Background: Myocardial injury is a known predictor of adverse outcomes. However, the impact of sex on its presentation, management, and prognosis is not fully understood. The aim of this study was to examine these differences in a tertiary hospital setting. Methods: We conducted a retrospective observational study of consecutive emergency department patients undergoing troponin testing from January 2012 to December 2013. Myocardial injury was classified as type 1 myocardial infarction (T1MI), type 2 myocardial infarction, or non-ischemic myocardial injury (NIMI). Clinical characteristics, management, and short- and long-term outcomes were compared by sex over a median follow-up of four years. Interaction analyses were performed to assess whether the effect of myocardial injury on outcomes differed between men and women. Results: Among 3620 patients, myocardial injury was more prevalent in men (31.4% vs. 25.8%; p < 0.001), with male sex independently associated with myocardial injury (odds ratio 1.32; 95% CI 1.11-1.58; p = 0.002). Risk factor profiles and electrocardiographic findings differed between sexes. NIMI was more common in women, while T1MI predominated in men (p < 0.001). Women with myocardial injury were less frequently hospitalized than men (63.1% vs. 74.3%, p < 0.001). After multivariable adjustment, long-term mortality was slightly higher in men (HR 3.39; 95% CI 2.73-4.21; p < 0.001), whereas women had higher adjusted risks of myocardial infarction (MI) (HR 4.11; 95% CI 2.35-7.17; p < 0.001) and heart failure (HF) (HR 1.78; 95% CI 1.25-2.55; p = 0.002). No significant interaction between sex and myocardial injury was observed for any outcome. Conclusions: Significant sex differences exist in myocardial injury type and prognosis. Women face increased risk of future MI and HF, whereas men have higher mortality risk. The effect of myocardial injury on long-term outcomes appears similar in both sexes.

Introduction and objectives: Only about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values < 55 mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. Methods: An independent, prospective, pragmatic, controlled, randomized, open-label, evaluator- blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin + bempedoic acid (BA) 180 mg + ezetimibe (EZ) 10 mg versus current European-based guidelines (high-potency statin f EZ 10 mg), in AMI patients. LDL-C will be determined within the first 48 hours. Patients with LDL-C > 115 mg/dL (without previous statin therapy), > 100 mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or > 70 mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72 hours post-AMI to the BA/EZ combination or to statin f EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C < 55 mg/dL at 8 weeks after treatment. Results: The results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. Conclusions: Early intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). Identification number: EudraCT 2021-006550-31. C 2024 Sociedad Espanola de Cardiolog & imath;a. Published by Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cancer and cardiovascular diseases are the leading causes of mortality worldwide, as they share common risk factors and exacerbate cardiovascular outcomes when they coexist. This study aimed to assess the clinical characteristics and cardiovascular outcomes of patients with a history of cancer and myocardial injury (MI) presenting with suspected acute coronary syndrome (ACS) in an emergency setting. This retrospective cohort study included 3,626 patients admitted to the emergency department with suspected ACS between 2012 and 2013. Patients were categorized on the basis of their cancer history and the presence of MI. Clinical variables and the associations between cancer history and MI with all-cause mortality were analyzed over a four-year follow-up period via univariate and multivariate Cox regression models. Of the cohort, 10.6

IntroductionCardiac troponin levels below the 99th percentile improve the predictive efficacy for cardiovascular events when associated with relevant clinical variables. However, whether ultra-sensitive analytical methods improve this predictive efficacy over less sensitive or contemporary analytical methods remains unknown.MethodsThis retrospective observational study involved consecutive patients who presented to the emergency department for suspected acute coronary syndrome and underwent measurement of ultra-sensitive cardiac troponin I (Singulex) and contemporary cardiac troponin I (Siemens) with levels below the 99th percentile. The clinical characteristics of these patients were analysed, and the efficacy of both analytical methods for predicting cardiovascular events over a 4-year follow-up period was compared.ResultsIn total, 838 patients were analysed (mean age, 62.9 ± 16.6 years; 42.2% women). Their cumulative incidence of the composite cardiovascular event (death, readmission for myocardial infarction, and readmission for heart failure) was 25.9% over the 4-year follow-up. Both Singulex cardiac troponin I (analysed by quartiles) and Siemens cardiac troponin (analysed as detectable/undetectable) improved the predictive efficacy for the combined event over clinical variables [Harrell's C-index (95% confidence interval): 0.77 (0.74–0.80) vs. 0.79 (0.76–0.81) and 0.77 (0.74–0.80) vs. 0.78 (0.75–0.81), respectively; p = 0.018]. However, there were no statistically significant difference between the two predictive models that included the aforementioned troponin assays.ConclusionsDetectable levels of cardiac troponin using a contemporary analytical method or those near the 99th percentile using an ultra-sensitive analytical method improve the predictive efficacy for cardiovascular events, with no differences between the two methods

