Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

INTRODUCTION: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. AIM: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. METHODS: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). RESULTS: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. CONCLUSION: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

Age shock index as an early predictor of cardiovascular death in acute coronary syndrome patients.

BACKGROUND: The shock index (SI), reflecting heart rate (HR) to SBP ratio, is established for predicting adverse outcomes in acute coronary syndrome (ACS) patients. Exploring the age shock index (ASI), obtained by multiplying SI with age, could offer further insights into ACS prognosis. OBJECTIVES: Assess ASI's effectiveness in predicting in-hospital death in individuals with ACS. METHODS: This study encompassed patients with acute myocardial infarction, drawn from a national registry spanning October 2010 to January 2022. The optimal ASI threshold was established using receiver operating characteristic (ROC) curve analysis. The primary outcome was in-hospital mortality. RESULTS: A total of 27 312 patients were enrolled, exhibiting a mean age of 66 ±â€…13 years, with 72.3% being male and 47.5% having ST-elevation myocardial infarction. ROC analysis yielded an area under the curve (AUC) of 0.80, identifying the optimal ASI cutoff as 44. Multivariate regression analysis, adjusting for potential confounders, established ASI ≥ 44 as an independent predictor of in-hospital death [hazard ratio: 3.09, 95% confidence interval: 2.56-3.71, P  < 0.001]. Furthermore, ASI emerged as a notably superior predictor of in-hospital death compared to the SI (AUC ASI  = 0.80 vs. AUC SI  = 0.72, P  < 0.0001), though it did not outperform the Global Registry of Acute Coronary Events (GRACE) score (AUC ASI  = 0.80 vs. AUC GRACE  = 0.85, P  < 0.001) or thrombolysis in myocardial infarction (TIMI) risk index (AUC ASI  = 0.80 vs. AUC TIMI  = 0.84, P  < 0.001). CONCLUSION: The ASI offers an expedient mean to promptly identify ACS patients at elevated risk of in-hospital death. Its simplicity and effectiveness could render it a valuable tool for early risk stratification in this population.

Diseño de un nuevo indicador de mortalidad en el síndrome coronario agudo al ingreso en la Unidad de Cuidados Intensivos / Design of a new mortality indicator in acute coronary syndrome on admission to the Intensive Care Unit

Objetivo: Diseñar un indicador de mortalidad del síndrome coronario agudo (SCA) en el servicio de medicina intensiva (SMI). Diseño: Estudio descriptivo observacional multicéntrico. Participantes: Pacientes con SCA ingresados en SMI incluidos en el registro ARIAM- SEMICYUC entre enero del 2013 y abril del 2019. Intervenciones: Ninguna. Variables de interés principales: Las variables analizadas fueron demográficas, tiempo de acceso al sistema sanitario y estado clínico. Se analizó la terapia de revascularización, los fármacos y la mortalidad. Se realizó un análisis de regresión logística de COX y posteriormente se diseñó una red neuronal. Se elaboró una curva ROC para calcula la potencia del nuevo score. Finalmente, la utilidad clínica o relevancia del indicador ARIAM se evaluará mediante un gráfico de Fagan. Resultados: Se incluyó a 17.258 pacientes, con una mortalidad al alta del SMI del 3,5% (605). Las variables analizadas con significación estadística (p<0,001) fueron introducidas en el modelo predictivo supervisado, una red neuronal artificial. El nuevo indicador ARIAM mostro una media de 0,0257 (IC del 95%, 0,0245-0,0267) en los pacientes dados de alta de UCI y de 0,27085 (IC del 95%, 0,2533-0,2886) en los que fallecieron, p <0,001. El área ROC del modelo conseguido fue de 0,918 (IC del 95%, 0,907-0,930). En el test de Fagan se demostró que el indicador ARIAM muestra que la probabilidad de fallecimiento es del 19% (IC del 95%, 18-20%) cuando es positivo y del 0,9% (IC del 95%, 0,8-1,01%) cuando es negativo. Conclusiones: Es posible crear un nuevo indicador de mortalidad del SCA en el SMI que sea más exacto, reproducible y actualizable periódicamente. (AU)

