Antitrombóticos: investigación y aplicaciones en la atención médica / Antithrombotics: Research and applications in healthcare

Resumen: Los antitrombóticos son fármacos que se utilizan para prevenir la formación de coágulos sanguíneos, también conocidos como trombos. Estos coágulos pueden causar graves problemas de salud, como infartos o enfermedades cerebrovasculares. En este artículo se analizan diferentes tipos de antitrombóticos, como los antiplaquetarios y los anticoagulantes, y se discuten sus mecanismos de acción. Además, se examinan los beneficios y los riesgos asociados con el uso de antitrombóticos. Por un lado, estos fármacos pueden reducir el riesgo de eventos trombóticos, lo que puede ser especialmente beneficioso en pacientes con condiciones de alto riesgo, como aquellos que han sufrido un infarto o que tienen fibrilación auricular. Por otro lado, también se discuten los posibles efectos secundarios de los antitrombóticos, como el aumento del riesgo de sangrado. Además, se proporcionan pautas para su uso seguro en diferentes escenarios clínicos. Finalmente, se abordan las estrategias de monitoreo y ajuste de la dosis de estos medicamentos para garantizar su eficacia y seguridad en los pacientes.

Abstract: Antithrombotics are drugs used to prevent the formation of blood clots, also known as thrombi. These clots can cause serious health problems, such as heart attacks or strokes. Different types of antithrombotics, such as antiplatelets and anticoagulants, are analyzed and their mechanisms of action are discussed. Additionally, the benefits and risks associated with the use of antithrombotics are examined. On the one hand, these drugs can reduce the risk of thrombotic events, which may be especially beneficial in patients with high-risk conditions, such as those who have suffered a heart attack or who have atrial fibrillation. On the other hand, the possible side effects of antithrombotics, such as the increased risk of bleeding, are also discussed and guidelines for their safe use in different clinical scenarios are provided. Additionally, monitoring and dose adjustment strategies for these medications are addressed to ensure their effectiveness and safety in patients.

Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

BACKGRUOUND: This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). METHODS: Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. RESULTS: During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). CONCLUSION: HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

[Effectiveness of the CNIC polypill in secondary cardiovascular prevention in the subgroup of patients of the NEPTUNO study using atorvastatin doses of 20 mg]. / Efectividad de la polipíldora CNIC en prevención cardiovascular secundaria en el subgrupo de pacientes del estudio NEPTUNO con dosis de atorvastatina de 20 mg.

Objective: To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients. Method: Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies. Results: 922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option. Conclusions: In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.

Objetivo: Analizar la incidencia y el riesgo de eventos adversos cardiovasculares mayores (MACE) recurrentes, el nivel de control de factores de riesgo, la persistencia al tratamiento y el coste de la versión de la polipíldora CNIC que contiene 100 mg de ácido acetilsalicílico (AAS), 20 mg de atorvastatina (A20) y 2.5/5.0 ó 10 mg de ramipril en pacientes en prevención cardiovascular secundaria. Método: Subanálisis del estudio observacional, retrospectivo y multicéntrico NEPTUNO en pacientes tratados durante 2 años con la polipíldora CNIC A20, los mismos monocomponentes por separado, medicamentos equipotentes uotras terapias. Resultados: Se incluyeron 922 pacientes en cada grupo. El riesgo de sufrir un MACE recurrente en el grupode polipíldora CNIC A20 fue menor que en todas las demás cohortes (21%, 23% y 26% de aumento del riesgo en las cohortesde monocomponentes, equipotentes u otras terapias, respectivamente; p < 0.05). La magnitud del cambio en el colesterol unidoa lipoproteínas de baja densidad y la presión arterial, así como el incremento en la proporción de pacientes que alcanzaron losobjetivos establecidos, fueron mayores en los pacientes tratados con la polipíldora CNIC A20 que en cualquiera de las otrascohortes (p < 0.001). La persistencia al tratamiento fue mayor en los pacientes tratados con la polipíldora CNIC A20 (p < 0.001)y esta estrategia resultó ser menos costosa que cualquier otra opción terapéutica. Conclusiones: En pacientes en prevencióncardiovascular secundaria, la polipíldora CNIC A20 (AAS 100 mg; atorvastatina 20 mg; ramipril 2.5/5.0 ó 10 mg) constituye unaopción terapéutica válida con beneficios y resultados similares a la versión de la polipíldora con 40 mg de atorvastatina.

Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia.

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects.Results:  LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05).Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.

[Box: see text].

Outcomes Associated with Giant Coronary Artery Aneurysms after Kawasaki Disease: A Single-Center United States Experience.

OBJECTIVES: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAAs) at a single US center. STUDY DESIGN: Medical records for all patients with KD and giant CAAs at a pediatric academic institution were reviewed. Primary outcomes included major adverse cardiovascular events (MACE) and normalization of CA luminal diameter, using Kaplan-Meier analyses. RESULTS: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with a median age at diagnosis of 0.9 years (range, 0.2-13.3 years). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 patients (21.7%) at a median of 1.4 years (range, 0.04-22.6 years) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z scores of ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to a normal luminal diameter at a median of 3.6 years (range, 0.6-12.0 years). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%. CONCLUSIONS: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z scores of ≥20. Despite regression to a normal luminal diameter in >25% of CAAs, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease.

[Correlation of left ventricular contractile function with the presence of collateral coronary circulation in non-reperfused acute myocardial infarction]. / Correlación de la función contráctil del ventrículo izquierdo con la presencia de circulación coronaria colateral en infarto agudo de miocardio no reperfundido.

Objective: To assess the association between coronary collateral circulation and ventricular contractile function in patients with non-reperfused acute myocardial infarction. Method: A retrospective and descriptive clinical study was conducted on patients with ST-elevation myocardial infarction (STEMI) at a reference cardiovascular center, from January 2006 to December 2022. Coronary angiographies and echocardiograms were reviewed to evaluate coronary collateral circulation and ventricular function, respectively. Patients were divided into groups based on the presence of collateral circulation. Both groups were compared and mortality during the index hospitalization was analyzed. Results: Out of a total of 14,985 patients with acute coronary syndrome, 8134 (54.3%) had the diagnosis of STEMI. We excluded 12,880, leaving a total of 2105 non-reperfused STEMI patients who underwent coronary angiography, revealing lesions. There were more patients without collateral circulation: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Patients without collateral circulation had a higher left ventricular ejection fraction (median of 47% vs. 42%; p < 0.001). Mortality in patients with collateral circulation was higher compared to those without it (11.6% vs. 9.8%; p = 0.225), but statistical significance was not reached. Conclusions: Non-reperfused STEMI patients did not show protection from collateral circulation when assessing left ventricular systolic function. We did not find a difference in mortality compared to the population without development of collateral circulation.

Objetivo: Evaluar la asociación entre la circulación coronaria colateral y la función contráctil ventricular en pacientes con infarto agudo de miocardio no reperfundido. Método: Estudio observacional descriptivo y retrospectivo en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en un centro cardiovascular de referencia, de enero de 2006 a diciembre de 2022. Se analizaron las coronariografías y los ecocardiogramas para evaluar la circulación coronaria colateral y la función ventricular, respectivamente. Se dividieron en grupos de acuerdo con la presencia de circulación colateral. Se compararon ambos grupos y se analizó la mortalidad durante la hospitalización del evento índice. Resultados: De 14,985 pacientes con síndrome coronario agudo, 8134 (54.3%) presentaron IAMCEST. Se excluyeron 12,880, quedando así 2105 pacientes con IAMCEST no reperfundidos y sometidos a coronariografía, revelando lesiones. Hubo más pacientes sin circulación colateral: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Los pacientes sin circulación colateral presentaron una mayor fracción de eyección ventricular izquierda (mediana del 47% vs. 42%; p < 0.001). La mortalidad en los pacientes con circulación colateral fue mayor que en los pacientes sin ella (11.6% vs. 9.8%; p = 0.225), pero no se alcanzó significancia estadística. Conclusiones: Los pacientes con IAMCEST no reperfundidos no presentaron protección por la circulación colateral al evaluar la función sistólica ventricular izquierda. No se encontró diferencia en la mortalidad en comparación con la población sin desarrollo de circulación colateral.