BACKGROUND:This research examines the role of systematic cardiac troponin evaluation in identifying type 1 myocardial infarction among patients presenting to the emergency department with collected blood samples. METHODS:This was a prospective study of consecutive adult patients presenting to the emergency department of a university hospital between October 22, 2020, and January 11, 2021. Cardiac troponin I levels were measured in all patients, including those with suspected acute coronary syndrome (clinical testing) and a control group undergoing routine blood tests (non-clinical testing). The primary outcomes were the prevalence of type 1 myocardial infarction and the positive predictive value of cardiac troponin I, which were assessed using established statistical methods. RESULTS:Elevated cardiac troponin levels were identified in 13.4% of the study population (382/2,853). This included 19.5% of patients with clinically guided tests and 10.1% of those with non-clinical testing. The overall prevalence of type 1 myocardial infarction was 2%, with a positive predictive value of 14.9% (95% CI: 13.6-16.2). Among clinically guided tests, type 1 myocardial infarction prevalence was 5.8%, yielding a positive predictive value of 29.5% (95% CI: 26.7-32.4). Cases from non-clinically guided tests were primarily attributed to type 2 myocardial infarction or non-ischemic myocardial injury. CONCLUSION:Using a generalized approach to cardiac troponin testing in emergency department patients significantly lowers the diagnostic accuracy for type 1 myocardial infarction, reducing the positive predictive value and frequently indicating non-ischemic myocardial injury.

INTRODUCTION:Growth Differentiation Factor-15 (GDF-15) has been proven useful as a prognostic biomarker after an acute myocardial infarction (MI) and might be used to refine the selection of high-risk patients that could benefit from empagliflozin therapy. This study aims to compare the prognostic performance of GDF-15 with the inclusion criteria of the EMPACT-MI trial to identify patients at high risk of developing heart failure (HF) after an acute MI. METHODS AND RESULTS:A cohort of 275 acute MI patients with GDF-15 concentration available and long-term follow-up was analyzed. Patients were classified into two categories, high risk (HRHF) or no high risk of development of HF (NHRHF), according to two models: 1) GDF-15: HRHF if >1800 ng/L and NHRHF if ≤1800 ng/L; and 2) EMPACT-MI criteria: HRHF if meeting the trial inclusion criteria. Cox regression and ROC curve analyses were used to evaluate the prognostic performance of both models. GDF-15 showed a stronger association with the composite endpoint of all-cause death or first hospitalization for HF (HR 10.7, 95 % CI 5.5-21.0) compared to EMPACT-MI inclusion criteria (HR 3.9, 95 % CI 2.2-6.8). Additionally, GDF-15 had superior discriminative ability (c-index 0.790 vs 0.629, p = 0.004). Similar results were obtained for HF first hospitalization. CONCLUSIONS:GDF-15 may have a better discriminative ability than the inclusion criteria of the EMPACT-MI trial to identify those patients at higher risk of death and HF after an acute MI, who could potentially benefit from empagliflozin therapy.

The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12–1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Introduction and objectives: The optimal timing of coronary angiography in patients admitted with non-ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24 hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. Methods: This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. Results: Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67 +/- 12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score > 140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). Conclusions: In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low.

