Protocol for a multicentre and prospective follow-up cohort study of early detection of atrial fibrillation, silent stroke and cognitive impairment in high-risk primary care patients: the PREFA-TE study.

BACKGROUND: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Future estimations suggest an increase in global burden of AF greater than 60% by 2050. Numerous studies provide growing evidence that AF is not only associated with stroke but also with cognitive impairment and dementia. AIM: The main goal is to assess the impact of the combined use of cardiac rhythm monitoring devices, echocardiography, biomarkers and neuroimaging on the early diagnosis of AF, silent strokes and cognitive decline, in subjects at high risk of AF. METHODS AND ANALYSIS: Two-year follow-up of a cohort of individuals aged 65-85 years at high risk for AF, with no prior diagnosis of either stroke or dementia. The study involves baseline echocardiography, biomarkers, and neuroimaging, yearly cardiac monitoring, and semiannual clinical assessments. Different parameters from these tests will be analysed as independent variables. Throughout the study period, primary outcomes: new diagnoses of AF, stroke and cognitive impairment, along with any clinical and therapeutic changes, will be registered. A first descriptive and bivariate statistical analysis, appropriate to the types of variables, will be done. The information obtained from the data analysis will encompass adjusted risk estimates along with 95% confidence intervals. Event risk predictions will rely on multivariate Cox proportional hazards regression models. The predictive value of the model will be evaluated through the utilisation of receiver operating characteristic curves for area under the curve calculation. Additionally, time-to-event analysis will be performed using Kaplan-Meier curves. ETHICS AND DISSEMINATION: This study protocol has been reviewed and approved by the Independent Ethics Committee of the Foundation University Institute for Primary Health Care Research-IDIAP Jordi Gol (expedient file 22/090-P). The authors plan to disseminate the study results to the general public through various scientific events. Publication in open-access journals and presentations at scientific congresses, seminars and meetings is also foreseen. TRIAL REGISTRATION NUMBER: NCT05772806.

Risk of Atrial Fibrillation, Ischemic Stroke and Cognitive Impairment: Study of a Population Cohort ≥65 Years of Age.

PURPOSE: To evaluate a model for calculating the risk of AF and its relationship with the incidence of ischemic stroke and prevalence of cognitive decline. MATERIALS AND METHODS: It was a multicenter, observational, retrospective, community-based study of a cohort of general population ≥6ct 35 years, between 01/01/2016 and 31/12/2018. Setting: Primary Care. Participants: 46,706 people ≥65 years with an active medical history in any of the primary care teams of the territory, information accessible through shared history and without previous known AF. Interventions: The model to stratify the risk of AF (PI) has been previously published and included the variables sex, age, mean heart rate, mean weight and CHA2DS2VASc score. Main measurements: For each risk group, the incidence density/1000 person/years of AF and stroke, number of cases required to detect a new AF, the prevalence of cognitive decline, Kendall correlation, and ROC curve were calculated. RESULTS: The prognostic index was obtained in 37,731 cases (80.8%) from lowest (Q1) to highest risk (Q4). A total of 1244 new AFs and 234 stroke episodes were diagnosed. Q3-4 included 53.8% of all AF and 69.5% of strokes in men; 84.2% of all AF and 85.4% of strokes in women; and 77.4% of cases of cognitive impairment. There was a significant linear correlation between the risk-AF score and the Rankin score (p < 0.001), the Pfeiffer score (p < 0.001), but not NIHSS score (p 0.150). The overall NNS was 1/19. CONCLUSION: Risk stratification allows identifying high-risk individuals in whom to intervene on modifiable risk factors, prioritizing the diagnosis of AF and investigating cognitive status.

Risk of Long-Term Mortality for Complex Chronic Patients with Intracerebral Hemorrhage: A Population-Based e-Cohort Observational Study.