Is breakfast consumption detrimental, unnecessary, or an opportunity for health promotion? A review of cardiometabolic outcomes and functional food choices.

Breakfast consumption is generally considered a health-promoting habit for cardiometabolism, particularly with regard to chrononutrition. Glucose uptake is enhanced by proper insulin secretion triggered by the pancreatic clock, averting metabolic dysregulation related to insulin resistance. Breakfast skipping, in turn, is often considered a behaviour detrimental to health, in part due to putative inverse metabolic actions compared to breakfast consumption, such that breakfast skipping may promote circadian desynchrony. However, most ill health concerns about breakfast skipping are inferred from observational research, and recent well-controlled randomized clinical trials have shown benefits of breakfast skipping for cardiovascular risk factors. Accordingly, this review describes the effects of breakfast consumption versus breakfast skipping on cardiovascular risk factors (blood pressure and glycaemic and lipid indices). In addition, the view of breakfast consumption as an opportunity for functional food ingestion is considered to provide further insights into decision-making practice. Collectively, both breakfast consumption and breakfast skipping can be considered viable habits, but they depend on individual preferences, planning, and the specific foods being consumed or omitted. When consumed, breakfast should consist primarily of functional foods typical for this meal (e.g., eggs, dairy products, nuts, fruits, whole grains, coffee, tea, etc.). While breakfast consumption aligns with chrononutrition principles, breakfast skipping can contribute to a calorie deficit over time, which has the potential for widespread cardiometabolic benefits for patients with overweight/obesity. The concepts and practical considerations discussed in the present review may aid health care personnel in personalising breakfast consumption recommendations for diverse patient populations.

Myocardial perfusion scintigraphy in the assessment of cardiovascular risk in adult liver transplantation.

INTRODUCTION: The non-invasive diagnostic study of cardiovascular risk in patients who are going to undergo liver transplantation is not clear, especially in asymptomatic patients. Regarding myocardial perfusion scintigraphy (MPS), it has been thought that the impaired vasodilator reserve in these patients may reduce its performance. The objective is to assess the role of the MPS in the pre-surgical evaluation of patients who are going to undergo liver transplantation. MATERIAL AND METHODS: Retrospective, descriptive and observational study was designed. All adult patients undergoing liver transplantation between 2017 and 2021 who had previous MPS were included. The findings of MPS were described and correlated with the findings of invasive angiography and with the appearance or not of peri- and post-transplant cardiovascular events. RESULTS: There were a total of 188 transplanted patients (mean age: 57 years, SD: 12), 178 had previous myocardial perfusion, 82 (46%) patients had no cardiovascular risk factors, and 5 (2.8%) had a history of coronary disease. Of the MPS, 177 were with dipyridamole stress performed on average 10 months before transplantation. Only 17/178 (9.5%) studies were abnormal. The mean follow-up was 38 months (SD: 10). Of the patients with normal MPS, only 2 (1.2%) presented cardiovascular events, both with studies performed more than 2 years before the procedure. There were no deaths of cardiovascular origin. CONCLUSIONS: MPS is a safe and reliable technique for cardiovascular assessment of patients who are candidates for liver transplantation, given the low rate of false negatives during follow-up.

Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familialhypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131FH patients and 23 normolipidemic (NL) subjects. Results: LDLR, PCSK9 and LDLRP1 methylationwas similar between FH patients positive (MD) and negative (non-MD) for pathogenic variantsin FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups thanNL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated withclinical manifestations and cardiovascular events in FH patients (p < 0.05). Conclusion: Differentialmethylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascularevents. This methylation profile maybe useful as a biomarker and contribute to the management ofFH.

High-Sensitivity Troponin I and Cardiovascular Events in Stable Coronary Artery Disease: Insights from a Longitudinal Outpatient Study.

