Atrial fibrillation as an independent risk factor for stroke: the Framingham Study

The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial fibrillation. For persons aged 80-89 years, atrial fibrillation was the sole cardiovascular condition to exert an independent effect on stroke incidence (p less than 0.001). The attributable risk of stroke for all cardiovascular contributors decreased with age except for atrial fibrillation, for which the attributable risk increased significantly (p less than 0.01), rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years. While these findings highlight the impact of each cardiovascular condition on the risk of stroke, the data suggest that the elderly are particularly vulnerable to stroke when atrial fibrillation is present.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective study of atrial fibrillation and stroke

In a prospective study of 72 patients with stroke and atrial fibrillation, we classified strokes as cardioembolic or noncardioembolic based on arterial assessment using Doppler sonography and angiography. We analyzed and cross-tabulated 18 clinical characteristics and found four to be significantly associated with a cardioembolic mechanism: stroke with onset during activity and peak deficit at onset (p less than 0.008), previous infarct in a different vascular territory (p less than 0.01), previous transient ischemic attack in a different vascular territory (p less than 0.01), and transient ischemic attack lasting greater than 1 hour (p less than 0.02). Starting with these four characteristics, we used a step-down procedure to select variables for a logistic regression model. Only previous infarct in a different vascular territory (odds ratio = 7.38) and transient ischemic attack lasting greater than 1 hour (odds ratio = 7.89) were selected by the model. Using M-mode and two-dimensional echocardiography, we compared left atrial size in 46 patients with that in 78 controls who had atrial fibrillation without stroke. Left atrial size in patients and controls with mitral valvulopathy was significantly larger than that in patients and controls without mitral valve disease. There was, however, no difference in left atrial size between patients with nonvalvular atrial fibrillation and cardioembolic stroke and controls or patients with nonvalvular atrial fibrillation and noncardioembolic stroke. We concluded that some clinical characteristics are closely related to cardioembolic stroke and that left atrial enlargement reflects underlying cardiopathy rather than atrial emboli-forming capability.     

Non-rheumatic atrial fibrillation as a risk factor for stroke

The association between non-rheumatic atrial fibrillation (AF) and stroke has been studied in 402 patients consecutively admitted to a stroke unit. Brain infarction patients with sinus rhythm (n = 196) and non-rheumatic AF (n = 92) were further compared. Some findings supported an embolic origin of the stroke: half of the deceased AF patients (n = 24) at autopsy either had left atrial thrombosis or arterial embolism compared to none of the ten with sinus rhythm. Patients with AF also had a higher mortality and more severe brain lesions, findings compatible with a sudden occlusion of blood flow. However, these differences might also be explained by an atherothrombotic occlusion with impaired autoregulation in the ischaemic region in conjunction with heart failure, which was more common in the AF patients. Other findings supporting an atherothrombotic mechanism were: the prevalence of AF was higher (19-29%) in all kinds of stroke, including haemorrhage, than in age-matched controls (3-9%). Also patients with previous AF and no present embolic source resembled the whole AF group and differed from patients with sinus rhythm. Thus embolism is a plausible cause of stroke in many AF patients, whereas an atherothrombotic origin is more likely in others. Characteristics identifying the mechanism in an individual case were not found.     

Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation

We studied whether hemostatic abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. Hemostatic function was studied in four age-matched groups: 20 patients with nonvalvular atrial fibrillation and a previous ischemic stroke, 20 patients with nonvalvular atrial fibrillation without a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Both groups with nonvalvular atrial fibrillation had significantly higher concentrations of von Willebrand factor, factor VIII:C, fibrinogen, D-dimer (a fibrinolytic product), beta-thromboglobulin, and platelet factor 4; a significantly higher fibrinogen/antithrombin ratio; and significantly higher spontaneous amidolytic activity than the healthy controls. Prekallikrein levels were significantly lower in both groups with nonvalvular atrial fibrillation. Stroke patients with sinus rhythm had normal hemostatic function, normal concentrations of platelet-related factors, and a slightly increased concentration of fibrinopeptide A compared with the healthy controls. Both groups with nonvalvular atrial fibrillation differed from the stroke patients with sinus rhythm as they did from the healthy controls. No difference in hemostatic function was seen between the nonvalvular atrial fibrillation patients with and without a previous ischemic stroke. Thus, alterations in hemostatic function may contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation.     