Objetivo. Evaluar las diferencias en el manejo clínico y eventos intrahospitalarios en una cohorte de pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) en función del sexo. Métodos. Estudio observacional, prospectivo y multicéntrico que incluyó pacientes consecutivos con diagnóstico de SCASEST sometidos a coronariografía con enfermedad ateroesclerótica responsable. Resultados. Entre abril y mayo de 2022 se incluyeron 1.020 pacientes; de ellos, 240 eran mujeres (23,5%). En comparación con los hombres, las mujeres fueron mayores (72,6 años vs 66,5 años; p < 0,001) y más frágiles (17,1% vs 5,6%; p < 0,001). No hubo diferencias en el pretratamiento con un inhibidor del receptor P2Y12 (68,8% vs 70,2%, p = 0,67), aunque las mujeres recibieron más pretratamiento con clopidogrel (56% vs 44%, p = 0,009), principalmente aquellas de edad < 75 años y sin fragilidad. En las mujeres se realizaron menos coronariografías precoces (# 24 h) (29,8% vs 36,9%; p = 0,03) a pesar de presentar la misma indicación (criterios de alto riesgo). En el análisis ajustado, la fragilidad, pero no el sexo, se asoció de forma independiente con la realización de una coronariografía diferida. La tasa y el tipo de revascularización fue igual en ambos sexos, y no hubo diferencias en los eventos cardiovasculares intrahospitalarios. Conclusiones. Las mujeres recibieron con mayor frecuencia un tratamiento antitrombótico menos potente. La fragilidad y no el sexo se asoció con la realización de coronariografía diferida. Sin embargo, no hubo diferencias en la tasa de revascularización coronaria ni en los eventos intrahospitalarios en función del sexo.

IntroductionThe prognostic ability of myocardial injury across different waves of the COVID-19 pandemic is not well established. The purpose of this study was to evaluate the prevalence and prognostic implications of myocardial injury in the first and sixth wave of COVID-19.MethodsWe conducted a retrospective observational study that included patients admitted to the emergency department with COVID-19 with data on concentrations of cardiac troponin during the first and sixth wave. We compared the prevalence of myocardial injury and its predictive capacity for 30-day all-cause death in both waves.Results and discussionA total of 346 patients were included (1st wave 199 and 6th wave 147 patients). The prevalence of myocardial injury was 21% with non-significant differences between waves. Myocardial injury was associated, in both waves, with a higher prevalence of comorbidities and with an increased risk of 30-day all-cause death [1st wave HR: 3.73 (1.84–7.55); p < 0.001 and 6th wave HR: 3.13 (1.23–7.92); p = 0.016], with non-significant differences in predictive capacity between groups after ROC curve analysis [AUC: 1st wave 0.829 (95% CI: 0.764–0.895) and 6th wave 0.794 (95% CI: 0.711–0.876)]. As limitations, this is a retrospective study with a relatively small simple size and troponin assay was performed at the discretion of the emergency physician so selection bias could be present. In conclusion, the prevalence of myocardial injury and its prognostic capacity was similar in both waves despite vaccination programs. Myocardial injury predicts short-term mortality in all COVID-19 patients, so they should be treated intensively.

BackgroundCardiovascular disease has traditionally been studied predominantly in men, but understanding its manifestations in women is crucial for effective management. This study aims to evaluate the long-term prognosis of female patients with acute coronary syndrome (ACS) within a tertiary hospital setting in Spain.MethodsRetrospective observational study based on a cohort of consecutive hospitalized patients with ACS from January 2009 to December 2014. Data on demographics, risk factors, treatment, and outcomes were collected, with a median follow-up of 9.2 years.ResultsWomen with ACS, constituting 27.3% of 2,330 patients, were older and had a higher prevalence of cardiovascular risk factors such as obesity, hypertension, and diabetes mellitus compared to men. They presented with more non-ST-segment elevation myocardial infarction and underwent less coronary angiography. Female patients were also less likely to be treated with acetylsalicylic acid, a second antiplatelet drug, or statins. Despite initial higher mortality rates [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.13–1.49; p < 0.001], female patients exhibited a more favorable long-term prognosis after adjustments (adjusted HR 0.82; 95% CI 0.71–0.96; p = 0.014), even in the subgroup analysis excluding patients with unstable angina.ConclusionsWomen with ACS are more comorbid, but after adjustments, female sex appears to be a protective factor that confers a better long-term prognosis.