Numerous studies have been published suggesting that troponin levels are related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from unselected blood samples taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, an average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, and 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p = 0.017; 2.30 (1.37-3.88, p = 0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease who are adherent to treatment, troponin levels are independently associated with death and heart failure hospitalization in a medium-term follow-up.

Predictive values of bilirubin for in-hospital adverse events in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

PURPOSE: To investigate the association between serum bilirubin levels and in-hospital Major Adverse Cardiac Events (MACE) in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary Percutaneous Coronary Intervention (PCI). METHODS: A total of 418 patients with STEMI who underwent primary PCI were enrolled from October 1st, 2021 to October 31st 2022. The average age of enrolled participants was 59.23 years, and 328 patients (78.50%) were male patients. Patients were divided into MACE (patients with angina pectoris after infarction, recurrent myocardial infarction, acute heart failure, cardiogenic shock, malignant arrhythmias, or death after primary PCI) (n = 98) and non-MACE (n = 320) groups. Univariate and multivariate logistic regression analyses were performed to estimate the association between different bilirubin levels including Total Bilirubin (TB), Direct Bilirubin (DB), Indirect Bilirubin (IDB), and risk of in-hospital MACE. The area under the Receiver Operating Characteristic (ROC) curve was used to determine the accuracy of bilirubin levels in predicting in-hospital MACE. RESULTS: The incidence of MACE in STEMI patients increased from the lowest to the highest bilirubin tertiles. Multivariate logistic regression analysis showed that increased total bilirubin level was an independent predictor of in-hospital MACE in patients with STEMI (p for trend = 0.02). Compared to the first TB group, the ORs for risk of MACE were 1.58 (95% CI 0.77‒3.26) and 2.28 (95% CI 1.13‒4.59) in the second and third TB groups, respectively. The ROC curve analysis showed that the areas under the curve for TB, DB and IDB in predicting in-hospital MACE were 0.642 (95% CI 0.578‒0.705, p < 0.001), 0.676 (95% CI 0.614‒0.738, p < 0.001), and 0.619 (95% CI 0.554‒0.683, p < 0.001), respectively. CONCLUSIONS: The current study showed that elevated TB, DB, and IDB levels are independent predictors of in-hospital MACE in patients with STEMI after primary PCI, and that DB has a better predictive value than TB and IDB.

Effects of body weight variability on risks of macro- and microvascular outcomes in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort.

AIMS: To investigate the effects of body weight variability (BWV) on macro- and microvascular outcomes in a type 2 diabetes cohort. METHODS: BWV parameters were assessed in 684 individuals. Multivariable Cox regressions examined associations between BWV parameters and cardiovascular outcomes (total cardiovascular events [CVEs], major CVEs [MACEs], cardiovascular deaths),all-cause mortality and microvascular outcomes. Interaction/subgroup analyses were performed according to being physically-active/sedentary and having/not lost ≥ 5 % of weight. RESULTS: Median follow-up was 11 years over which 194 total CVEs (174 MACEs), and 223 all-cause deaths (110 cardiovascular), occurred. There were 215 renal, 152 retinopathy and 167 peripheral neuropathy development/worsening outcomes. In general, increased BWV was associated with higher risks of CVEs, MACEs, all-cause mortality, advanced renal failure and peripheral neuropathy outcomes, but not of microalbuminuria and retinopathy outcomes. On interaction/subgroup analyses, increased BWV was associated with higher risks of outcomes in sedentary individuals and in those who did not lose ≥ 5 % of body weight. In physically-active participants or in those who lost ≥ 5 % weight, the adjusted risks were null or protective. CONCLUSIONS: Increased BWV was associated with most adverse outcomes; however, in those who were physically-active or consistently losing weight, it was not hazardous and might be even beneficial.

Waist circumference cut-off points to identify major cardiovascular events and incident diabetes in Latin America: findings from the prospective Urban rural epidemiology study Colombia.

