Is having a moderate or low history, electrocardiogram, age, risk factors, troponin risk score a handicap for long-term mortality?

OBJECTIVE: History, electrocardiogram, age, risk factors, troponin risk score and troponin level follow-up are used to safely discharge low-risk patients with suspected non-ST elevation acute coronary syndrome from the emergency department for a 1-month period. We aimed to comprehensively investigate the 6-month mortality of patients with the history, electrocardiogram, age, risk factors, troponin risk score. METHODS: A total of 949 non-ST elevation acute coronary syndrome patients admitted to the emergency department from 01.01.2019 to 01.10.2019 were included in this retrospective study. History, electrocardiogram, age, risk factors, troponin scores of all patients were calculated by two emergency clinicians and a cardiologist. We compared the 6-month mortality of the groups. RESULTS: The mean age of the patients was 67.9 (56.4-79) years; 57.3% were male and 42.7% were female. Six-month mortality was significantly lower in the high-risk history, electrocardiogram, age, risk factors, troponin score group than in the low- and moderate-risk groups: 11/80 (12.1%), 58/206 (22%), and 150/444 (25.3%), respectively (p=0.019). CONCLUSION: Patients with high history, electrocardiogram, age, risk factors, troponin risk scores are generally treated with coronary angioplasty as soon as possible. We found that the mortality rate of this group of patients was lower in the long term compared with others. Efforts are also needed to reduce the mortality of moderate and low-risk patients. Further studies are needed on the factors affecting the 6-month mortality of moderate and low-risk acute coronary syndrome patients.

Assessment of platelet functional activity in healthy individuals and patients receiving antiplatelet therapy. Possible inconsistencies between aggregation and flow cytometry tests.

Platelet functional activity was assessed in healthy volunteers (HV, n=92), patients with stable angina pectoris (SA, n=42) and acute coronary syndrome (ACS, n=73), treated with acetylsalicylic acid (ASA) + clopidogrel and ASA + ticagrelor, respectively. In all HV and patients we have compared parameters of platelet aggregation (maximum light transmission and velocity, Tmax and Vmax) and parameters, characterizing exposure of platelet activation markers, evaluated by flow cytometry. HV platelets were activated by 10 µM, 1 µM TRAP, and 20 µM, 5 µM, 2.5 µM ADP; patient platelets were activated by 10 µM TRAP and by 20 µM and 5 µM ADP. Strong and significant correlations between the aggregation and flow cytometry parameters (the r correlation coefficient from 0.4 up to >0.6) most frequently were registered in HV platelet during activation by 1 µM TRAP and in SA patients during platelet activation by 20 µM and 5 µM ADP. However, in many other cases these correlations were rather weak (r < 0.3) and sometimes statistically insignificant. In HV the differences in PAC-1 binding parameters between platelets activated by 10 µM TRAP (the strongest agonist) and all ADP concentrations were negligible (≤ 10%), while CD62P binding (at all ADP concentrations) and LTA parameters for (5 µM and 2.5 µM ADP) were significantly lower (by 40-60%). Antiplatelet therapy in patients decreased all parameters as compared to HV, but to varying extents. For 10 µM TRAP the MFI index for PAC-1 binding (40-50% decrease) and for both ADP concentrations the Tmax values (60-85% decrease) appeared to be the most sensitive in comparison with the other parameters that decreased to a lesser extent. The data obtained indicate a possibility of inconsistency between different LTA and flow cytometry parameters in assessing platelet activity and efficacy of antiplatelet drugs.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

Effects of the stress hyperglycemia ratio on long-term mortality in patients with triple-vessel disease and acute coronary syndrome.

AIMS: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). METHODS: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. RESULTS: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. CONCLUSIONS: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Preclinical identification of acute coronary syndrome without high sensitivity troponin assays using machine learning algorithms.

