The rs2108622 polymorphism is related to the early risk of ischemic stroke in non-valvular atrial fibrillation subjects under oral anticoagulation.

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

The determination of copeptin levels helps management decisions among transient ischaemic attack patients.

BACKGROUND: Most approaches to transient ischaemic attack (TIA) triage use clinical scores and vascular imaging; however, some biomarkers have been suggested to improve the prognosis of TIA patients. METHODS: Serum levels of copeptin, adiponectin, neopterin, neuron-specific enolase, high-sensitivity C-reactive protein, IL-6, N-terminal pro-B-type natriuretic peptide, S100ß, tumour necrosis factor-alpha and IL-1α as well as clinical characteristics were assessed on consecutive TIA patients during the first 24 h of the onset of symptoms. RESULTS: Among 237 consecutive TIA patients, 12 patients (5%) had a stroke within 7 days and 15 (6%) within 90 days. Among all candidate biomarkers analysed, only copeptin was significantly increased in patients with stroke recurrence (SR) within 7 days (P = 0.026) but not within 90 days. A cut-off point of 13.8 pmol/l was established with a great predictive negative value (97.4%). Large artery atherosclerosis (LAA) [hazard ratio (HR) 12.7, 95% CI 3.2-50.1, P < 0.001] and copeptin levels ≥13.8 pmol/l (HR 3.9, 95% CI 1.01-14.4, P = 0.039) were independent predictors of SR at the 7-day follow-up. LAA was the only predictor of 90-day SR (HR 7.4, 95% CI 2.5-21.6, P < 0.001). ABCD3I was associated with 7- and 90-day SRs (P = 0.025 and P = 0.034, respectively). The association between copeptin levels and LAA had a diagnostic accuracy of 90.3%. CONCLUSIONS: Serum copeptin could be an important prognostic biomarker to guide management decisions among TIA patients. Therefore, TIA patients with copeptin levels below 13.8 pmol/l and without LAA have an insignificant risk of 7-day SR and could be managed on an outpatient basis.

Prediction of myocardial infarction in patients with transient ischaemic attack.

BACKGROUND: Determinants of risk of myocardial infarction (MI) after transient ischaemic attack (TIA) are not well defined. The aim of our study was to determine the risk and risk factors for MI after TIA. METHODS: We prospectively recruited patients within 24 h of transient ischaemic cerebrovascular events between October 2006 and January 2013. A total of 628 TIA patients were followed for six months or more. MI and stroke recurrence (SR) were recorded. The duration and typology of clinical symptoms, vascular risk factors and aetiological work-ups were prospectively recorded and established prognostic scores (ABCD2, ABCD2I, ABCD3I, Essen Stroke Risk Score, California Risk Score and Stroke Prognosis Instrument) were calculated. RESULTS: Twenty-eight (4.5%) MI and 68 (11.0%) recurrent strokes occurred during a median follow-up period of 31.2 months (16.1-44.9). In Cox proportional hazards multivariate analyses, we identify previous coronary heart disease (CHD) (hazard ratio [HR] 5.65, 95% confidence interval [CI] 2.45-13.04, P < 0.001) and sex male (HR 2.72, 95% CI 1.02-7.30, P = 0.046) as independent predictors of MI. Discrimination for the prognostic scores only ranged from 0.60 to 0.71. The incidence of MI did not vary among the different aetiological subtypes. Positive diffusion weighted imaging (DWI) (7.5% vs 2.5%, P = 0.007), and ECG abnormalities (Q wave or ST-T wave changes) (13.6% vs 3.6%, P = 0.001) were associated to MI. CONCLUSION: According to our results, discrimination was poor for all previous risk prediction models evaluated. Variables such as previous CHD, male sex, DWI and ECG abnormalities should be considered in new prediction models.

