Risk Factors And Screening Methods For Atrial Fibrillation In Ischemic Stroke And Transient Ischemic Attack Patients

Background and objectiveStroke is a set of local or overall brain function deficiency syndrome caused by acute cerebral circulatory disturbance, including Ischemic Stroke and Hemorrhagic Stroke. Ischemic stroke is cerebral infarction; Hemorrhagic stroke including cerebral hemorrhage and subarachnoid hemorrhage.Stroke is of high morbidity, high mortality andhighincidence of disability and recurrence.The TOAST criteria are the most frequently used classification of stroke in epidemiological or genetic studies and refer to(1) large-artery atherosclerosis (artery-to-artery embolus, large artery atherothrombosis), (2) cardiac embolism, (3) cerebral small artery occlusion (lacunar stroke), (4) stroke of another determined aetiology (rare aetiologies), and (5) stroke of undetermined aetiology. Embolism from a cardiac source accounts for 15-30% approximately of these cerebral events. The most frequent causes of cardiogenic stroke are AF, left ventricular (LV) dysfunction (congestive heart failure), valve disease and prosthetic valves, intracardiac right-to-left shunts (PFO, particularly in conjunction with atrial septum aneurysm), and atheromatous thrombosis of the ascending aortic arch. From an epidemiological point of view, there is a history of AF in around one half of cases, of valvular heart disease in one-fourth, and of LV mural thrombus in almost a third.Atrial fibrillation is one of the most common arrhythmias. According to a large-scale epidemiological study in China, AF total prevalence rate is of 0.65% in the general population, of 7.5% in the people over the age of 80, it is estimated that at least 8 million patients with atrial fibrillation in our country. AF is one of the most important independent risk factor for ischemic stroke, it lead to five times of stroke than in people without AFs. A lot of data shows the paroxysmal and persistent AF patients exhibited similar thromboembolic risk.A systematic review and meta-analysis about 32 studies revealed that the overall detection rate of any new AF was 11.5%after ischemic stroke or transient ischemic attack.In 2010 a multicenter cross-sectional survey study in our country showsthe proportion of Ischemic stroke/transient ischemic attack (TIA) patients with AF is 4.7%(108/2283), much lower than the international average level. Paroxysmal AF (PAF) is often undetected because characteristics such as short duration, episodic, and frequently asymptomatic nature make it challenging to diagnose at the bedside, leading to missed diagnosis and suboptimal secondary prevention. It is likely that a proportion of strokes labeled as cryptogenic are cardioembolic in origin because of occult AF. Furthermore,≥2 factors contributing to stroke risk may coexist:even patients with an identified risk factor for nonembolic stroke may have occult cardioembolism.Anticoagulation therapy initiated after detection of atrial fibrillation (AF) provides an additional 40% risk reduction of stroke as compared to antiplatelet therapy alone.Current advances in the detection of paroxysmal atrial fibrillationincludingl2-leadelectrocardiogram, continuous eletrocardiographic monitoring, Holter, Loop recorder (LR), insertable cardiac monitor (ICM),Intermittent short ECG recording and so on.ECG recording is the most direct and definite diagnostic method of atrial fibrillation, the longer monitoring, the moredetection of AF. But some testing instrument has not spread at the grassroots in our country, and the invasive, high costof some devices limits its application in the general population. Fortunately,detection rates were higher in selected than in unselected patients, and methods of score can be used for preliminary screening.The clearly evaluation method mainly includes:(1)STAF score:calculated from the sum of the points for the 4 items (possible total score 0 to 8):age >62 years (2 points); NIHSS>or=8 (1 points); left atrial dilatation (2 points); absence of symptomatic intraorextracranial stenosis> or=50%, or clinico-radiological lacunar syndrome (3 points).STAF>or=5 identified patients with AF with a sensitivity of 89% and a specificity of 88%. (2)ASAS score:This scorecan also be applied to patients with TIA. Significant predictors of atrial fibrillation included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. ASAS=-6+Age/20+NIHSS/10+0.9*LAE. For this model, the area under the receiver operating characteristic curve was 0.76. According to Pr=eASAS/(1+eASAS), a Pr values>0.09 targets AF with a sensitivity of 86.11% and specificity of 56.86%.