[Fine-tuning of antithrombotic therapy in patients with non-valvular atrial fibrillation. The AFINVA register]. / Adecuación del tratamiento antitrombótico en los pacientes con fibrilación auricular no valvular. Registro AFINVA.

OBJECTIVE: To determine whether antithrombotic treatment (ATT) in patients with non-valvular atrial fibrillation in a health area complies with the recommendations of current clinical guidelines. DESIGN: Prospective observational study. LOCATION: Primary Health Care Centres and Cardiology Department of a Health Department of the Valencian Community, Spain. PARTICIPANTS: A total of 505 patients with nonvalvular atrial fibrillation were included in the study. MAIN MEASUREMENTS: ATT was deemed to be inappropriate in patients with a CHA2DS2-VASc score ≥1 and who were not under oral anticoagulation, in patients treated with antivitaminK drugs, and poor control of oral anticoagulation, or with antiplatelet therapy inappropriately associated with anticoagulation, and in patients on ATT with a CHA2DS2-VASc score=0. RESULTS: The median age was 77.4±10years. The ATT was considered inadequate in 58% of cases. Factors independently associated with inadequate ATT were age (OR: 1.02 [1-1.04]; P=.029), hypothyroidism (OR: 1.98 [1.14-3.43]; P=.015), ischaemic heart disease (OR: 1.3 [1.15-2.59]; P=.008) and paroxysmal non-valvular AF (OR: 2.11 [1.41-3.17]; P<.0001). CONCLUSIONS: These data underline the high prevalence of inadequate ATT in daily practice, as well its different causes.

Does Gender Influence the Indication of Treatment and Long-Term Prognosis in Severe Aortic Stenosis?

INTRODUCTION: It is a matter of controversy whether the therapeutic strategy for severe aortic stenosis (AS) differs according to gender. METHODS: Retrospective study of patients diagnosed with severe AS (transvalvular mean gradient ≥ 40 mmHg and/or aortic valvular area < 1 cm2) between 2009 and 2019. Our aim was to assess the association of sex on AVR or medical management and outcomes in patients with severe AS. RESULTS: 452 patients were included. Women (51.1%) were older than men (80 ± 8.4 vs. 75.8 ± 9.9 years; p < 0.001). Aortic valve replacement (AVR) was performed less frequently in women (43.4% vs. 53.2%; p = 0.03), but multivariate analyses showed that sex was not an independent predictor factor for AVR. Age, Charlson index and symptoms were predictive factors (OR 0.81 [0.82-0.89], OR 0.81 [0.71-0.93], OR 22.02 [6.77-71.64]). Survival analysis revealed no significant association of sex within all-cause and cardiovascular mortalities (log-rank p = 0.63 and p = 0.07). Cox proportional hazards analyses showed AVR (HR: 0.1 [0.06-0.15]), Charlson index (HR: 1.13 [1.06-1.21]) and reduced LVEF (HR: 1.9 [1.32-2.73]) to be independent cardiovascular mortality predictors. CONCLUSIONS: Gender is not associated with AVR or long-term prognosis. Cardiovascular mortality was associated with older age, more comorbidity and worse LVEF.

Association between Proinflammatory Markers, Leukocyte-Endothelium Interactions, and Carotid Intima-Media Thickness in Type 2 Diabetes: Role of Glycemic Control.

Glycated hemoglobin monitorization could be a tool for maintaining type 2 diabetes (T2D) under control and delaying the appearance of cardiovascular events. This cross-sectional study was designed to assess the role of glycemic control in modulating early-stage markers of cardiovascular complications. One hundred and eight healthy controls and 161 type 2 diabetic patients were recruited and distributed according to their glycemic control, setting the threshold at 6.5% (good control). Biochemical and anthropometrical parameters were registered during the initial visit, and peripheral blood was extracted to obtain polymorphonuclear cells and analyze inflammatory markers, adhesion molecules, leukocyte-endothelium interactions, and carotid intima-media thickness. Correlations between these parameters were explored. We found that inflammatory markers and adhesion molecules were augmented in type 2 diabetic subjects with poor glycemic control. Polymorphonuclear leukocytes interacted more with the endothelium in the diabetic population, and even more significantly in the poorly controlled subjects. In parallel, carotid intima-media thickness was also increased in the diabetic population, and the difference was greater among poorly controlled subjects. Finally, correlation measurement revealed that carotid intima-media thickness was related to glycemic control and lipid metabolism in diabetic patients. Our results suggest that glycemic control delays the onset of cardiovascular comorbidities in diabetic subjects.