Background: Effective risk communication is crucial for managing cardiovascular disease, the leading cause of global mortality. Clear communication between patients and physicians is essential for informed decision-making, yet gaps in understanding often persist. Objective: This study examines the state of risk communication during hospital admissions for cardiovascular events, evaluating both patient and physician perspectives and identifying factors influencing risk perception. Methods: The SEC-HARIPA study is a multicenter, cross-sectional analysis conducted across 28 Spanish centers from October 2022 to March 2023. It included 943 patients admitted to cardiology departments, either urgently or for scheduled procedures. Patients and their physicians completed parallel questionnaires assessing perceptions of cardiovascular risk, procedural complications, and overall communication. Statistical analysis focused on agreement between patient and physician perceptions and the impact of demographic and clinical variables. Results: The mean age of participants was 68.2 years, with ischemic heart disease being the most common cause of admission (41.3%). While 76.9% of patients felt adequately informed about procedural risks, 69.3% of those experiencing adverse events reported a lack of information on potential complications. A significant discrepancy was found between patients' and physicians' perceptions of future cardiovascular risk, with patients often underestimating their risk (weighted kappa index of 0.29). Key factors influencing risk perception included prior cardiovascular history, age, gender, and diabetes mellitus. Conclusions: This study reveals significant gaps in risk communication in cardiovascular care, particularly regarding future risks and complications. Tailoring communication strategies to individual patient characteristics could improve understanding and align perceptions with clinical realities, enhancing health outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement - The authors declare that they did not receive any payments or services from third parties for any part of the submitted work, including study design, manuscript preparation, or statistical analysis. - his study did not receive external funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research protocol received approval from the Ethics Committee of the Central University Hospital of the Defense "Gómez Ulla", as well as from the Ethics Committees of the participating hospitals, and adhered to the Helsinki Protocol. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data used in this study are available upon reasonable request, subject to [privacy restrictions, confidentiality agreements, etc.]. Interested parties can contact the corresponding author at juangorrizm@gmail.com and j\_o\_r\_d\_i_b@gmail.com to obtain access to the relevant data.

Introducción y objetivos: En la práctica habitual, solamente 1 de cada 3 pacientes con infarto agudo de miocardio (IAM) alcanza cifras de colesterol unido a lipoproteínas de baja densidad (cLDL) < 55 mg/dl en el primer año. El presente estudio pretende evaluar el impacto de un tratamiento intensivo precoz para el control lipídico tras un IAM.Métodos: Ensayo clínico independiente, prospectivo, pragmático, controlado, aleatorizado, abierto, ciego para el evaluador (diseño PROBE), que analiza la eficacia y la seguridad de un tratamiento hipolipemiante oral triple: estatina de alta potencia + ácido bempedoico [AB] 180 mg + ezetimiba [EZ] 10 mg frente a la estrategia basada en las vigentes recomendaciones (estatina de alta potencia ± EZ 10 mg) en pacientes con IAM. Se determina el cLDL en las primeras 48 h tras el IAM. Se aleatoriza 1:1 a AB+EZ o estatina ± EZ sin AB a los pacientes con cifras, entre las 24 y las 72 h tras el IAM, de cLDL ≥ 115 mg/dl sin estatinas previas, ≥ 100 mg/dl tras estatina de baja potencia o alta potencia a dosis no máxima o ≥ 70 mg/dl tras estatina de alta potencia a dosis máxima. El objetivo primario es el porcentaje de pacientes con cLDL < 55 mg/dl tras 8 semanas del tratamiento.Resultados: estos resultados aportarán información novedosa para el control del cLDL tras el IAM evaluando la utilidad de una estrategia hipolipemiante oral intensiva y precoz.Conclusiones: El tratamiento hipolipemiante oral triple precoz frente al tratamiento recomendado por las guías de práctica clínica podría facilitar la optimización del cLDL en los primeros 2 meses tras el IAM (periodo de alto riesgo).

RESUMEN Introducción y objetivos: El momento óptimo para la realización de un cateterismo diagnóstico en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) y la necesidad de pretratamiento con doble antiagregación son motivo de controversia. Este estudio pretende conocer el abordaje diagnóstico y terapéutico actual, así como la evolución clínica de los pacientes con SCASEST en España. Métodos: El estudio IMPACT of Time of Intervention in patients with Myocardial Infarction with Non-ST seGment elevation. ManaGement and Outcomes (IMPACT-TIMING-GO) es un registro nacional observacional, prospectivo y multicéntrico, que incluirá pacientes consecutivos con diagnóstico de SCASEST tratados con coronariografía diagnóstica y que presenten enfermedad coronaria aterosclerótica inestable o causal en 24 centros españoles. El objetivo primario del estudio es conocer el grado de cumplimiento de las recomendaciones de las guías de práctica clínica en pacientes que ingresan por SCASEST tratados con coronariografía en España, describir el uso del tratamiento antitrombótico antes del cateterismo y determinar el tiempo hasta este en la práctica clínica real. Se describirán también los eventos adversos cardiovasculares mayores: mortalidad por cualquier causa, infarto no fatal e ictus no fatal, y también la incidencia de hemorragia mayor según la escala BARC (Bleeding Academic Research Consortium) durante el seguimiento a 1 y 3 años. Resultados: Este registro permitirá mejorar el conocimiento en relación con el abordaje terapéutico inicial en pacientes que ingresan por SCASEST en España. Contribuirá a conocer sus características basales y su evolución clínica, así como el grado de adherencia y cumplimiento de las recomendaciones de las que se dispone actualmente. Conclusiones: Se trata del primer estudio prospectivo realizado en España que permitirá conocer las estrategias terapéuticas iniciales, tanto farmacológicas como intervencionistas, que se realizan en nuestro país en pacientes con SCASEST tras la publicación de las guías europeas de 2020, y la evolución clínica de estos pacientes a corto y largo plazo.