(3)LADS score:This is a 6-point scoring system based on left atrial diameter<35mm(0point),35-44mm(lpoint),>or=45mm(2points); age<60(0point), 60-79(1 point),> or=80(2points);diagnosis, TIA(Opoint), stroke(lpoint); and a history of smokingwithin the previous year,Yes(0point), No(lpoint). A score of 4 or greater was associated with a sensitivity of 85.5% and a specificity of 53.1%.Furthermore, Brain natriuretic peptide, Troponin-I, Left ventricular diastolic dysfunction can also be a relevant marker to rule out delayed atrial fibrillation in stroke or transient ischemic attack patient.The three scoring methods have advantages and disadvantages. STAF is of high sensitivity and specificity in patients withischemic stroke, whether it is suitable for the TIAs isuncertain because such patients were not included in that study. The system requires expertise in the application of the NIHSS stroke scale score and the TOAST criteria for stroke etiological classification, which is not widely available in most hospitals.Further, there are significant inter-rater reliability variations for the NIH stroke scale score and and TOAST classification which might affect the sensitivity and specificity of this scoring system in other settings.ASAS score was also suitable for the TIAs as well as ischemic strokes.But the analyses was according to the use of both transthoracic and transesophageal echocardiography, which have different sensitivities for the detection of cardiac abnormalities.The LADS score, based on simple criteria, is suitable for promotion.However, it is based on a retrospective, single-center study and was not validated any further. Therefore, the broader applicability of this score is uncertain.Only the effect of STAF was confirmed in China at present, two other scoring methods have not been verified at home, therefore, which is the better method of screening atrial fibrillation in domestic ischemic stroke/TIA population, has not yet been determined.This study retrospectively analyzed ischemic stroke or transient ischemic attack patients in Nanfang Hospital between January 2012 and December 2012. Patients who are hemorrhagic stroke, who not evaluated with transthoracic echocardiograms were excluded from the analyses.A total of 291 patients with acute ischemia stroke or TIA were included,255 cases without atrial fibrillation,36 cases with atrial fibrillation. Looking for asuitablescreening method by comparing LADS score, STAF score, ASAS score and related results of examination, to optimize screening strategies,improvedetection rates in selectedpatients, and search for the best economic benefit.Methods1.Patient selection1.1 Consecutive stroke and TIA patients over the age of 18 who were admitted between January 2012 and December 2012 were the target group for this study.1.2 Inclusion criteria:(1) Patientsdiagnosis of ischemic stroke and TIA;(2) The definition of AF included a previous diagnosis based on patient recall confirmed by the attending physician or by documentation of the first episode of paroxystic, persistent, permanent, or long-standing AF during hospitalization through ECG, Holter monitoring, or continuous eletrocardiographic monitoring; (3) At least 18 years of age; (4) Admitted to hospital within 7 days of symptom onset.1.3 Exclusion criteria:(1) Admitted to hospital beyond7 days of symptom onset;(2) Patients not evaluated with transthoracic echocardiograms.1.4 Group Standard:Patients were divided into 2 groups according to the existence of atrial fibrillation or not.2.Study designBaseline medical variables collected included age, gender,a reported history of hypertension, diabetes, smoking within the past year, prior strokes, hyperlipidemia, atrial fibrillation, congestive heart failure, drug