Background: Abdominal obesity (AO) indirectly represents visceral adiposity and can be assessed by waist circumference (WC) measurement. In Latin America, cut-off points for the diagnosis of AO are based on Asian population data. We aim to establish the WC cut-off points to predict major cardiovascular events (MACE) and incident diabetes. Methods: We analyzed data from the cohort PURE study in Colombia. WC cut-off points were defined according to the maximum Youden index. Multivariate logistic regression was used to obtain associations between WC and MACE, diabetes, and cumulative incidence of outcomes visualized using Kaplan-Meier curves. Results: After a mean follow-up of 12 years, 6,580 individuals with a mean age of 50.7 ± 9.7 years were included; 64.2% were women, and 53.5% were from rural areas. The mean WC was 85.2 ± 11.6 cm and 88.3 ± 11.1 cm in women and men, respectively. There were 635 cases of the MACE composite plus incident diabetes (5.25 events per 1,000 person-years). Using a cut-off value of 88.85 cm in men (sensitivity = 0.565) and 85.65 cm in women (sensitivity = 0.558) resulted in the highest value for the prediction of the main outcome. These values were associated with a 1.76 and 1.41-fold increased risk of presenting the composite outcome in men and women, respectively. Conclusions: We defined WC cut-off points of 89 cm in men and 86 cm in women to identify the elevated risk of MACE and incident diabetes. Therefore, we suggest using these values in cardiovascular risk assessment in Latin America.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Benefits of the Polypill on Medication Adherence in the Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review.

Background: Higher medication adherence reduces the risk of new cardiovascular events. However, there are individual and health system barriers that lead to lower adherence. The polypill has demonstrated benefits in cardiovascular morbidity and mortality mainly driven by an increase in adherence. We aim to evaluate the impact of the polypill on adherence to cardiovascular medication, its efficacy and safety in cardiovascular disease (CVD) prevention. Methods: A systematic review following PRISMA guidelines was conducted. Databases were searched from January 2003 to December 2022. We included randomized, pragmatic, or real-world clinical trials and observational studies. The primary outcome was medication adherence, secondary outcomes were efficacy in cardiovascular disease in primary and secondary prevention and safety. Results: From the 490 publications screened, 13 met the inclusion criteria and were incorporated into a comparative table Of those included, 70% were randomized controlled trials (RCTs) and 53.8% focused on secondary prevention. Most of the studies received a high and moderate quality rating. Self-report, pill counting and, the Morisky scale were the most frequent methods to evaluate adherence (84.6%). Compared with standard medication, the polypill improved overall medication adherence by 13%, with percentages ranging from 7.6% to 34.9%. Moreover, a potential benefit was also observed in reducing Major Adverse Cardiovascular Events (MACE), particularly in secondary prevention studies, with hazard ratios ranged between 0.43 to 0.76. Compared to standard care, the profile of side effects was similar. Conclusion: The polypill is an effective, safe, and practical strategy to improve adherence in people at risk of CVD. Although there is a demonstrated benefit in reducing MACE, predominantly in secondary prevention, there are still gaps in its efficacy in primary prevention and reducing total mortality. Therefore, the importance of obtaining long-term results of the polypill effect and how this strategy can be implemented in real practice.

Prognostic Impact of On-Treatment Cumulative Ambulatory Blood Pressures for Adverse Macro- and Microvascular Outcomes in Individuals With Type 2 Diabetes: The Rio de Janeiro Type 2 Diabetes Cohort.

