ACSL4 levels was remarkably elevated in STEMI patients. This study might provide new targets and a comprehensive approach to cardiovascular protection in STEMI patients.

Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes.

Importance: The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury. Objective: To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury. Design, Setting, and Participants: This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023. Exposures: In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE). Main Outcomes and Measures: The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event. Results: Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-year mortality: AUC, 0.785 vs 0.778; NRI, 0.078) in the derivation cohort. These findings were confirmed in the validation cohort. In the pooled population of 9450 patients, modified GRACE risk score showed superior performance compared with the original GRACE risk score in terms of reclassification and discrimination for in-hospital mortality end point (AUC, 0.878 vs 0.780; NRI, 0.097), 30-day mortality end point (AUC, 0.858 vs 0.771; NRI, 0.08), and 1-year mortality end point (AUC, 0.813 vs 0.797; NRI, 0.056). Conclusions and Relevance: In this study, using continuous rather than binary hs-cTn T at presentation, a proxy of the extent of myocardial injury, in the GRACE risk score improved the mortality risk prediction in patients with ACS.

Circulating miRNAs are associated with frailty and ST-elevation myocardial infarction pathways.

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.

Relationship between the Fibrinogen/Albumin Ratio and Microvascular Perfusion in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction: A Prospective Study. / Relação entre a Relação Fibrinogênio/Albumina e a Perfusão Microvascular em Pacientes Submetidos à Intervenção Coronária Percutânea Primária para Infarto do Miocárdio com Elevação do Segmento ST: Um Estudo Prospectivo.

BACKGROUND: Correct TIMI frame count (CTFC), myocardial blush grade (MBG), and ST-segment resolution (STR) are parameters used to evaluate reperfusion at the microvascular level in patients that have undergone primary percutaneous coronary intervention (pPCI). Fibrinogen-to-albumin ratio (FAR) has been associated with thrombotic events in patients with ST-elevation myocardial infarction (STEMI) and chronic venous insufficiency. OBJECTIVES: To investigate the relationship of FAR with CTFC, MBG, and STR. Methods: The study included 167 consecutive patients who underwent successful pPCI for STEMI and achieved TIMI-3 flow. The cases were divided into two groups, high (>0.0765) and low FAR (≤0.0765), according to the cut-off value of this parameter in the receiver operator characteristic analysis (ROC). STR, CTFC, and MBG were used to evaluate myocardial reperfusion. P values<0.05 were considered statistically significant. RESULTS: CTFC value, SYNTAX score, neutrophil/lymphocyte ratio, low-density lipoprotein, glucose, and peak cTnT were significantly higher, whereas STR, MBG, and LVEF were lower in the high FAR group. Spearman's correlation analysis revealed a significant relationship between the FAR and STR (r=-0.666, p<0.001), MBG (-0.523, p<0.001), and CTFC (r=0.731, p≤0.001). According to the logistic regression analysis, FAR, glucose, peak cTnT, and pain to balloon time were the most important independent predictors of MBG 0/1, CTFC>28, and STR<50%).ROC analysis revealed that the cut-off value of FAR≥0.0765 was a predictor of incomplete STR with a sensitivity of 71.9 % and a specificity of 69.8 %, MBG0/1 with a sensitivity of 72.6 % and a specificity of 68.6 %, and CTFC >28 with a sensitivity of 76 % and a specificity of 65.8 %. CONCLUSIONS: FAR is an important independent predictor of microvascular perfusion in patients undergoing pPCI for STEMI.