Preclinical management of patients with acute chest pain and their identification as candidates for urgent coronary revascularization without the use of high sensitivity troponin essays remains a critical challenge in emergency medicine. We enrolled 2760 patients (average age 70 years, 58.6% male) with chest pain and suspected ACS, who were admitted to the Emergency Department of the University Hospital Tübingen, Germany, between August 2016 and October 2020. Using 26 features, eight Machine learning models (non-deep learning models) were trained with data from the preclinical rescue protocol and compared to the "TropOut" score (a modified version of the "preHEART" score which consists of history, ECG, age and cardiac risk but without troponin analysis) to predict major adverse cardiac event (MACE) and acute coronary artery occlusion (ACAO). In our study population MACE occurred in 823 (29.8%) patients and ACAO occurred in 480 patients (17.4%). Interestingly, we found that all machine learning models outperformed the "TropOut" score. The VC and the LR models showed the highest area under the receiver operating characteristic (AUROC) for predicting MACE (AUROC = 0.78) and the VC showed the highest AUROC for predicting ACAO (AUROC = 0.81). A SHapley Additive exPlanations (SHAP) analyses based on the XGB model showed that presence of ST-elevations in the electrocardiogram (ECG) were the most important features to predict both endpoints.

Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients.

C1q/TNF-related protein 3 (CTRP3) represents an adipokine with various metabolic and immune-regulatory functions. While circulating CTRP3 has been proposed as a potential biomarker for cardiovascular disease (CVD), current data on CTRP3 regarding coronary artery disease (CAD) remains partially contradictory. This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). A total of 206 patients were classified into three groups: CCS (n = 64), ACS having a first acute event (ACS-1, n = 75), and ACS having a recurrent acute event (ACS-2, n = 67). The control group consisted of 49 healthy individuals. ELISA measurement in peripheral blood revealed decreased CTRP3 levels in all patient groups (p < 0.001) without significant differences between the groups. This effect was exclusively observed in male patients. Females generally exhibited significantly higher CTRP3 plasma levels than males. ROC curve analysis in male patients revealed a valuable predictive potency of plasma CTRP3 in order to identify CAD patients, with a proposed cut-off value of 51.25 ng/mL. The sensitivity and specificity of prediction by CTRP3 were congruent for the subgroups of CCS, ACS-1, and ACS-2 patients. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings, with male mice exhibiting higher circulating CTRP3 levels than females. We conclude that circulating CTRP3 levels are decreased in both male CCS and ACS patients. Therefore, CTRP3 might be useful as a biomarker for CAD but not for distinguishing an acute from a chronic setting. KEY MESSAGES: CTRP3 levels were found to be decreased in both male CCS and ACS patients compared to healthy controls. Plasma CTRP3 has a valuable predictive potency in order to identify CAD patients among men and is therefore proposed as a biomarker for CAD but not for distinguishing between acute and chronic settings. Regulation of circulating CTRP3 levels in murine models of cardiovascular pathophysiology was found to be partly opposite to the clinical findings in men.

Preinterventional pan-immune-inflammation value as a tool to predict postcontrast acute kidney injury among acute coronary syndrome patients implanted drug-eluting stents: a retrospective observational study.

We evaluated the value of pan-immune-inflammation value (PIV) in predicting the risk for postcontrast acute kidney injury (PCAKI), an important complication following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients. Medical records of 839 ACS patients underwent PCI between June 2019 and December 2022 were retrospectively analyzed. Patients were divided into two groups: PCAKI (-) and PCAKI (+). PCAKI was defined as a ≥ 0.5 mg/dL and/or a ≥ 25% increase in serum creatinine within 72 h after PCI. The PIV was computed as [neutrophils × platelets × monocytes]÷lymphocytes. The mean age was 60.7 ± 12.9 years. PCAKI was detected in 105 (12.51%) patients. PIV was higher in the PCAKI (+) group compared to PCAKI (-) group (median 1150, interquartile range [IQR] 663-2021 vs median 366, IQR 238-527, p < 0.001). Receiver operating characteristic curve analysis showed that the best cutoff of PIV for predicting PCAKI was 576 with 81% sensitivity and 80% specificity. PIV was superior to neutrophil-lymphocyte ratio and platelet-lymphocyte ratio for the prediction of PCAKI (area under curve:0.894, 0.849 and 0.817, respectively, p < 0.001 for all). A high PIV was independently correlated with PCAKI (≤576 vs. >576, odds ratio [OR] 12.484, 95%confidence interval [CI] 4.853-32.118, p < 0.001) together with older age (OR 1.058, p = 0.009), female gender (OR 4.374, p = 0.005), active smoking (OR 0.193, p = 0.012), left ventricular ejection fraction (OR 0.954, p = 0.021), creatinine (OR 10.120, p < 0.001), hemoglobin (OR 0.759, p = 0.019) and c-reactive protein (OR 1.121, p = 0.002). In conclusion, a high PIV seems to be an easily assessable tool that can be used in clinical practice for predicting the risk of PCAKI in ACS patients implanted drug-eluting stents.