Objective: To design a mortality indicator for acute coronary syndrome (ACS) in the intensive care unit (ICU). Design: Multicenter observational descriptive study. Participants: ACS patients admitted to SMI included in the ARIAM-SEMICYUC registry between January 2013 and April 2019. Interventions: None. Main variables of interest: Variables analyzed were demographic, time of access to the health system, and clinical condition. Revascularization therapy, drugs, and mortality were analyzed. A COX regression analysis was performed and subsequently a neural network was designed. An ROC curve was developed to calculate the power of the new score. Finally, the clinical utility or relevance of the ARIAM's indicator will be evaluated using a Fagan test. Results: 17,258 patients were included, with a 3.5% (605) mortality at discharge from the ICU. The variables analyzed with statistical significance (p<0.001) were entered into the supervised predictive model, an artificial neural network. The new ARIAM's indicator showed a mean of 0.0257 (95% CI: 0.0245–0.0267) in patients discharged from the ICU and 0.27085 (95% CI: 0.2533–0.2886) in those who died, p<0.001. The ROC area of the model achieved was 0.918 (95% CI: 0.907–0.930). The Fagan test showed that the ARIAM's Indicator shows that the probability of death is 19% (95% CI: 18%–20%) when it is positive and 0.9% (95% CI: 0.8%–1.01%) when it is negative. Conclusions: It is possible to create a new mortality indicator for ACS in the ICU that is more accurate, reproducible, and periodically updated. (AU)

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)

Valor pronóstico de las frecuencias cardiacas bajas en pacientes ingresados con infarto agudo de miocardio / Prognostic value of low heart rates in patients admitted with acute myocardial infarction

Introducción y objetivos: Las escalas de predicción de riesgo utilizadas en síndromes coronarios agudos (SCA) utilizan modelos incrementales para estimar mortalidad para frecuencias cardiacas (FCs)> 60 lpm. Sin embargo, estudios previos comunicaron una relación no lineal entre la FC y los eventos, lo que sugiere que la FC baja puede tener un papel pronóstico no reconocido. El objetivo fue valorar el impacto pronóstico de las FCs baja en el SCA, definida como frecuencia cardiaca de admisión <50 lpm. Métodos: El estudio analizó datos del registro AMIS Plus, una cohorte de pacientes hospitalizados con SCA entre 1999 y 2021. El criterio de valoración principal fue la mortalidad hospitalaria por todas las causas, mientras que el compuesto de mortalidad por todas las causas se estableció por eventos cardiacos/cerebrovasculares mayores como secundario. Se adoptó una metodología estadística multinivel para evaluar el papel pronóstico de la FC baja en el SCA. Resultados: Se incluyó a 51.001 pacientes. La estimación cruda mostró una distribución bimodal de las variables resultados primaria y secundaria a FCs bajas y altas. Se observó una relación no lineal entre FCs y mortalidad intrahospitalaria mediante análisis restringido de spline cúbico. Una FC entre 50-75 mostró menor mortalidad que FC <50 lpm (OR=0,67; IC95%, 0,47-0,99) solo tras el análisis primario multivariado, no confirmado tras análisis múltiples de sensibilidad. Tras la puntuación de propensión emparejada, se hizo evidente el desvanecimiento progresivo del papel pronóstico de la FC <50 lpm. Conclusiones: Las FCs baja al ingreso en SCA se asocian a una mayor tasa cruda de eventos adversos. No obstante, tras la corrección de las diferencias basales, no se confirmó el papel pronóstico de la FC baja, sino que representa más bien un marcador de morbilidad subyacente. Estos resultados pueden ser clínicamente relevantes para mejorar la precisión de las puntuaciones de riesgo en el SCA.(AU)

Introduction and objectives: The risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR <50 bpm. Methods: This study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS. Results: The study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR <50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR <50 bpm was evident. Conclusions: Low admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.(AU)

Extremely Low Activity of Serum Alanine Aminotransferase Is Associated with Long-Term Overall-Cause Mortality in the Elderly Patients Undergoing Percutaneous Coronary Intervention after Acute Coronary Syndrome.