INTRODUCTION: Over recent years there has been growing evidence of increased risk of mortality associated with hemorrhagic stroke among older patients. The main objective of this study is to propose and validate a prognostic life table for complex chronic patients after an intracerebral hemorrhage (ICH) episode in primary care settings. METHODS: This was a multicenter and retrospective study (April 1, 2006-December 31, 2016) of a cohort from the general population presenting an episode of ICH from which a predictive model of mortality was obtained using a Cox proportional hazards regression model. In addition, Kaplan-Meier survival curves, the log-rank test, receiver operating characteristic (ROC) curves, and area under the ROC curve (AUC) were used to evaluate the ability to stratify patients according to vital prognosis. We proceeded to external validation of the model through prospective monitoring (January 1, 2013-December 31, 2017) of the population of complex chronic patients with an episode of ICH. RESULTS: A total of 3594 people aged ≥ 65 years were identified as complex chronic patients (women 55.9%; mean age, 86.1 ± 8.4 years) of whom 161 suffered hemorrhagic stroke during the study period (January 1, 2013-December 31, 2017). The primary outcome was death from any cause within 5 years of follow-up after an ICH episode. The independent prognostic factors of mortality were age > 80 years (HR 1.048, 95% CI 1.021-1.076, p < 0.001) and HAS-BLED score (HR 1.369, 95% CI 1.057-1.774, p = 0.017). Compared to the general population, the incidence density/1000 person per year (15 vs 0.22) was significantly higher with a significantly lower annual lethality rate (17% vs 49.2%); and both the prognostic factors and the risk of stratified mortality showed different epidemiological patterns. The internal validation of the model was optimal (log-rank < 0.0001) in the general population, but its external validation was not significant in the complex chronic patient population (log-rank p = 0.104). CONCLUSIONS: The ICH-AP is a clinical scale that can improve the prognostic prediction of mortality in primary care after an episode of ICH in the general population, but it was not significant in its external validation in a population of complex chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03247049.

Long-Term Survival After Stroke According to Reperfusion Therapy, Cardiovascular Therapy and Gender.

BACKGROUND: A wide variety of factors influence stroke prognosis, including age, stroke severity and comorbid conditions; but most current information about outcomes and safety is derived from patients at 3 - 12 months and mostly coming from the hospital activity. The aim of this study is to evaluate whether treatment strategies have a differential impact on long-survival after acute ischemic stroke among men versus women. METHODS: Acute ischemic stroke patients identified from the population-based register between January 1, 2011 and December 31, 2012 were included, and they were classified into: 1) Acute ischemic stroke + intravenous thrombolysis (group I); 2) Acute ischemic stroke + mechanical thrombectomy with or without intravenous thrombolysis (group II); 3) Acute ischemic stroke + medical therapy alone (no reperfusion therapies) (group III). Follow-up went through up until December 2016. The probability of survival was estimated by the Kaplan-Meier method, and the hazard ratio was obtained by using the Cox proportional hazard regression models. Mortality was interpreted as overall mortality. RESULTS: A total of 14,368 cases (men 50.1%), 77.1 ± 11.0 years old were included. There was higher survival among those treated with intravenous thrombolysis (P < 0.001); women treated with thrombectomy (P < 0.001); and women < 80 years old without reperfusion therapy. The most common medications were antiplatelets (52.8%), associated with lower survival (P < 0.001); and statins (46.5%), associated with higher survival. The regression model produced the following independent outcome variables associated to mortality: anticoagulant hazard ratio (HR) 1.53 (95% confidence interval (95% CI): 1.44 - 1.63, P < 0.001), diuretics HR 1.71 (95% CI: 1.63 - 1.79, P < 0.001), antiplatelet HR 1.49 (95% CI: 1.42 - 1.56, P < 0.001), statins HR 0.73 (95% CI: 0.70 - 0.77; P < 0.001), angiotensin II receptor antagonists HR 0.93 (95% CI: 0.89 - 0.98, P = 0.008) and reperfusion therapy HR 0.88 (95% CI: 0.81 - 0.97, P = 0.009). CONCLUSIONS: Men and women have different prognoses after revascularization treatment for acute ischemic stroke. Under 80 years old the women appear to have a better outcome than men when treated with thrombolysis therapy and/or catheter-based thrombectomy. The chronic cardiovascular pharmacotherapy must be evaluated whether they should be included as factors in the decision to reperfusion.

Sex Differences in Long-Term Survival after a First Stroke with Intravenous Thrombolysis: Ebrictus Study.