FUNDAMENTO: A contagem corrigida de quadros TIMI (CTFC), o grau de blush miocárdico (MBG) e a resolução do segmento ST (STR) são parâmetros utilizados para avaliar a reperfusão em nível microvascular em pacientes submetidos à intervenção coronária percutânea primária (ICPp). A relação fibrinogênio/albumina (FAR) tem sido associada a eventos trombóticos em pacientes com infarto do miocárdio com elevação do segmento ST (IAMCSST) e insuficiência venosa crônica. OBJETIVOS: Investigar a relação do FAR com CTFC, MBG e STR.Métodos: O estudo incluiu 167 pacientes consecutivos que foram submetidos a ICPp com sucesso para IAMCSST e alcançaram fluxo TIMI-3. Os casos foram divididos em dois grupos, FAR alto (> 0,0765) e FAR baixo (≤ 0,0765), de acordo com o valor de corte desse parâmetro na análise característica do operador do receptor (ROC).  STR, CTFC e MBG foram utilizados para avaliar a reperfusão miocárdica. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: O valor CTFC, escore SYNTAX, relação neutrófilos/linfócitos, lipoproteína de baixa densidade, glicose e pico de cTnT foram significativamente maiores, enquanto STR, MBG e FEVE foram menores no grupo FAR alto. A análise de correlação de Spearman revelou relação significativa entre FAR e STR (r=-0,666, p<0,001), MBG (-0,523, p<0,001) e CTFC (r=0,731, p≤0,001). De acordo com a análise de regressão logística, FAR, glicose, pico de cTnT e dor até o tempo de Balão foram os preditores independentes mais importantes de MBG 0/1, CTFC>28 e STR<50%). A análise ROC revelou que o ponto de corte o valor de FAR≥0,0765 foi preditor de STR incompleto com sensibilidade de 71,9% e especificidade de 69,8%, MBG0/1 com sensibilidade de 72,6% e especificidade de 68,6%, e CTFC>28 com sensibilidade de 76% e uma especificidade de 65,8%. CONCLUSÕES: A FAR é um importante preditor independente de perfusão microvascular em pacientes submetidos a ICPp por IAMCSST.

Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial.

BACKGROUND: We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. METHODS: In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). FINDINGS: (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. INTERPRETATION: Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. FUNDING: South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

Índice leucoglucémico en pacientes con infarto miocárdico con elevación del ST / Leuko-glycemic index in patients with ST elevation myocardial infarction

Introducción: la mortalidad asociada a infarto del miocardio (IM) no solo se debe a complicaciones cardiovasculares, sino también a complicaciones intrahospitalarias no cardiovasculares (CIHNC). El índice leuco-glucémico (ILG) se ha utilizado como un marcador pronóstico para el desarrollo de complicaciones cardiovasculares en el IM. Centramos este estudio en identificar el punto de corte de ILG para el desarrollo de CIHNC en pacientes con infarto de miocardio con elevación del segmento ST (IAMCEST). Material y métodos: en este diseño de un solo centro y transversal, incluimos pacientes con IAMCEST. El análisis bioquímico incluyó glucosa y leucocitos; se calculó ILG. Se realizaron análisis univariados y bivariados, curva ROC y análisis multivariado para el desarrollo de IAMCEST. Resultados: incluimos 1294 pacientes, 79.8% hombres y 20.2% mujeres. Las principales comorbilidades fueron: hipertensión arterial sistémica, diabetes mellitus y dislipidemia. Seiscientos cuarenta y cuatro pacientes (49.8%) presentaron CIHNC. El ILG > 1200 con área bajo la curva (AUC) 0.817 predice el desarrollo de CIHNC en pacientes con IAMCEST. Las variables que aumentaron el desarrollo de CIHNC fueron: ILG > 1200, creatinina > 0.91 mg/dL, diabetes mellitus y edad > 65 años. La neumonía intrahospitalaria y las complicaciones cardiovasculares aumentaron el riesgo de muerte entre los pacientes con IAMCEST. Conclusión: un LGI > 1200 aumentó más de nueve veces el riesgo de desarrollo de CIHNC en pacientes con IAMCEST.

Background: The myocardial infarction-associated (MI) mortality is not only due cardiovascular complications, but intrahospital non-cardiovascular complications (IHnCVCs). The leuko-glycemic index (LGI) has been used as a prognostic marker for the development of cardiovascular complications in MI. We focused this study on identifying the cut-off point of LGI for the IHnCVCs development in patients with ST-segment elevation myocardial infarction (STEMI).Material and methods: In this single-center and cross-sectional design, we included patients with STEMI. The biochemical analysis included glucose and leucocytes; with them we calculated the LGI. Receiver operating characteristic curve, univariate and bivariate analysis, and multivariate analysis for IHnCVCs development were performed. A p < 0.05 was considered statistically significant. Results: We included 1294 patients, 79.8% were men and 20.2% women. The main comorbidities were hypertension, diabetes mellitus and dyslipidemia. Six hundred forty-four (49.8%) patients presented IHNCVCs. The LGI > 1200 (AUC 0.817) predict the IHNCVCs development in STEMI patients. The variables that increased the IHNCVCs development were LGI > 1200, creatinine > 0.91 mg/dL, diabetes mellitus and age > 65 years. Hospital acquired pneumonia and cardiovascular complications increase the risk of death among STEMI patients. Conclusion: A LGI > 1200 increased, just over nine times, the risk of IHnCVC development in STEMI patients.