Background and Objectives: Recent studies revealed that the extremely low activity of serum alanine aminotransferase (ALT) is associated with frailty and contributes to increased mortality after acute physical stress. We aimed to investigate whether the extremely low activity of serum ALT (<10 U/L) at the time of diagnosis can be used to predict overall-cause mortality in elderly patients that underwent percutaneous coronary intervention (PCI) after acute coronary syndrome (ACS) diagnosis. Materials and Methods: A retrospective medical record review was performed on 1597 patients diagnosed with ACS who underwent PCI at a single university hospital from February 2014 to March 2020. The associations between the extremely low activity of serum ALT and mortality were assessed using a stepwise Cox regression (forward: conditional). Results: A total of 210 elderly patients were analyzed in this study. The number of deaths was 64 (30.5%), the mean survival time was 25.0 ± 18.9 months, and the mean age was 76.9 ± 7.6 years. The mean door-to-PCI time was 74.0 ± 20.9 min. The results of stepwise Cox regression analysis showed that the extremely low activity of serum ALT (adjusted hazard ratio: 5.157, 95% confidence interval: 3.001-8.862, p < 0.001) was the independent risk factor for long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. Conclusions: The extremely low activity of serum ALT at ACS diagnosis is a significant risk factor for increased long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. It is noteworthy that a simple laboratory test at the time of diagnosis was found to be a significant risk factor for mortality.

Higher mortality in acute coronary syndrome patients without standard modifiable risk factors: Results from a global meta-analysis of 1,285,722 patients.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes, hyperlipidemia, hypertension, and smoking, are used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. METHODS: Embase, Medline and Pubmed were searched for studies comparing SMuRF-less and SMuRF patients with first presentation of ACS. We conducted single-arm analyses to determine the proportion of SMuRF-less patients in the ACS cohort, and compared the clinical presentation and outcomes of these patients. RESULTS: Of 1,285,722 patients from 15 studies, 11.56% were SMuRF-less. A total of 7.44% of non-ST-segment-elevation ACS patients and 12.87% of ST-segment-elevation myocardial infarction (STEMI) patients were SMuRF-less. The proportion of SMuRF-less patients presenting with STEMI (60.71%) tended to be higher than those with SMuRFs (49.21%). Despite lower body mass index and fewer comorbidities such as chronic kidney disease, peripheral arterial disease, stroke and heart failure, SMuRF-less patients had increased in-hospital mortality (RR:1.57, 95%CI:1.38 to 1.80) and cardiogenic shock (RR:1.39, 95%CI:1.18 to 1.65), but lower risk of heart failure (RR:0.91, 95%CI:0.83 to 0.99). On discharge, SMuRF-less patients were prescribed less statins (RR:0.93, 95%CI:0.91 to 0.95), beta-blockers (RR:0.94, 95%CI:0.92 to 0.96), P2Y12 inhibitors (RR: 0.98, 95%CI: 0.96 to 0.99), and angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker (RR:0.92, 95%CI:0.75 to 0.91). CONCLUSION: In this study level meta-analysis, SMuRF-less ACS patients demonstrate higher mortality compared with patients with at least one traditional atherosclerotic risk factor. Underuse of guideline-directed medical therapy amongst SMuRF-less patients is concerning. Unraveling novel risk factors amongst SMuRF-less individuals is the next important step. SUMMARY: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes mellitus, hyperlipidemia, hypertension, and smoking, are often used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Of 1,285,722 ACS patients, 11.56% were SMuRF-less. Despite lower body mass index and fewer comorbidities, SMuRF-less patients had increased in-hospital mortality and cardiogenic shock. However, despite worse outcomes, SMuRF-less patients were prescribed less guideline-directed medical therapies on discharge.