Does Glycemic Control Modulate the Impairment of NLRP3 Inflammasome Activation in Type 2 Diabetes?

Since mitochondrial dysfunction is associated with NOD-like receptor family protein 3 (NLRP3) activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients [25 with glycated hemoglobin (HbA1c) ≤7% and 36 with HbA1c ≥8%] and 40 healthy controls. Total and mitochondrial reactive oxygen species (ROS) production was enhanced in T2D patients, and mitochondrial ROS was more pronounced in those with poor glycemic control. Levels of gene and protein expression of NLRP3 were decreased in both diabetic groups and more so in those with HbA1c ≥8%. In addition, there was a decrease in gene expression and serum concentrations of interleukin (IL)-1ß, IL-12, and caspase-1 in line with inhibition of the NLRP3 inflammasome. Our data also suggest negative correlations between HbA1c levels and NLRP3 protein expression, serum levels of IL-12 and IL-1ß, and caspase-1 messenger RNA expression. Our findings lead us to raise the hypothesis of an association between poor glycemic control in T2D and an impairment of the NLRP3 inflammasome, suggesting that glycemic control plays an important role in the immune response of diabetic subjects.

Long-term prognosis of chronic kidney disease in non-ST elevation acute coronary syndrome treated with invasive strategy. / Pronóstico a largo plazo de la enfermedad renal crónica en el síndrome coronario agudo sin elevación del segmento ST tratado con estrategia invasiva.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular outcomes after non-ST elevation acute coronary syndrome (NSTEACS). However, the information available on this specific population, is scarce. We evaluate the impact of CKD on long-term prognosis in patients with NSTEACS managed with invasive strategy. METHODS: We conduct a prospective registry of patients with NSTEACS and coronary angiography. CKD was defined as a glomerular filtration rate < 60ml/min/1,73m2. The composite primary end-point was cardiac death and non fatal cardiovascular readmission. We estimated the cumulative probability and hazard rate (HR) of combined primary end-point at 3-years according to the presence or absence of CKD. RESULTS: We included 248 p with mean age of 66.9 years, 25% women. CKD was present at baseline in 67 patients (27%). Patients with CKD were older (74.9 vs. 63.9 years; P<.0001) with more prevalence of hypertension (89.6 vs. 66.3%; P<.0001), diabetes (53.7 vs. 35.9%; P=.011), history of heart failure (13.4 vs. 3.9%; P=.006) and anemia (47.8 vs. 16%; P<.0001). No differences in the extent of coronary artery disease. CKD was associated with higher cumulative probability (49.3 vs. 28.2%; log-rank P=.001) and HR of the primary combined end-point (HR: 1.94; CI95%: 1.12-3.27; P=.012). CKD was an independent predictor of adverse cardiovascular outcomes at 3-years (HR: 1.66; CI95%: 1.05-2.61; P=.03). CONCLUSIONS: In NSTEACS patients treated with invasive strategie CKD is associated independently with an increased risk of adverse cardiovascular outcomes at 3years.

Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?

Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c] <6.5% and 43 with HbA1c >6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was reduced and fission was increased in diabetic patients, and both features were accentuated in patients with poor glycemic control. Furthermore, leukocyte rolling flux rose in parallel to HbA1c levels. The induction of leukocyte-endothelial interactions in diabetic patients was related to reduced mitochondrial fusion and higher mitochondrial fission. Our findings suggest that mitochondrial dynamics could be influenced by glycemic control in leukocytes of diabetic patients, in which there is decreased mitochondrial fusion and elevated fission related to enhanced leukocyte-endothelial interactions. These findings lead to the hypothesis that poor glycemic control during T2D may alter mitochondrial dynamics and could eventually promote leukocyte-endothelial interactions and the onset of cardiovascular diseases. Antioxid. Redox Signal. 25, 108-115.

[Prognostic value of troponin T in hospitalized patients with angina or non-ST-segment elevation myocardial infarction]. / Valor pronóstico de la tropinina T en pacientes hospitalizados con angina o infarto sin elevación del segmento ST.