Diagnostic performance and predictive value of D-dimer testing in patients referred to the emergency department for suspected myocardial infarction.

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.

The gut hormone glucose-dependent insulinotropic polypeptide is downregulated in response to myocardial injury.

BACKGROUND: The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its metabolic function GIP has been found to exhibit direct cardio- and atheroprotective effects in mice and to be associated with cardiovascular prognosis in patients with myocardial infarction. The aim of this study was to characterize endogenous GIP levels in patients with acute myocardial infarction. METHODS AND RESULTS: Serum concentrations of GIP were assessed in 731 patients who presented with clinical indication of coronary angiography. Circulating GIP levels were significantly lower in patients with STEMI (ST-elevation myocardial infarction; n=100) compared to clinically stable patients without myocardial infarction (n=631) (216.82 pg/mL [Q1-Q3: 52.37-443.07] vs. 271.54 pg/mL [Q1-Q3: 70.12-542.41], p = 0.0266). To characterize endogenous GIP levels in patients with acute myocardial injury we enrolled 18 patients scheduled for cardiac surgery with cardiopulmonary bypass and requirement of extracorporeal circulation as a reproducible condition of myocardial injury. Blood samples were drawn directly before surgery (baseline), upon arrival at the intensive care unit (ICU), 6 h post arrival to the ICU and at the morning of the first and second postoperative days. Mean circulating GIP concentrations decreased in response to surgery from 45.3 ± 22.6 pg/mL at baseline to a minimum of 31.9 ± 19.8 pg/mL at the first postoperative day (p = 0.0384) and rose again at the second postoperative day (52.1 ± 28.0 pg/mL). CONCLUSIONS: Circulating GIP levels are downregulated in patients with myocardial infarction and following cardiac surgery. These results might suggest nutrition-independent regulation of GIP secretion following myocardial injury in humans.

Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction. / Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST.

BACKGROUND: Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. OBJECTIVES: The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). METHODS: One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. RESULTS: During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. CONCLUSIONS: Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

FUNDAMENTO: A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. OBJETIVOS: O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). MÉTODOS: Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. RESULTADOS: Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. CONCLUSÕES: A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

A New Score for Determining Thrombus Burden in STEMI Patients: The MAPH Score.

AIM: to investigate whether the MAPH score, which is a new score that combines blood viscosity biomarkers such as mean platelet volume (MPV), total protein and hematocrit, can be used to predict thrombus burden in ST-segment elevation myocardial infarction (STEMI) patients. METHODS: A total of 473 consecutive patients with STEMI were included in the study. Intracoronary tirofiban/abciximab infusion was applied to patients with thrombus load ≥3 and these patients (n = 71) were defined as the patient group with high thrombus load. MPV, age, hematocrit and total protein values of the patients were recorded. High shear rate (HSR) and low shear rate (LSR) were calculated from total protein and hematocrit values. Cut-off values were determined for high thrombus load by using Youden index, and score was determined as 0 or 1 according to cut-offs. The sum of the scores was calculated as the MAPH score. RESULTS: The mean age of the patients included in the study was 59.6 ± 12.6 (n = 354 male, 74.8%). There was no difference between the groups in terms of gender, HT and DM (P = .127, P = .402 and P = .576, respectively). In the group with high thrombus load; total protein, MPV and hematocrit values were higher (P < .001, P = .001 and P = .03, respectively). Comparison of receiver operating characteristic (ROC) curve analysis revealed that the MAPH score had better performance in predicting higher thrombus load than both other self-containing parameters and HSR and LSR. CONCLUSION: The MAPH score may be a new score that can be used to determine thrombus burden in STEMI patients.

Human Plasma Metabolomics Identify 9-cis-retinoic Acid and Dehydrophytosphingosine Levels as Novel biomarkers for Early Ventricular Fibrillation after ST-elevated Myocardial Infarction.