Las diferencias por sexo en la mortalidad tras un síndrome coronario agudo se incrementan en los países de menor riqueza y mayor desigualdad de ingresos / Sex differences in mortality after an acute coronary syndrome increase with lower country wealth and higher income inequality

Introducción y objetivos: Aunque se han comunicado varios factores asociados con las diferencias por sexo en el tratamiento y el pronóstico tras un síndrome coronario agudo (SCA), se sabe poco acerca de la influencia de factores socioeconómicos en las disparidades por sexo. Nuestro objetivo es evaluar el impacto de la riqueza nacional y la desigualdad de ingresos en las diferencias por sexo en la mortalidad tras un SCA. Métodos: Se evaluaron las diferencias entre varones y mujeres en la mortalidad a los 2 años del alta hospitalaria de 23.489 pacientes con SCA de los registros EPICOR y EPICOR Asia. Se utilizaron modelos de regresión de Cox ajustados para evaluar los terciles del producto interior bruto y de desigualdad de ingresos. Resultados: Las mujeres (24,3%) eran de más edad que los varones (65,5 frente a 59,4 años; p <0,001), tenían más comorbilidades, se las revascularizó con menos frecuencia (el 63,6 frente al 75,6%; p <0,001) y recibieron al alta menos tratamientos recomendados por las guías de práctica clínica. Comparadas con los varones, la mortalidad de las mujeres en el seguimiento fue mayor (el 6,4 frente al 4,9%; p <0,001). La asociación entre sexo y mortalidad cambió su dirección desde una hazard ratio (HR)=1,32 (IC95%, 1,17-1,49) en el análisis univariado a HR=0,76 (IC95%, 0,67-0,87) después de ajustar por variables de confusión. Estas diferencias fueron más evidentes a medida que la riqueza de los países se incrementaba (HRpaísesconbajonivelderiqueza=0,85; IC95%, 0,72-1,00; HRpaísesconnivelderiquezaintermedio=0,66; IC95%, 0,50-0,87; HRpaísesconelevadonivelderiqueza=0,60; IC95%, 0,40-0,90; pparatestdetendencia=0,115) y a medida que se equilibraba la desigualdad de ingresos (HRbajoíndicededesigualidad=0,54; IC95%, 0,36-0,81; HRíndicededesigualidadintermedio=0,66; IC95%, 0,50-0,88; HRaltoíndicededesigualidad=0,87; IC95%, 0,74-1,03; pparatestdetendencia=0,031) (AU)

Introduction and objectives: Although several factors associated with sex differences in the management and outcomes after acute coronary syndrome (ACS) have been reported, little is known about the influence of socioeconomic factors on sex disparities. Our aim was to evaluate the influence of country wealth and income inequality on national sex differences in mortality after ACS. Methods: Sex differences in 2-year postdischarge mortality were evaluated in 23 489 ACS patients from the EPICOR and EPICOR Asia registries. Adjusted Cox regression models by country-based terciles of gross national income per capita and income inequality were used. Results: Women (24.3%) were older than men (65.5 vs 59.4 years, P <.001), had more comorbidities, were less often revascularized (63.6% vs 75.6%, P <.001) and received fewer guideline recommended therapies at discharge. Compared with men, a higher percentage of women died during follow-up (6.4% vs 4.9%, P <.001). The association between sex and mortality changed direction from hazard ratio (HR) 1.32 (95%CI, 1.17-1.49) in the univariate assessment to HR 0.76 (95%CI, 0.67-0.87) after adjustment for confounders. These differences were more evident with increasing country wealth (HRlow-incomecountries = 0.85; 95%CI, 0.72-1.00; HRmid-incomecountries = 0.66; 95%CI, 0.50-0.87; HRhigh-incomecountries = 0.60; 95%CI, 0.40-0.90; trend test P = .115) and with decreasing income inequality (HRlow-inequalityindex = 0.54; 95%CI, 0.36-0.81; HRintermediate-inequalityindex = 0.66; 95%CI, 0.50-0.88; HRhigh-inequalityindex = 0.87; 95%CI, 0.74-1.03; trend test P = .031). Conclusions: Women with ACS living in high socioeconomic countries showed a lower postdischarge mortality risk compared with men. This risk was attenuated in countries with poorer socioeconomic background, where adjusted mortality rates were similar between women and men (AU)