BACKGROUND: The prognostic value of on-treatment mean cumulative ambulatory blood pressures (BPs) in type 2 diabetes has never been investigated. We aimed to assess it in a prospective cohort of 647 individuals with type 2 diabetes. METHODS: Clinic-office and ambulatory BPs were measured at baseline and serially during follow-up. Multivariable Cox analyses assessed the associations between baseline and mean cumulative BPs with the occurrence of cardiovascular events, major adverse cardiovascular events, all-cause and cardiovascular mortality, and microvascular outcomes (microalbuminuria, renal failure, retinopathy, and peripheral neuropathy). C statistics and the integrated discrimination improvement (IDI) index evaluated the improvement in risk discrimination by using cumulative ambulatory BPs instead of baseline BPs. RESULTS: Over a median follow-up of 10.6 years, there were 202 cardiovascular events (163 major adverse cardiovascular events), 254 all-cause deaths (118 cardiovascular); 125 individuals had microalbuminuria development/progression, 104 developed advanced renal failure, 159 had retinopathy, and 174 individuals had peripheral neuropathy development/progression. The risks associated with mean cumulative ambulatory BPs were in general higher than those associated with baseline BPs, particularly for cardiovascular (HR, 1.42 versus 1.25 for increments of 1 SD in 24-hour systolic blood pressure) and mortality outcomes (1.56 versus 1.26). Compared with cumulative clinic BPs, mean cumulative ambulatory BPs improved risk discrimination for most outcomes, with IDIs from 11% to 14% for major adverse cardiovascular events and mortality up to 24% to 26% for microalbuminuria and neuropathy. CONCLUSIONS: Compared with clinic-office BPs, mean cumulative ambulatory BPs during follow-up improve risk discrimination for most complications and mortality in individuals with type 2 diabetes. Serial ambulatory BP monitoring shall be more widely used in clinical management.

Benefits and harms of fibrate therapy in patients with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). METHODS: A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI). RESULTS: A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD -17.81, CI -33.92 to -1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events). CONCLUSIONS: Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms.

A recent experience on the role of influenza vaccination on cardiovascular events.

The purpose of this review is to update the recent information regarding the role of influenza vaccination (IV) as a strategy to reduce cardiovascular (CV) events. During the last 2 years, new meta-analysis, guidelines, and two randomized controlled trials (RCTs) were published. The IAMI trial added information regarding the safety and efficacy of IV right after an acute myocardial infarction hospitalization. A significant reduction in the primary endpoint-including mortality-was observed. More recently, the influenza vaccine to prevent vascular events trial (IVVE) trial did not meet the primary CV endpoint in patients with heart failure (HF). However, a significant reduction was observed during the seasonal peaks of Influenza circulation. COVID-19 pandemic provoked recruitment difficulties in these trials, as well as an altered influenza seasonality and incidence. Further analysis of IVVE trial is needed to clarify the precise role of IV in patients with HF. A recent meta-analysis of RCTs and observational studies indicated that IV was safe and effective to reduce CV events, and it was included in the most updated guideline. Despite these benefits, and the recommendations for its prescription by scientific societies and health regulatory agencies, the vaccination rate remains below than expected globally. The correct understanding of implementation barriers, which involve doctors, patients, and their context, is essential when continuous improvement strategies are planned, in order to improve the IV rate in at-risk subjects.

Prognostic importance of obstructive sleep apnea and CPAP treatment for cardiovascular and mortality outcomes in patients with resistant hypertension: a prospective cohort study.

The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events [CVEs] and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.

Prognostic importance of cardiovascular autonomic neuropathy on cardiovascular and mortality outcomes in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort.

AIMS: To investigate whether tests for cardiovascular autonomic neuropathy (CAN) and 24-hour heart rate variability (HRV) could improve the prediction for outcomes in type 2 diabetes. METHODS: 541 type 2 diabetic individuals performed tests of CAN. A subsample (313) had 24-hour HRV (the standard deviation of all normal RR intervals [SDNN] and the standard deviation of the averaged normal RR intervals for all 5 min segments [SDANN]). Multivariate Cox regressions examined the associations between CAN/low HRV with cardiovascular events (CVEs) and all-cause mortality. The improvement in risk discrimination of adding CAN/HRV was tested by C-statistics and by the Integrated Discrimination Improvement (IDI) index. RESULTS: 25% had CAN, and 17-18% had low HRV, respectively by SDANN-SDNN. Over a median follow-up of 12 years, there were 177 CVEs and 236 all-cause deaths in the whole cohort, and 96 CVEs and 129 all-cause deaths in the subsample. CAN was associated with 40% excess risks of CVEs/all-cause mortality, low HRV was associated with 2-fold higher risks of outcomes. HRV improved risk discrimination for CVEs/mortality with increases in C-statistics up to 0.039 and IDIs up to 25%. CONCLUSIONS: Low HRV was a better predictor of outcomes than tests of CAN, and it improved risk discrimination.