BACKGROUND: A number of large trials have confirmed the benefits of thrombolysis in acute stroke, but there are gender differences. We sought to examine the relationship between sex and outcome after thrombolysis. METHODS: This was a prospective cohort study including 1,272 incident ischemic strokes (597 in women) from April 1, 2006 to December 31, 2014. Statistical approaches were used for analyzing survival outcomes and their relationship with thrombolysis therapy. RESULTS: The death rates were lower (p = 0.003) in the thrombolysis therapy group with an incidence ratio of 0.57 (95% CI 0.39-0.83). 113 (8.8%) patients (53 women) received thrombolysis. They were significantly younger (69.2 ± 12.7 vs. 73.9 ± 12.5 years; p < 0.001), had higher NIHSS score (12.7 ± 6.3 vs. 7.3 ± 7.0; p < 0.001), spent more days in hospital (10.4 ± 8.3 vs. 8.3 ± 7.9; p < 0.001), and had a higher average Barthel score at discharge (85.5 ± 24.4 vs. 79.2 ± 28.6; p = 0.023). The male/female incidence ratio showed a significant decrease (p = 0.01) in the incidence of mortality in women and a better Barthel score. The thrombolysis improved the survival in the overall group with thrombolysis versus without thrombolysis (p = 0.028), in women versus in men with thrombolysis (p = 0.023), and in women with thrombolysis versus in those without thrombolysis (p < 0.001) but not in men with thrombolysis versus in those without thrombolysis (p = 0.743). The protective factors as regards mortality were thrombolysis therapy (95% CI 0.37-0.80; p = 0.002), Barthel score ≥ 60 (95% CI 0.81-0.94; p = 0.002), and cardiovascular secondary prevention 1 year after stroke (0.13, 95% CI 0.06-0.28). CONCLUSIONS: The stroke death rates were lower in women after thrombolysis treatment and suggest significant benefit for women in this setting. The overall benefit on survival of the patients treated with thrombolysis might be explained by the beneficial effect of the thrombolysis on the women.

Diferencias en la supervivencia después de un episodio de ictus tratado con fibrinólisis. Estudio Ebrictus / Differences in the survival after an episode of stroke treated with thrombolytic therapy. Study Ebrictus

OBJETIVO: Investigar la relación entre género y supervivencia después de un episodio de ictus tratado con fibrinólisis. DISEÑO: Estudio de cohortes. Emplazamiento: Atención primaria. PARTICIPANTES: Los casos tratados con fibrinólisis por un ictus agudo desde el 1 de abril de 2006 al 13 de septiembre de 2013. INTERVENCIONES: Seguimiento del estado vital. MEDICIONES PRINCIPALES: Riesgos vasculares: escala Framingham, REGICOR, CHA2DS2-VASc, Essen, NIHSS, índice Barthel; densidad de incidencia; análisis de supervivencia por Kaplan-Meier; bivariado entre supervivientes y fallecidos; y multivariante de Cox. RESULTADOS: Noventa y un pacientes con edad media 68,02 ± 11,9 años. Los hombres tienen mayor riesgo cardiovascular basal. El tiempo medio de seguimiento fue de 2,95 ± 2,33 años. La razón de tasa de incidencias mostró un mayor riesgo en los hombres respecto a las mujeres IR = 3,2 (IC 95%: 1,2-8,0). Los fallecidos en relación con los supervivientes son mayores (p = 0,032); mayor riesgo cardiovascular basal (p = 0,040) y de recidiva de ictus (p < 0,001); mayor severidad del episodio (p = 0,002); y una mayor caída en la puntuación Barthel un año después del ictus (p = 0,016). El porcentaje de muertes es significativamente más alto cuando el paciente es derivado a centros de agudos o de larga estancia (p = 0,006) que cuando se deriva al domicilio, pero solo el género (HR: 1,12; IC 95%: 1,05-1,20) y la prevención cardiovascular secundaria (HR: 0,13; IC 95%: 0,06-0,28) se asociaron con la mortalidad de los pacientes. CONCLUSIONES: Después de un episodio de ictus tratado con fibrinólisis los hombres tienen un 12% más de riesgo de morir que las mujeres, y la ausencia de prevención cardiovascular secundaria aumenta 7,7 veces el riesgo de mortalidad