N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The etiological classification of patients with transient ischaemic attack (TIA) is a difficult endeavor and the use of serum biomarkers could improve the diagnostic accuracy. The aim of this study was to correlate atrial fibrillation, the main cardioembolic etiology (CE), with different serum biomarkers measured in consecutive TIA patients. METHODS: The concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha, neuron-specific enolase, high-sensitivity C-reactive protein, IL-1-α and the N-terminal pro-B type natriuretic peptide (NT-proBNP) were quantified in the serum of 140 patients with TIA and 44 non-stroke subjects. Measurements were performed at different times throughout evolution: within 24 h of symptoms onset and at days 7 and 90. RESULTS: With the exception of IL-6, all biomarkers were higher in TIA patients than in controls. NT-proBNP was significantly related to the presence or new diagnosis of AF at all time points analyzed. Furthermore, the baseline NT-proBNP level was significantly higher than values at the 7-day and 90-day follow-up. For this reason, different cut-off values were obtained at different times: 313 pg/ml at baseline [odds ratio (OR) = 18.99, P < 0.001], 181 pg/ml at 7 days (OR = 11.4, P = 0.001) and 174 pg/ml (OR = 8.46, P < 0.001) at 90 days. CONCLUSION: High levels of NT-proBNP determined during the first 3 months after a TIA were associated with AF. Consequently, this biomarker may be useful to reclassify undetermined TIA patients as having disease of CE.

[Evolution of the degree of disease knowledge in subjects who have suffered an ischaemic stroke]. / Evolución del grado de conocimiento de la enfermedad en pacientes que han sufrido un ictus isquémico.

INTRODUCTION: The delay in seeking medical care in patients who suffer a cerebrovascular disease (CVD) event depends, largely, on knowledge of the disease. Our aim is to study the evolution of the knowledge of patients admitted to hospital due to an ischaemic stroke. PATIENTS AND METHODS: A structured interview was used to determine the level of knowledge of CVD (terminology, risk factors, symptoms and attitude) of patients admitted due to an ischaemic stroke without language impairment or cognitive impairment in two distinct time periods: January 2011 and December 2013 (n = 295), and October 2015 and December 2016 (n = 325). RESULTS: Better knowledge of the disease was observed over time, both in the number of terms recognised - 4.1 (standard deviation: 2) vs. 4.8 (standard deviation: 1.7); p < 0.001 - and in a good knowledge of symptoms (more than three factors and less than two distractors) (56.6 vs. 69.8%; p < 0.001). The proportion of patients who called the emergency services directly was significantly higher (17.3 vs. 24.6%; p = 0.003), as was the recognition of the term 'stroke' (51.9 vs. 74.5%; p < 0.001). There was no difference in the degree of knowledge of risk factors. Improvement in knowledge did not translate into a decrease in the delay between symptom onset and arrival at the hospital. CONCLUSION: Despite improved knowledge of CVD, further efforts still need to be made to improve attitudes towards CVD and reduce the delay prior to hospital arrival.

TITLE: Evolución del grado de conocimiento de la enfermedad en pacientes que han sufrido un ictus isquémico.Introducción. La demora hasta la demanda de la atención médica en pacientes que sufren un episodio de enfermedad cerebrovascular (ECV) depende, en gran parte, del conocimiento que existe de la enfermedad. Pretendemos estudiar la evolución del conocimiento de los pacientes que ingresaron por un ictus isquémico. Pacientes y métodos. Se utilizó una entrevista estructurada para conocer el grado de conocimiento de la ECV (terminología, factores de riesgo, síntomas y actitud) de los pacientes ingresados por ictus isquémico sin trastorno del lenguaje ni alteración cognitiva en dos períodos de tiempo diferenciados: enero de 2011 y diciembre de 2013 (n = 295), y octubre de 2015 y diciembre de 2016 (n = 325). Resultados. Se observó un mejor conocimiento de la enfermedad a lo largo del tiempo, tanto en el número de términos reconocidos ­­4,1 (desviación estándar: 2) frente a 4,8 (desviación estándar: 1,7); p menor de 0,001­ como en el buen conocimiento de los síntomas (más de tres factores y menos de dos distractores) (56,6 frente a 69,8%; p menor de 0,001). La proporción de pacientes que llamaron directamente al 112 fue significativamente mayor (17,3 frente a 24,6%; p = 0,003), así como el reconocimiento del término 'ictus' (51,9 frente a 74,5%; p menor de 0,001). No hubo diferencias en el grado de conocimiento de los factores de riesgo. La mejoría en el grado de conocimiento no se tradujo en una disminución en la demora entre el inicio de los síntomas y la llegada al hospital. Conclusión. Pese a la mejoría en el conocimiento de la ECV, todavía se deben hacer esfuerzos para mejorar la actitud frente a la ECV y disminuir la demora hasta la llegada al hospital.