The relevant metabolite biomarkers for risk prediction of early onset of ventricular fibrillation (VF) after ST-segment elevation myocardial infarction (STEMI) remain unstudied. Here, we aimed to identify these imetabolites and the important metabolic pathways involved, and explore whether these metabolites could be used as predictors for the phenotype. Plasma samples were obtained retrospectively from a propensity-score matched cohort including 42 STEMI patients (21 consecutive VF and 21 non-VF). Ultra-performance liquid chromatography and mass spectrometry in combination with a comprehensive analysis of metabolomic data using Metaboanalyst 5.0 version were performed. As a result, the retinal metabolism pathway proved to be the most discriminative for the VF phenotype. Furthermore, 9-cis-Retinoic acid (9cRA) and dehydrophytosphingosine proved to be the most discriminative biomarkers. Biomarker analysis through receiver operating characteristic (ROC) curve showed the 2-metabolite biomarker panel yielding an area under the curve (AUC) of 0.836. The model based on Monte Carlo cross-validation found that 9cRA had the greatest probability of appearing in the predictive panel of biomarkers in the model. Validation of model efficiency based on an ROC curve showed that the combination model constructed by 9cRA and dehydrophytosphingosine had a good predictive value for early-onset VF after STEMI, and the AUC was 0.884 (95% CI 0.714-1). Conclusively, the retinol metabolism pathway was the most powerful pathway for differentiating the post-STEMI VF phenotype. 9cRA was the most important predictive biomarker of VF, and a plasma biomarker panel made up of two metabolites, may help to build a potent predictive model for VF.

Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST / Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction

Resumo Fundamento A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. Objetivos O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). Métodos Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. Resultados Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. Conclusões A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Abstract Background Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. Objectives The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). Methods One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. Results During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. Conclusions Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

Could serum ACE2 levels predict infarct size in acute phase of ST-segment elevation myocardial infarction: a comparative study with classical biomarkers.

OBJECTIVE: Serum ACE2 level in the acute phase of ST-segment elevation myocardial infarction may be an indicator of heart failure, however, limited studies have reported conflicting results. Therefore, in our study, we aimed to evaluate the relationship between serum ACE2 level and infarct size in the acute phase of ST-segment elevation myocardial infarction and compare the predictive value of ACE2 level with classical biomarkers. PATIENTS AND METHODS: Sixty-six patients after the primary percutaneous coronary intervention were included in the study. For the measurement of serum ACE2 levels, blood samples were taken twice from the patients: in the first 24 hours and on the 5th day of the infarction, and once from 30 healthy volunteers. hs-cTnT, BNP, and CRP levels were measured daily, and their peak values were taken. On the 7th day of ST-segment elevation myocardial infarction, gSPECT was used with the 99mTc-MIBI method for assessment of infarct size. RESULTS: Baseline ACE2 values were found to be higher in patients compared to controls, and ACE2 values obtained on the 5th day were found to be higher than the baseline values in the patients. There was no significant correlation between serum ACE2 levels and the RSS (%), while peak levels of hs-cTnT, BNP, and CRP were assessed as predictive factors for the RSS (%). CONCLUSIONS: Although serum ACE2 levels increased in the acute phase of ST-segment elevation myocardial infarction, this increase was not associated with infarct size. Serum ACE2 level did not provide additional benefit to classical biomarkers for infarct size-related prognosis prediction.

Elevated uric acid is related to the no-/slow-reflow phenomenon in STEMI undergoing primary PCI.

BACKGROUND: No-/slow-reflow phenomenon (NRP) is a severe complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This study aimed to explore the relationship between elevated serum uric acid (SUA) and NRP in patients with STEMI undergoing pPCI, focusing on inflammation and angiographic findings. METHODS: A total of 610 patients who received pPCI for STEMI were retrospectively enrolled. Patients were divided into a hyperuricaemia group and a non-hyperuricaemia group according to SUA levels. Clinical information and angiographic indicators were compared between the two groups. Thrombolysis in myocardial infarction (TIMI) flow and TIMI myocardial perfusion grade (TMPG) <3 after stent implantation were defined as TIMI-NRP and TMPG-NRP, respectively. A logistic model was used to analyse the relationship between hyperuricaemia and NRP. RESULTS: The hyperuricaemia group had a higher incidence of TIMI-NRP (24.9% vs 14.0%, p < .001) and TMPG-NRP (33.0% vs 24.9%, p = .03), higher levels of C-reactive protein (7.2 vs 4.1 mg/L, p < .001) and worse left ventricular ejection fraction (51.5% vs 54.0%, p = .002) than the non-hyperuricaemia group. As for angiographic findings, there was no significant difference between the two groups in terms of lesion characteristics measured by quantitative coronary angiography. After multivariable adjustment, elevated SUA was significantly associated with TIMI-NRP (odds ratio: 1.94, 95% confidence interval: 1.24-3.01, p = .003). Subgroup analysis showed that the effect of hyperuricaemia in TIMI-NRP was more pronounced in patients with delayed perfusion as well as in patients with diabetes mellitus. CONCLUSIONS: Elevated SUA is associated with severe inflammation and has higher incidence of TIMI-NRP in patients with STEMI undergoing pPCI, especially in those with delayed perfusion or diabetes mellitus.

Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity.

OBJECTIVE: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome during MI and identify corresponding functional consequences. Approach and Results: Platelets from patients experiencing ST-segment-elevation MI (STEMI) before and 3 days after treatment (n=30) and matched patients with severe stable coronary artery disease before and 3 days after coronary artery bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations in the proteins S100A8 and S100A9 were detected at the time of STEMI compared with stable coronary artery disease (S100A8: FC, 2.00; false discovery rate, 0.05; S100A9: FC, 2.28; false discovery rate, 0.005). During STEMI, only S100A8 mRNA and protein levels were correlated in platelets (R=0.46, P=0.012). To determine whether de novo protein synthesis occurs, activated platelets were incubated with 13C-labeled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was confidently detected. Platelet S100A8 and S100A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were coincubated under quiescent and activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Neutrophils released S100A8/A9 as free heterodimer, rather than in vesicles or extracellular traps. In the community-based Bruneck study (n=338), plasma S100A8/A9 was inversely associated with platelet reactivity-an effect abrogated by aspirin. CONCLUSIONS: Leukocyte-to-platelet protein transfer may occur in a thromboinflammatory environment such as STEMI. Plasma S100A8/A9 was negatively associated with platelet reactivity. These findings highlight neutrophils as potential modifiers for thrombotic therapies in coronary artery disease.

Association between serum hemoglobin and major cardiovascular adverse event in Chinese patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is a common clinical acute and severe disease, and it is of great significance to evaluate the prognosis of these patients. Hemoglobin levels are associated with a variety of diseases, but studies on Chinese patients with STEMI after percutaneous coronary intervention (PCI) have not been sufficient. METHODS: This was a secondary analysis based on a prospective cohort study of patients undergoing PCI in Taizhou, Zhejiang, China. We performed multivariable logistic regression to explore the association between the serum hemoglobin and the incidence of major cardiovascular adverse event (MACE) in patients after PCI. We also used a generalized additive model and smooth curve fitting to explain the nonlinear relationship after adjusting the potential confounders. Finally, the heterogeneity among specific groups was examined by subgroup analysis. RESULTS: Of all 462 patients enrolled in this study, 118 (25.54%) developed MACE. There was a negative correlation between serum hemoglobin and MACE in all three models (hazard ratio [HR] 0.82, 95% confidence interval [CI 0.72, 0.93], HR 0.86, 95% CI [0.76,0.98], and HR 0.87, 95% CI [0.74,0.98], respectively). In the subgroup analysis, the negative correlation existed between the patients who had myocardial infarction (MI) history (p for interaction = 0.0059) after adjusting covariates. However, no significant differences were found between age and sex groups (p for interaction = 0.1381, 0.4103, respectively). CONCLUSION: Our results indicated that patients who received PCI with low preoperative hemoglobin were more likely to develop MACE, especially if they have already had a history of MI.

Not-high before-treatment platelet reactivity in patients with STEMI: prevalence, clinical characteristics, response to therapy and outcomes.

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI.We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4-6 hours and 8-12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR.Overall, 20% patients had NHPR. Age and male gender both resulted independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point. However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; p = .017) as compared with the NHPR group.In conclusion, a significant proportion of patients presenting with STEMI has a baseline NHPR that is associated with better in-hospital outcomes as compared with patients with HPR. Further studies are needed to better elucidate the potential therapeutic implications of NHPR in terms of secondary prevention.

The relationship between serum rheumatoid factor level and SYNTAX score I in patients with acute myocardial infarction.

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.