El momento óptimo para un cateterismo en el síndrome coronario agudo sin elevación del segmento ST (SCASEST) y la necesidad de pretratamiento son motivo de controversia. El objetivo principal del registro IMPACT-TIMING-GO es conocer el porcentaje de pacientes examinados con una coronariografía precoz (0-24 h) y que no recibieron doble antiagregación plaquetaria antes del cateterismo (estrategia sin pretratamiento) en España. Estudio observacional, prospectivo y multicéntrico, que incluyó a pacientes consecutivos con diagnóstico de SCASEST sometidos a cateterismo en los que se evidenció enfermedad coronaria ateroesclerótica causal. Entre abril y mayo de 2022 se incluyó a 1.021 pacientes (media de edad, 67 ± 12 años; el 23,6% mujeres). El 86,8% de los pacientes cumplían criterios de alto riesgo (elevación de troponina, cambios electrocardiográficos o puntuación GRACE > 140); sin embargo, únicamente el 37,8% se sometió a una estrategia invasiva precoz, y el 30,3% no recibió pretratamiento. Globalmente, solo el 13,6% de los pacientes se sometieron a una estrategia invasiva precoz sin un segundo antiagregante plaquetario, y la estrategia diferida con pretratamiento fue la más utilizada (46%). Durante el ingreso, 9 pacientes (0,9%) fallecieron y 34 (3,3%) presentaron una hemorragia grave. En España, solo el 13,6% de los pacientes con SCASEST sometidos a cateterismo reciben una estrategia invasiva precoz sin pretratamiento. La incidencia de eventos cardiovasculares y hemorragias graves en el ingreso es baja. The optimal timing of coronary angiography in patients admitted with non–ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24 hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67 ± 12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score > 140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low.

AimsTo examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations.MethodsThis is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR).ResultsAfter adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations.ConclusionThese findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications.

Introduction and objectives: The optimal time to perform a diagnostic coronary angiography in patients admitted due to non- ST-segment elevation acute coronary syndrome (NSTEACS) and start pretreatment with dual antiplatelet therapy is controversial. Our study aims to identify the current diagnostic and therapeutic approach, and clinical progression of patients with NSTEACS in our country. Methods: The IMPACT-TIMING-GO trial (Impact of time of intervention in patients with myocardial infarction with non-ST segment elevation. Management and outcomes) is a national, observational, prospective, and multicenter registry that will include consecutive patients from 24 Spanish centers with a clinical diagnosis of NSTEACS treated with diagnostic coronary angiography and with present unstable or causal atherosclerotic coronary artery disease. The study primary endpoint is to assess the level of compliance to clinical practice guidelines in patients admitted due to NSTEACS undergoing coronary angiography in Spain, describe the use of antithrombotic treatment prior to cardiac catheterization, and register the time elapsed until it is performed. Major adverse cardiovascular events will also be described like all-cause mortality, non-fatal myocardial infarction and non-fatal stroke, and the rate of major bleeding according to the BARC (Bleeding Academic Research Consortium) scale at 1- and 3-year follow-up. Results: This study will provide more information on the impact of different early management strategies in patients admitted with NSTEACS in Spain, and the degree of implementation of current recommendations into the routine clinical practice. It will also provide information on these patients' baseline and clinical characteristics. Conclusions: This is the first prospective study conducted in Spain that will be reporting on the early therapeutic strategies-both pharmacological and interventional-implemented in our country in patients with NSTEACS after the publication of the 2020 European guidelines, and on the clinical short- and long-term outcomes of these patients.

Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier’s Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case–control design. All of the included studies were of high quality according to the “Newcastle–Ottawa Scale”. TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.