therapy. The NIHSS score at admission, and the classification according to TOAST is also included.Laboratory dataincludedblood routine examination, coagulation function, blood lipid test, renal function, Homocysteine.Echocardiographic data included left atrial diameter (LAD), left ventricular internal dimension at the end of diastole (LVIDd), left ventricular internal dimension at the end of systole (LVIDs),Mitral valve blood flow velocity, left ventricular ejection fraction, and ejection fraction (EF).The ASAS,STAF and LADS scores are calculate according to criteria. Compare area under the ROC curve (AUC) for different models.3.Statistical analysisStatistic analysis was conducted by SPSS17.0.Descriptive statistical analysis, Independent-Sample T Test,x2 tests, Logistic regression, ROC curve were used in the study, All tests were two tailed, and significant levels were defined as P<0.05 is all statistical analyses.Results1. Clinical data statistics1.1 General clinical outcome:Of the 291 patients,255 were without AFs and 36 were with AFs.191 were males and 100 were females, the mean age of our patients was 62±13.65 years, range 21-90 years.the mean time from symptom onset to admitted to hospital was 49.53±45.3 hours, range 2 hours to 7 days.1.2 Other diseases combined:smoking was presented in 105 patients,smoking within the past year in 99 patients, Congestive heart failure in 20 patients, Hypertension was presented in 207 patients, Diabetes in 90 patients, prior strokes in 28 patients, Hyperlipidemia in 155 patients, Hyperuricemia in 96 patients, Hyperhomocysteinemia in 68 patients.1.3 Treatment:In patients without AFs,12 cases were treated with thrombolytic agent,164 cases were treated with Aspirin or clopidogrel alone,82 cases were treated with Aspirin and clopidogrel,2cases were treated with Warfarin,7 cases didn’t receive anticoagulant therapy because of Gastrointestinal hemorrhage; In patients with AFs,1 case was treated with thrombolytic agent,13 cases were treated with Warfarin,13 cases were treated with Aspirin or clopidogrel alone,9 cases were treated with Aspirin and clopidogrel,1 cases didn’t receive anticoagulant therapy because of Gastrointestinal hemorrhage.1.4 TOAST classification:251 cases of ischemic stroke were classified according to TOAST:(1)95 cases of large-artery atherosclerosis (LAA), (2) 75 cases of cerebral small artery occlusion (SAO), (3) 37 cases of cardiac embolism (SE), (4) 42 casesof stroke of undetermined aetiology (SUD), and (5) 2 cases of stroke of other determined aetiology (SOD).2. Comparison between AFs and NAFs:A significant difference between AFs and NAFs at the ratio of smoking within the past year(16.7% vs.36.5%,P=0.019), of smoking(19.4% vs.38.4%,P=0.026), of hypertension(52.8% vs.73.7%,P=0.009),of hyperlipidemia(33.3% vs.56.1%, P=0.011); age(68.28±13.18 vs.61.12±13.51, P=0.003),NIHSS(7.22±4.79 vs.3.95±3.10,P<0.001), LAD(41.72±8.22 vs. 31.62±4.06,P<0.001), LVIDs(29.99±7.20 vs.26.67±5.60,P=0.02), FS(34.83±8.10 vs. 38.83±7.54,P=0.007), EF(63.48±11.08 vs.68.36±10.37,P=0.012), TG(1.24±0.78 vs. 1.69±1.05,P=0.023),CHOL(4.64±1.33 vs.5.09±1.16,P=0.046),platelet(195.71±56.70 vs.227.61±67.92,P=0.008).3. Multivariate analysis of AF:Multivariate logistic regression analysis showed age (P=0.012,OR=1.053),NIHSS(P=0.001,OR=1.229), and LAD (P<0.001,OR=1.364) are risk factors for AF in ischemic stroke and TIA patients.4. ROC curve of ASAS, STAF, LADS to predict AF:The area under the ROC curve of three methods to predict AF shows:LADS is 0.846, ASAS is 0.835,STAF is 0.801, according to Pr=eASAS/(1+eASAS), A LADS score of 4 or greater was associated with a sensitivity of 66.67% and a specificity of 85.10%. A Pr values>0.09 targets AF with a sensitivity of 86.11% and specificity of 56.86%. A STAF score of 5 or greater was associated with a sensitivity of 61.11% and a specificity of 77.65%.LADS>4 shows a better accuracy among those scores.Conclusion1. Age, NIHSS, and LAD are main risk factors for AF in ischemic stroke and TIA patients.2. Both STAF, LADS,and ASAS can be used to screen AF in Chinese people.3. LADS>4 shows a better accuracy among those scores. Since it is based on simple criteria, is suitable for promotion.