INTRODUCTION AND OBJECTIVES: Cardiac troponins are highly specific and sensitive for detecting minimal myocardial damage. The aim of our study was to determine the prognostic value of troponin T levels in patients hospitalized for suspected angina or myocardial infarction without ST-segment elevation. PATIENTS AND METHOD: We recorded the frequency of death, acute myocardial infarction, heart failure, or need for coronary revascularization in the three months after the onset of symptoms in 346 consecutive patients admitted for suspected acute coronary syndrome, excluding those who developed myocardial infarction with persistent ST-segment elevation. RESULT: . Serum troponin T levels were > or = 0.1 ng/ml in 133 patients (troponin T positive group) and lower in 213 patients (troponin T negative group). The relative risk (RR) and 95 percent confidence intervals (95% CI) of individual and grouped events for the troponin T positive group were 3.2 (95% CI, 1.4-7.3; p = 0.006) for death; 2.8 (95% CI, 1.43-5.51; p = 0.003) for death or myocardial infarction; and 2.8 (95% CI, 1.6-5.0; p < 0.001) for death, myocardial infarction or heart failure. Diabetes mellitus and troponin T levels > or = 0.1 ng/ml had independent prognostic value after adjusting for age, sex, and electrocardiographic changes; with RR 2.5 (95% CI, 1.01-5.9) for death, myocardial infarction or heart failure. CONCLUSIONS: The prognosis of patients hospitalized for chest pain who do not immediately develop transmural necrosis depends on serum troponin T levels at hospital admission. Troponin T levels > or = 0.1 ng/ml almost triple the risk of major events in the three months after the acute episode. The prognostic value of troponin T is independent of age, sex, presence of diabetes mellitus, and electrocardiographic changes.

Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia.

OBJECTIVE: Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS: Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition- and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS: Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist. CONCLUSIONS: Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.

Utilidad marginal de la escala SAMe-TT 2 R 2 en la predicción de la calidad de la anticoagulación oral con acenocumarol en el "mundo real" / Marginal usefulness of the SAMe-TT 2 R 2 score in the prediction of the quality of oral anticoagulation with acenocoumarol in the "real world"

Resumen Introducción: la escala SAMe-TT2R2 ha sido propuesta para predecir la calidad de la anticoagulación con antagonistas de la vitamina K. Objetivo: validar la capacidad discriminativa de la escala SAMe-TT2R2 en una cohorte de pacientes con fibrilación auricular no valvular de la vida real. Métodos: estudio observacional de pacientes con fibrilación auricular no valvular tratados con antagonistas de la vitamina K al menos seis meses. Se consideró buen control de anticoagulación un tiempo en rango terapéutico ≥ 65% estimado con el método de Rosendaal. Se evaluó la asociación entre puntuación SAMe-TT2R2 y el control de anticoagulación con regresión logística binaria. La capacidad de discriminación se analizó mediante el cálculo del valor del área bajo la curva ROC. Resultados: se incluyeron 241 pacientes de edad media 78,6±8,6 años, 53% mujeres. La media del tiempo en rango terapéutico fue 59,4±25,4%, menor según aumentó la puntuación SAMe-TT2R2. En general, la escala no mostró capacidad para discriminar los pacientes con adecuado control de anticoagulación: área bajo la curva ROC 0,57 (IC95%:0,49-0,64, p=0,06). Solo fue útil para las puntuaciones extremas, con probabilidad de buen control del 65,1% vs. 34,9%, p=0,01 para valor 0 y del 0% vs. 100%, p=0,03 para ≥ 4. La razón de disparidad de tener un tiempo en rango terapéutico <65% para puntuación ≥2 fue de 1,22 (IC95%:0,73-2,02, p=0,44). Conclusión: en una cohorte de pacientes con fibrilación auricular no valvular y datos de la vida real la escala SAMe-TT2R2 no mostró, globalmente, capacidad discriminatoria para control adecuado de anticoagulación con antagonistas de vitamina K. Solo se mostró útil para clasificar correctamente los casos con puntuaciones extremas.