To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline.

OBJECTIVES: To accurately evaluate non-ST-elevated acute cardiac syndrome (NSTE-ACS), the quality of high-sensitive cardiac troponin (hs-cTn) assays is of vital importance. The 2020 revision of the NSTE-ACS guideline includes clinical decision-limits (CDL's) to both rule-in and rule-out NSTE-ACS for most commercially available platforms, providing both 0/1 h and 0/2 h delta limits. Our study evaluated whether laboratories are able to meet the analytical performance specifications for imprecision (APS) for hs-cTnT. METHODS: Results from external quality assurance (EQA) in commutable samples were used to evaluate the current and historic performance of analyzers. The performance of analyzers that either passed or failed to comply with 0/1 h-APS were used on a real-world dataset of first hs-cTnT-values to simulate 10.000 samples of t=0, t=1 and t=2 h values with multiple delta's for all relevant CDL's. We compared the simulated values to the input values to obtain the percentage of aberrant results simulated. RESULTS: The majority of analyzers complies with APS for rule-in in 2022 (0/1 h: 90.4 % and 0/2 h: 100 %), compliance for the 0/1 h rule-out is still far from optimal (0/1 h: 30.7 %, 0/2 h: 75.4 %), with improving compliance over the past years (rule-in p=<0.0001, rule-out p=0.011, χ2). Whilst 0/1 h-APS-passing analyzers have a minute risk to falsely rule-out patients whom should be ruled-in (0.0001 %), failing performance increases this risk to 2.1 % upon using 0/1 h CDL's. Here, adopting 0/2 h CDL's is favorable (0.01 %). CONCLUSIONS: Laboratories that fail to meet hs-cTnT 0/1 h-APS should improve their performance to the required and achievable level. Until performance is reached clinics should adopt the 0/2 h CDL's.

Temporal biomarker concentration patterns during the early course of acute coronary syndrome.

OBJECTIVES: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. METHODS: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. RESULTS: The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. CONCLUSIONS: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.

Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study.

Acute coronary syndrome (ACS) includes myocardial infarction (MI) and unstable angina (UA). MI is defined by elevated necrosis markers, preferably high-sensitivity cardiac troponins (hs-cTn). However, it takes hours for cTn to become elevated after coronary occlusion; therefore, difficulties are associated with diagnosing early post-onset MI or UA. The aim of this prospective cohort study was to examine the diagnostic ability of serum nardilysin (NRDC) for the early detection of ACS. This study consisted of two sequential cohorts, the Phase I cohort, 435 patients presenting to the emergency room (ER) with chest pain, and the Phase II cohort, 486 patients with chest pain who underwent coronary angiography. The final diagnosis was ACS in 155 out of 435 patients (35.6%) in the phase I and 418 out of 486 (86.0%) in the phase II cohort. Among 680 patients who presented within 24 h of onset, 466 patients (68.5%) were diagnosed with ACS. Serum NRDC levels were significantly higher in patients with ACS than in those without ACS. The sensitivity of NRDC in patients who presented within 6 h after the onset was higher than that of hsTnI, and the AUC of NRDC within 1 h of the onset was higher than that of hsTnI (0.718 versus 0.633). Among hsTnI-negative patients (300 of 680 patients: 44.1%), 136 of whom (45.3%) were diagnosed with ACS, the sensitivity and the NPV of NRDC were 73.5 and 65.7%, respectively. When measured in combination with hsTnI, NRDC plays auxiliary roles in the early diagnosis of ACS.