OBJECTIVE: To seek if there is gender survival difference among patients treated with thrombolytic therapy. DESIGN: Cohort study. LOCATION: Community based register. PARTICIPANTS: 91 subjects with an episode of stroke collected since April 2006 up to September 2013 and treated with thrombolytic therapy. INTERVENTIONS: Monitoring of vital status. Measurements: We collected baseline characteristics in Framingham, Regicor, CHA2DS2-VASc, Essen, NIHSS, Barthel scales and outcomes according to gender; person-time incidence rate; survival analysis by Kaplan-Meier's curves, bivariate analysis between survivors and deaths, and Cox multivariate. RESULTS: 91 patients with middle age 68.02 ± 11.9 years. The men have higher cardiovascular basal risk. The average time of follow-up was 2.95 ± 2.33 years. Incidence rate ratio (IR) shown higher risk in men than in women IR = 3.2 (CI 95% 1.2-8.0). The dead cases were older (P = .032); with higher cardiovascular basal risk (P = .040) and more risk of stroke recurrence (P = < .001), with cardiovascular pathology before the stroke (P = .005); more stroke severity (P = .002); and a major fall in the score Barthel one year after the episode (P = .016). The percentage of deaths is significantly higher when the patient is referred by complications to other centres (P = .006) in relation to those referred to home, but just the gender (HR: 1,12; IC 95%: 1,05-1,20) and secondary cardiovascular prevention (HR: 0,13; IC 95%: 0,06-0,28) were associated with higher risk of mortality. CONCLUSIONS: After stroke episode treated with thrombolytic therapy, men have 12% higher risk of dying than women and don't be treated with secondary cardiovascular prevention rise 7.7 times the mortality risk

[Differences in the survival after an episode of stroke treated with thrombolytic therapy. Study Ebrictus]. / Diferencias en la supervivencia después de un episodio de ictus tratado con fibrinólisis. Estudio Ebrictus.

OBJECTIVE: To seek if there is gender survival difference among patients treated with thrombolytic therapy. DESIGN: Cohort study. LOCATION: Community based register. PARTICIPANTS: 91 subjects with an episode of stroke collected since April 2006 up to September 2013 and treated with thrombolytic therapy. INTERVENTIONS: Monitoring of vital status. MEASUREMENTS: We collected baseline characteristics in Framingham, Regicor, CHA2DS2-VASc, Essen, NIHSS, Barthel scales and outcomes according to gender; person-time incidence rate; survival analysis by Kaplan-Meier's curves, bivariate analysis between survivors and deaths, and Cox multivariate. RESULTS: 91 patients with middle age 68.02±11.9 years. The men have higher cardiovascular basal risk. The average time of follow-up was 2.95±2.33 years. Incidence rate ratio (IR) shown higher risk in men than in women IR=3.2 (CI 95% 1.2-8.0). The dead cases were older (P=.032); with higher cardiovascular basal risk (P=.040) and more risk of stroke recurrence (P=<.001), with cardiovascular pathology before the stroke (P=.005); more stroke severity (P=.002); and a major fall in the score Barthel one year after the episode (P=.016). The percentage of deaths is significantly higher when the patient is referred by complications to other centres (P=.006) in relation to those referred to home, but just the gender (HR: 1,12; IC 95%: 1,05-1,20) and secondary cardiovascular prevention (HR: 0,13; IC 95%: 0,06-0,28) were associated with higher risk of mortality. CONCLUSIONS: After stroke episode treated with thrombolytic therapy, men have 12% higher risk of dying than women and don't be treated with secondary cardiovascular prevention rise 7.7 times the mortality risk.

Atrial Fibrillation and Cardiovascular Comorbidities, Survival and Mortality: A Real-Life Observational Study.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia encountered in clinical practice affecting up to 10% of the population over 60 years old and its prevalence rises with age. The main goals were to characterize the AF patient population after the initial diagnosis of AF and to determine overall survival. METHODS: It is a real-life observational study of 269 subjects with an AF diagnosis over 60 years old randomly selected. The collected variables were: sociodemographic, cardiovascular complications/comorbidities (CVCs) included in the CHA2DS2-VASc and HAS_BLED scores, drug assigned as clinical treatment, mean range INR and CVCs and death dates (all-cause mortality). The survival curve and the risk of death were assessed using Kaplan-Meier survival curve and comparisons with log-rank. RESULTS: The average following time was 6.2 ± 3.7 years (0.2-20.4). Eleven point five percent died. Sixty-five point four percent had some CVCs. There were no differences in the overall incidence of CVCs by gender. The survival probability was 0.86 ± DE 0.03 among men and 0.90 ± DE 0.04 among women without differences. Thirty-six point eight percent (95% CI: 30.8 - 42.7) were diagnosed vascular complications before AF diagnosis, being ischemic cardiopathy (24.2%) and ischemic stroke (23.2%) the most frequent. The mortality is higher (P < 0.036) among those who suffered ≥ 3 vascular complications and significantly lower among those treated with statins (P = 0.032). After AF diagnosis, the most frequent was the cardiac heart failure (46.7%), significantly higher among women (P = 0.037). The mortality is significantly lower in those treated with OAC (P = 0.003). CONCLUSIONS: AF is associated with ischemic heart disease, ischemic stroke and congestive heart failure, but the average mortality age is not different from the global population in Spain and Catalonia.