Validation of the Grace Risk Score to Predict In-Hospital and 6-Month Post-Discharge Mortality in Patients with Acute Coronary Syndrome

Abstract Background The wide range of clinical presentations of acute coronary syndrome (ACS) makes it indispensible to use tools for risk stratification and for appropriate risks management; thus, the use of prognosis scores is recommended in the immediat clinical decision-making. Objective To validate the Global Registry of Acute Coronary Events (GRACE) score as a predictor of in-hospital and 6-month post-discharge mortality in a population diagnosed with ACS. Methods This is a prospective cohort study of consecutive patients diagnosed with ACS between May and December 2018. GRACE scores were calculated, as well as their predictive value for in-hospital and 6-month post-discharge mortality. The validity of the model was assessed by two techniques: discriminative power using the area under the receiver operating characteristic curve (AUC) and goodness-of-fit, using the Hosmer-Lemeshow (HL) test, at the 5% level of significance. Results A total of 160 patients were included, mean age 64 (±10.9) years; of which 60% were men. The risk model showed to have satisfactory ability to predict both in-hospital mortality, with an area under the curve (AUC) of 0.76 (95% confidence interval [CI], 0.57-0.95; p = 0.014), and 6-month post-discharge mortality, with AUC of 0.78 (95%CI, 0.62-0.94), p = 0.002. The HL test indicated good-fit for both models of the GRACE score. Conclusion In this study, the GRACE risk score for predicting mortality was appropriately validated in patients with ACS, with good discriminative power and goodness-of-fit. The results suggest that the GRACE score is appropriate for clinical use in our setting.

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.

Evaluation of the long-term prognostic ability of triglyceride-glucose index for elderly acute coronary syndrome patients: a cohort study.

BACKGROUND: With the advancement of the world population aging, more attention should be paid to the prognosis of elderly patients with acute coronary syndrome (ACS). Triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance (IR) and is closely related to traditional risk factors of cardiovascular disease (CVD). However, the effect of TyG index on the prognosis of long-term adverse events in elderly ACS patients has not been reported. This study evaluated the prognostic power of TyG index in predicting adverse events in elderly ACS patients. METHODS: In this study, 662 ACS patients > 80 years old who were hospitalized from January 2006 to December 2012 were enrolled consecutively and the general clinical data and baseline blood biochemical indicators were collected. The follow-up time after discharge was 40-120 months (median, 63 months; interquartile range, 51‒74 months). In addition, the following formula was used to calculate the TyG index: Ln [fasting TG (mg/dL) × FBG (mg/dL)/2], and patients were divided into three groups according to the tertile of the TyG index. RESULTS: The mean age of the subjects was 81.87 ± 2.14 years, the proportion of females was 28.10%, and the mean TyG index was 8.76 ± 0.72. The TyG index was closely associated with the traditional risk factors of CVD. In the fully-adjusted Cox regression model, the Hazard ratio (95% CI) of all-cause mortality (in tertile 3) was 1.64 (1.06, 2.54) and major adverse cardiac event (MACE) (in tertile 3) was 1.36 (1.05, 1.95) for each SD increase in the TyG index. The subgroup analyses also confirmed the significant association of the TyG index and long-term prognosis. CONCLUSION: The TyG index is an independent predictor of long-term all-cause mortality and MACE in elderly ACS patients.

Anemia or other comorbidities? using machine learning to reveal deeper insights into the drivers of acute coronary syndromes in hospital admitted patients.