Troponin testing in routine primary care: observations from a dynamic cohort study in the Amsterdam metropolitan area.

OBJECTIVES: Troponin testing is indicated in the diagnostic work-up of acute coronary syndrome (ACS) and incorporated in risk stratification pathways. This study aims to gain insights on the use, outcomes, and diagnostic accuracy of troponin testing in routine primary care; a setting that is understudied. METHODS: Routine data were used from the academic primary care network in the Amsterdam metropolitan area (968,433 patient records). The study population included adult patients who underwent high-sensitivity troponin I or T (hs-TnI/T) testing between 2011 and 2021. The primary outcome was the reported diagnosis and the secondary outcome was the diagnostic accuracy measured by death or ACS at 30 days. RESULTS: 3,184 patients underwent hs-troponin testing, either with hsTNT (n=2,333) or hsTNI (n=851). Median patients' age was 55 (44-65) years, and 62.3 % were female. Predominant symptoms were chest pain and dyspnea (56.7 %). Additional diagnostic laboratory tests were commonly performed (CRP: 47.7 %, natriuretic peptides: 25.6 %, d-dimer: 21.5 %). Most common diagnoses were musculoskeletal symptoms (21.6 %) and coronary heart disease (7.1 %; 1.1 % ACS). Troponin testing showed sensitivity and specificity of 77.8 % (60.9-89.9) and 94.3 % (93.5-95.1), respectively. Negative and positive predictive values were 99.7 (99.5-99.9) and 13.5 (11.1-16.4), and positive and negative likelihood ratios were 13.7 (10.9-17.1) and 0.24 (0.13-0.43). CONCLUSIONS: GPs occasionally use troponin testing in very low-risk patients, often as part of a multi-marker rule-out strategy. The diagnostic characteristics of troponin tests, while promising, warrant prospective validation and implementation to facilitate appropriate use.

Lower Plasma miR-223 Level Is Associated with Clopidogrel Resistance in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the relationship between the plasma miR-223 expression level and clopidogrel resistance in acute coronary syndrome (ACS) patients. Methods: We performed a search for publications using online databases including PubMed, EMBASE, Cochrane Library, and Chinese Databases (CNKI database, Weipu database, and Wanfang database) from the inception of the databases to June 18, 2023, to identify studies reporting the relationship between the plasma miR-223 level and clopidogrel resistance in ACS patients. Two researchers independently searched and screened to ensure the consistency of the results and assess the quality of the included studies according to the Newcastle-Ottawa scale. A fixed-effects model was used for pooling data with STATA 14.0. Results: Four articles including 399 Chinese ACS patients were eligible for the meta-analysis. Low plasma miR-223 levels were independently correlated with clopidogrel resistance in Chinese ACS patients (OR 0.58, 95% CI: 0.33-1.04). Conclusion: Lower plasma miR-223 levels are associated with clopidogrel resistance in Chinese ACS patients, suggesting that miR-223 may be a potential diagnostic biomarker of clopidogrel resistance.

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.

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo / Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome

Introducción y objetivos: La fibrosis hepática precede a la cirrosis y a la insuficiencia hepática. Las formas subclínicas de fibrosis hepática podrían aumentar el riesgo de eventos cardiovasculares. El objetivo fue describir el valor pronóstico del índice FIB-4 en pacientes con síndrome coronario agudo (SCA) sobre la mortalidad hospitalaria y el pronóstico posterior. Métodos: Estudio retrospectivo de pacientes con SCA en un centro. Los objetivos de análisis fueron la mortalidad en la fase hospitalaria y tras el alta, así como la insuficiencia cardiaca y el sangrado mayor (SM), que se evaluaron tomando como evento competitivo la mortalidad por todas las causas y se presentan los sub-hazard ratios (sHR). Los eventos recurrentes se evaluaron mediante la razón de tasas de incidencia (IRR). Resultados: Se incluyeron a 3.106 pacientes y el 6,66% tenía un índice FIB-4 ≥ 1,3. El análisis multivariado verificó mayor riesgo de mortalidad intrahospitalaria asociado al índice FIB-4 (OR = 1,24; p=0,016) y los pacientes con valores> 2,67 presentaron el doble de riesgo (OR = 2,35; p=0,038). Tras el alta (mediana de seguimiento 1.112 días) el índice FIB-4 no tuvo valor pronóstico de mortalidad pero valores ≥ 1,3 se asociaron a mayor riesgo del primer reingreso (Shr = 1,61; p=0,04) o recurrente (IRR =1,70; p=0,001) de IC. El índice FIB-4 ≥ 1,30 se asoció con mayor riesgo de SM (sHR = 1,62; p=0,030). Conclusiones: La evaluación de la fibrosis hepática por el índice FIB-4 identifica a los pacientes con SCA con mayor riesgo de mortalidad intrahospitalaria pero también con mayor riesgo de IC y SM tras el alta.(AU)

Introduction and objectives: Liver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). Methods: Retrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). Results: We included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). Conclusions : The assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.(AU)

Retrospective Study of the Association Between Platelet-to-Lymphocyte Ratio in Patients with Acute Coronary Syndrome on Admission to a Rural Referral Center in East Java, Indonesia, and the Incidence of New Symptomatic Heart Failure at 6 Months.

BACKGROUND This was a retrospective study conducted at a rural referral center in East Java, Indonesia, to evaluate the association between the platelet-to-lymphocyte ratio (PLR) on hospital admission and the incidence of new symptomatic heart failure (HF) within 6 months in patients with acute coronary syndrome (ACS). MATERIAL AND METHODS The study population consisted of all ACS patients who were hospitalized between 1 January and 31 December 2018 at a non-percutaneous coronary intervention-capable secondary referral hospital and came for a routine follow-up until 6 months afterwards. The diagnosis of new symptomatic HF was based on International Classification of Diseases 10th revision code I50.9. RESULTS From 126 hospitalized patients, 92 patients were included in the analysis. The incidence rate of new symptomatic HF at 6 months was 70.65%. High PLR upon initial admission was significantly associated with new symptomatic HF incidence (odds ratio=1.70, P<0.001). PLR was also able to discriminate new symptomatic HF incidence at 6 months with area under the curve of 0.83 (P=0.001). Multivariate Cox regression analysis showed that PLR was an independent predictor for new symptomatic HF incidence (hazard ratio=4.5, P=0.001). CONCLUSIONS In a rural center in Indonesia, the PLR was independently correlated with the onset of new symptomatic HF in patients with ACS 6 months after hospital admission. The PLR may be a supplementary biomarker for clinical outcomes in patients with ACS for use in resource-limited regions.

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study.

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. CONCLUSIONS: These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. TRIAL REGISTRATION: ClinicalTrials.gov - NCT03507309.

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.

Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction.

BACKGROUND: Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). METHODS: A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs' apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. RESULTS: Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p < 0.01). There was no significant difference when comparing T2D with and without chronic CAD. The ratio of CD42-CD62 +/CD42-CD31 + EMPs was reduced in all T2D patients, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analyzed. It revealed a significant differential expression of 5 factors in patients with ACS and diabetes, including TGF-ß1, PD-ECGF, platelet factor 4, serpin E1, and thrombospondin 1. Ingenuity Pathway Analysis revealed that those five differentially expressed molecules, mainly TGF-ß1, inhibit key pathways involved in normal endothelial function. Further comparison of the three diabetes groups to healthy controls and diabetes without cardiovascular disease to diabetes with CAD identified networks that inhibit normal endothelial cell function. Interestingly, DDP-IV was the only differentially expressed protein between chronic CAD and ACS in patients with diabetes. CONCLUSION: Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.