La atención sanitaria del ictus en el área Terres de l’Ebre desde la implantación del Código Ictus: Estudio Ebrictus / The stroke care system in Terres de l’Ebre, Spain, after the implementation of the Stroke Code model: Ebrictus Study

Fundamento y objetivo: El objetivo de este análisis es conocer las características del proceso asistencial y detectar posibles problemas del funcionamiento del Código Ictus (CI) en sus 2 primeros años de implementación a partir de la incidencia poblacional de ictus en un sector territorial del Plan Director de Enfermedades Cerebrovasculares. Pacientes y método: Estudio prospectivo de cohorte constituida por personas con un primer episodio de ictus, entre 15-89 años de edad. Se realizó un análisis de los indicadores clínicos de resultados según los requerimientos del CI territorial, y de supervivencia por curvas de Kaplan-Meier y bivariante entre pacientes fallecidos y supervivientes. Resultados: Se incluyeron 380 pacientes ≤80 años, activándose el CI en el 54,3% (IC 95%: 49,0-59,3), intrahospitalariamente en el 77% de casos. El 80% de la ventana terapéutica se consume hasta la llegada al hospital. En el 13,9% (IC 95%: 9,2-19,8) se trató con fibrinólisis. La mortalidad inmediata fue del 9,9% (IC 95%: 7,5-12,5). Conclusiones: La implantación del CI es un sistema que mejoró la atención precoz del ictus en todo el territorio, pero su activación en el ámbito de atención primaria fue baja (AU)

Background and objective: We aimed to know the characteristics of the urgent stroke assistance system, the Stroke Code (SC) model, 2 years after its implementation through testing the specific impact on several result indicators on individuals with a first stroke. Patients and method: Prospective study of a cohort who suffered a first stroke episode, 15 to 89-year-old. Several clinical indicators were selected to evaluate results according to the SC and an analysis survival for Kaplan-Meier's curves was made as well as a bivariate analysis between dead and surviving patients. Data were collected by a community based registry. Results: A total of 380 patients ≤80-year-aged were enrolled and the SC was activated in 54.3% (CI95%: 49,0-59.3), 77% at the hospital. An 80% of the therapeutic window was wasted before arrival to hospital. In 13.9% (CI95%: 9,2-19,8) thrombolysis was used. The immediate mortality was 9.9% (CI95%: 7.5-12.5). Conclusions: The implantation of the SC is a system that improved the welfare chain of stroke in the whole territory, but its activation in the area of primary care was low (AU)

[The stroke care system in Terres de l'Ebre, Spain, after the implementation of the Stroke Code model: Ebrictus Study]. / La atención sanitaria del ictus en el área Terres de l'Ebre desde la implantación del Código Ictus: Estudio Ebrictus.

BACKGROUND AND OBJECTIVE: We aimed to know the characteristics of the urgent stroke assistance system, the Stroke Code (SC) model, 2 years after its implementation through testing the specific impact on several result indicators on individuals with a first stroke. PATIENTS AND METHOD: Prospective study of a cohort who suffered a first stroke episode, 15 to 89-year-old. Several clinical indicators were selected to evaluate results according to the SC and an analysis survival for Kaplan-Meier's curves was made as well as a bivariate analysis between dead and surviving patients. Data were collected by a community based registry. RESULTS: A total of 380 patients ≤80-year-aged were enrolled and the SC was activated in 54.3% (CI95%: 49,0-59.3), 77% at the hospital. An 80% of the therapeutic window was wasted before arrival to hospital. In 13.9% (CI95%: 9,2-19,8) thrombolysis was used. The immediate mortality was 9.9% (CI95%: 7.5-12.5). CONCLUSIONS: The implantation of the SC is a system that improved the welfare chain of stroke in the whole territory, but its activation in the area of primary care was low.