Acute coronary syndromes (ACS) are a leading cause of deaths worldwide, yet the diagnosis and treatment of this group of diseases represent a significant challenge for clinicians. The epidemiology of ACS is extremely complex and the relationship between ACS and patient risk factors is typically non-linear and highly variable across patient lifespan. Here, we aim to uncover deeper insights into the factors that shape ACS outcomes in hospitals across four Arabian Gulf countries. Further, because anemia is one of the most observed comorbidities, we explored its role in the prognosis of most prevalent ACS in-hospital outcomes (mortality, heart failure, and bleeding) in the region. We used a robust multi-algorithm interpretable machine learning (ML) pipeline, and 20 relevant risk factors to fit predictive models to 4,044 patients presenting with ACS between 2012 and 2013. We found that in-hospital heart failure followed by anemia was the most important predictor of mortality. However, anemia was the first most important predictor for both in-hospital heart failure, and bleeding. For all in-hospital outcome, anemia had remarkably non-linear relationships with both ACS outcomes and patients' baseline characteristics. With minimal statistical assumptions, our ML models had reasonable predictive performance (AUCs > 0.75) and substantially outperformed commonly used statistical and risk stratification methods. Moreover, our pipeline was able to elucidate ACS risk of individual patients based on their unique risk factors. Fully interpretable ML approaches are rarely used in clinical settings, particularly in the Middle East, but have the potential to improve clinicians' prognostic efforts and guide policymakers in reducing the health and economic burdens of ACS worldwide.

Prognostic implication of serum glycated albumin for patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

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.

Association of fasting blood glucose to high-density lipoprotein cholesterol ratio with short-term outcomes in patients with acute coronary syndrome.

BACKGROUND: Biochemical markers are crucial for determining risk in coronary artery disease (CAD) patients; however, the relationship between fasting blood glucose to high-density lipoprotein cholesterol (FG/HDL-C) ratio and short-term outcomes in acute coronary syndrome (ACS) patients remains unknown. Therefore, we have investigated the relationship between the FG/HDL-C ratio and short-term outcomes in ACS patients. METHODS: We used data from a pragmatic, stepped-wedge, cluster-randomized clinical trial to perform a post hoc analysis. A total of 11,284 individuals with ACS were subdivided into quartiles according to their FG/HDL-C ratios. We used a multivariate logistic regression model, two-piecewise linear regression model, and generalized additive model (GAM) to evaluate the relationship between the FG/HDL-C ratio and short-term outcomes (major adverse cardiovascular events [MACEs] and cardiovascular [CV] death within 30 days). RESULTS: The FG/HDL-C ratio was remarkably linked to an enhanced risk of MACEs and CV death in individuals with ACS in the highest quartile (MACEs, odds ratio [OR]: 1.49; 95% confidence interval [CI], [1.11, 1.99]; P < 0.01; CV death, OR: 1.69; 95% CI, [1.01, 1.41]; P = 0.04). The GAM suggested that the relationship between the FG/HDL-C ratio and MACEs and CV death was non-linear. The two-piecewise linear regression model demonstrated that the threshold values were 3.02 and 3.00 for MACEs and CV death, respectively. CONCLUSIONS: A higher FG/HDL-C ratio is associated with a higher risk of MACEs and CV death in patients with ACS.

High Triglyceride-Glucose Index is Associated with Poor Cardiovascular Outcomes in Nondiabetic Patients with ACS with LDL-C below 1.8 mmol/L.

AIM: To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS: A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS: Compared with the TyG index ＜8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index ＜8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS: In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Preoperative clopidogrel and outcomes in patients with acute coronary syndrome undergoing coronary artery bypass surgery.