Abstract Introduction: The SAMe-TT2R2 score has been proposed to predict the quality of anticoagulation with vitamin K antagonists. Objective: To validate the discriminatory power of the SAMe-TT2R2 score real-life in a patient cohort with non-valvular atrial fibrillation. Material and methods: An observational study was conducted on patients with non-valvular atrial fibrillation treated with vitamin K antagonists for at least six months. Good anticoagulation control was considered a time in the therapeutic range of ≥ 65%, estimated with the Rosendaal method. The relationship between the SAMe-TT2R2 score and the anticoagulation control was evaluated using a binary logistic regression. The discriminatory power was determined using the calculation of the value of the area under the ROC curve. Results: The study included total of 241 patients, with a mean age of 78.6±8.6 years, and 53% women. The mean time in the therapeutic range was 59.4±25.4%, low according to the increase in the SAMe-TT2R2 score. In general, the scale did not appear to have the power to discriminate patients with adequate anticoagulation control, with an area under the ROC curve of 0.57 (95% CI: 0.49-0.64, P=.06). It was only useful for extreme scores, with a probability of good control of 65.1% vs. 34.9%, P=.01 for a value of 0, and of 0% vs. 100%, P=.03 for ≥ 4. The disparity ratio of having a time in the therapeutic range of <65% for a score ≥2 was 1.22 (95% CI: 0.73-2.02, P=.44). Conclusion: In a cohort of patients with non-valvular atrial fibrillation and with real-life data, the SAMe-TT2R2 scale, did not, on the whole, show discriminatory power for the adequate control of anticoagulation with vitamin K antagonists. It only showed to be useful to correctly classify the cases with extreme scores.

Prevalencia de fibrilación auricular y características de la fibrilación auricular no valvular en la población general. Registro AFINVA / Prevalence of atrial fibrillation and features of non-valvular atrial fibrillation in general population

Resumen Fundamento y objetivos: La fibrilación auricular es la arritmia mantenida más común. El estudio pretende conocer la prevalencia de fibrilación auricular en la población general, y evaluar las características y el manejo de los casos con fibrilación auricular no valvular. Métodos: Estudio transversal exploratorio en una muestra de la población de un Departamento de Salud (n = 30.024) de sujetos mayores de 18 años con diagnóstico electrocardiográfico de fibrilación auricular en la historia clínica electrónica de atención primaria. Se analizan características clínicas, manejo y tratamiento. Resultados: De un total de 629 pacientes con diagnóstico de fibrilación auricular, lo que representa una prevalencia del 2,1% (8,06% en > 65 años), fueron seleccionados para el estudio 505 casos con fibrilación auricular no valvular. La edad media fue 77,4 ± 10 años, 55% mujeres. Se objetivó cardiopatía estructural en el 32% de casos e insuficiencia cardiaca en el 29,5%. El 72% de pacientes recibía tratamiento anticoagulante, 60% con antivitamina K y 12% con anticoagulantes directos. Entre los primeros, solo el 53% mantenía un tiempo en rango terapéutico ≥ 65% según el método de Rosendaal. La forma de presentación persistente-permanente fue más frecuente (60,8%), seguida de la paroxística (39,2%). Conclusiones: La prevalencia de fibrilación auricular fue del 2,1%, aumentando con la edad, con elevada proporción de cardiopatía concomitante. La proporción de pacientes anticoagulados y la calidad de la anticoagulación son deficientes, revelándose así la necesidad de mejor monitorización y mayor utilización de nuevos anticoagulantes directos en los casos indicados.

Abstract Background and objectives: Atrial fibrillation is the most common type of constant arrhythmia. The study aims to know the prevalence of atrial fibrillation in the general population and to assess the features and management of non-valvular atrial fibrillation. Methods: Cross-sectional exploratory study of a population sample from a Health department (n=30.024) of individuals over 18 years with electrocardiographic diagnosis of atrial fibrillation in the primary care electronic medical records. Clinical features, management and treatments are analyzed. Results: Out of a total of 629 patients with an atrial fibrillation diagnosis, which represents a 2.1% prevalence (8.06% in >65 years), 505 cases with non-valvular atrial fibrillation were selected for the study. Average age was 77.4 ± 10 years, 55% female patients. Structural heart disease was detected in 32% of the cases, and cardiac failure in 29.5% of the cases. 72% of the patients were receiving anticoagulation therapy, 60% with antivitamin K drugs and 12% with direct anticoagulants. Among the former group, only 53% kept a time within the therapeutic range ≥65% according to the Rosendaal method. The most frequent presentation was persistentpermanent (60.8%), followed by paroxysmal (39.2%). Conclusions: Prevalence of atrial fibrillation was 2.1%, increasing with age, with a high proportion of accompanying heart disease. The proportion of anticoagulated patients and the quality of anticoagulation were poor, thus revealing the need for improved monitoring and wider use of new direct anticoagulants in the indicated cases.