OBJECTIVE: The optimal preoperative antiplatelet strategy for patients with acute coronary syndrome (ACS) requiring surgical revascularization remains unclear because of competing risks of bleeding and ischemic events. We evaluated the effect of clopidogrel within 5 days before coronary artery bypass grafting (CABG) on outcomes in patients with ACS. METHODS: Consecutive patients with ACS who underwent isolated CABG at a single center were included in this retrospective study. The primary outcome was a composite of death, myocardial infarction, and stroke within 30 days after surgery. Secondary outcomes were CABG-related major bleeding and perioperative transfusion. Inverse probability weighting using propensity score was performed to evaluate the risk-adjusted effect of preoperative clopidogrel on outcomes. RESULTS: Of 5543 patients with ACS, 820 (14.8%) patients continued clopidogrel within 5 days before CABG. After adjustment for differences in baseline factors, clopidogrel use ≤5 days before CABG was associated with significantly increased odds of the primary composite outcome (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.29; P = .005), stroke (OR, 3.13; 95% CI, 1.82-5.39; P < .001), major bleeding (OR, 2.01; 95% CI, 1.56-2.58; P < .001), and transfusion (OR, 2.05; 95% CI, 1.82-2.30; P < .001). The effects of preoperative clopidogrel use ≤5 days on primary outcome and major bleeding were greater in patients older than 65 years. CONCLUSIONS: Among patients with ACS undergoing CABG, clopidogrel therapy within 5 days before surgery was associated with increased odds of major cardiac and cerebrovascular events and bleeding complications than discontinuing clopidogrel for >5 days.

Addressing Posttreatment Selection Bias in Comparative Effectiveness Research, Using Real-World Data and Simulation.

To examine methodologies that address imbalanced treatment switching and censoring, 6 different analytical approaches were evaluated under a comparative effectiveness framework: intention-to-treat, as-treated, intention-to-treat with censor-weighting, as-treated with censor-weighting, time-varying exposure, and time-varying exposure with censor-weighting. Marginal structural models were employed to address time-varying exposure, confounding, and possibly informative censoring in an administrative data set of adult patients who were hospitalized with acute coronary syndrome and treated with either clopidogrel or ticagrelor. The effectiveness endpoint included first occurrence of death, myocardial infarction, or stroke. These methodologies were then applied across simulated data sets with varying frequencies of treatment switching and censoring to compare the effect estimate of each analysis. The findings suggest that implementing different analytical approaches has an impact on the point estimate and interpretation of analyses, especially when censoring is highly unbalanced.

Prognostic value of circulating microRNAs compared to high-sensitivity troponin T in patients presenting with suspected acute coronary syndrome to the emergency department.

BACKGROUND: To evaluate the prognostic value of eleven microRNAs (miRNAs) compared to high-sensitivity Troponin T (hs-cTnT) in patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED). METHODS: 1,042 patients presenting between August 2014 and April 2017 were included. Expression levels of eleven microRNAs (miR-21-5p, miR-22-3p, miR-29a-3p, miR-92a-3p, miR-122-5p, miR-126-3p, miR-132-3p, miR-133a-3p, miR-134-5p, miR-191-3p, and miR-423-5p) were determined using RT-qPCR. All-cause mortality (ACM) and a composite of ACM, acute myocardial infarction (AMI) and stroke were defined as endpoints. RESULTS: During a median follow-up of 399 (P25-P75: 381-525) days 58 patients (5.6%) died. The composite endpoint occurred in 86 patients (8.3%). Different expression levels of miR-21-5p (median, P25-P75: 5.28 [5.14-5.51] vs. 5.16 [4.97-5.35], p = 0.0033) and miR-122-5p (median, P25-P75: 5.17 [4.81-5.49] vs. 5.35 [5.01-5.69], p = 0.0184) were observed in patients who died compared to survivors. ROC-optimized cutoff of miR-21-5p (HR, P25-P75: 3.3 [1.2-9.4], p = 0.0239), but not miR-122-5p (HR, P25-P75: 0.4 [0.2-0.8], p = 0.0116), was predictive for all-cause mortality, even after adjustment in a multivariate model. Nevertheless, addition of miR-21-5p and miR-122-5p decreased prognostic accuracy of hs-cTnT for all-cause mortality (△AUC: 0.112, p = 0.0159). Hs-cTnT admission values had a high prognostic value for ACM (AUC [95%CI] = 0.794 [0.751-0.837]) and the composite of ACM, AMI and stroke (AUC [95%CI] = 0.745 [0.695-0.794]). CONCLUSIONS: Despite a different expression depending on outcomes miR-21-5p and miR-122-5p do not add prognostic information to hs-cTnT in patients presenting with suspected ACS to the ED.