Transient atrial fibrillation and risk of stroke after acute myocardial infarction

Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI). In the AMI setting, AF is frequently brief and attributed to acute haemodynamic changes, inflammation or ischaemia. However, it remains uncertain whether transient AF episodes are associated with a subsequent increased risk of ischaemic stroke. We studied the impact of transient new-onset AF on the one-year risk of ischaemic stroke or transient ischaemic attack (TIA) in a retrospective cohort of 2,402 patients with AMI. Patients with previous AF or AF at hospital discharge were excluded. Transient AF occurred in 174 patients (7.2%) during the initial hospitalisation. During one year follow-up after hospital discharge, stroke or TIA occurred in 16 (9.2%) and 58 (2.6%) patients with and without transient AF, respectively (p< 0.0001). Compared with patients without transient AF, the adjusted hazard ratio for stroke or TIA in patients with transient AF was 3.03 (95% CI 1.73-5.32; p< 0.0001). Stroke or TIA occurred in 2.6% of patients without AF, 6.3% of patients with transient AF treated with oral anticoagulants, and 9.9% of patients with transient AF treated with antiplatelet agents. The incidence of recurrent AF after hospital discharge was markedly higher in patients with transient AF during the index hospitalisation (22.8% vs. 2.0%, p< 0.0001). In conclusion, transient AF complicating AMI is associated with an increased future risk of ischaemic stroke and TIA, particularly in patients treated with antiplatelet agents alone. High AF recurrence rates in these patients also suggest that oral anticoagulants should be strongly considered.     

Lone atrial fibrillation and stroke

We studied 21 consecutive patients from the Lausanne Stroke Registry, who had first-ever ischemic stroke and lone atrial fibrillation, with a standard protocol of investigations including brain CT, and non-invasive cardiac and arterial tests. Rarity of associated risk factors and extracranial; arterial disease, presence of distal intracerebral occlusions on early angiography, and topography of cerebral infarct suggested that cardioembolism was the cause of stroke, though echocardiographic evidence for an atrial thrombus was uncommon. There was no recurrence during a post-stroke 14-day phase, during which anticoagulant and antiaggregant therapies were systematically avoided. Though low, the main risk of stroke recurrence was 0.99 per 100 patient-years during a mean follow-up period of 4.8 years, including a mean duration of anticoagulant therapy of 2.3 years in 18 patients. On the other hand, no death, severe cardiac events, or disabling anticoagulation-related hemorrhages occurred.     

Ischemic stroke and atrial fibrillation. A clinical study

In view of the higher prevalence of severe ischemic stroke among patients with atrial fibrillation (AF) and of the recently reported higher frequency of stroke with AF in females, 516 consecutive patients with ischemic stroke, of whom 93 had AF, were retrospectively evaluated. The main anamnestic, clinical and laboratory features of the AF and non-AF groups were statistically compared and the features of the AF group were statistically evaluated according to gender and age. Our results confirm the greater severity of stroke in AF patients than in non-AF patients and the higher frequency of stroke with AF in female patients. Moreover, a significantly higher frequency of stroke with AF was found in the male 60–69 and the female 80–89 age groups than in the other age groups. Relevant risk factors in females aged 80–89 were hypertension and left ventricular hypertrophy (LVH), while diabetes, alcohol, smoking and LVH prevailed among 60–69 year old males.

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Sommario Sono stati esaminati retrospettivamente 516 pazienti consecutivi affetti da ictus ischemico, di cui 93 con fibrillazione atriale (AF), al fine di valutare la maggiore incidenza di ictus ischemico grave nei pazienti con fibrillazione atriale (AF), così come la maggiore frequenza di ictus associati a AF nel sesso femminile. Sono stati confrontati statisticamente i principali dati anamnestici, clinici e laboratoristici dei due gruppi di pazienti, AF e non-AF. Inoltre, sono state valutate statisticamente le caratteristiche del gruppo AF, secondo il sesso e l'età. I nostri risultati confermano l'esistenza di una maggiore gravità dell'ictus nei pazienti con AF rispetto a quelli non-AF, così come una maggiore incidenza di ictus associati a AF nel sesso femminile. Inoltre, è stata riscontrata una frequenza significativamente maggiore di ictus associati a AF nei soggetti maschi di età compresa fra 80–89 anni. Fattori di rischio rilevanti nelle femmine di età 80–89 anni erano costituiti dall'ipertensione e dall'ipertrofia ventricolare sinistra (LVH), mentre il diabete, l'alcool, il fumo e l'LVH erano presenti nei maschi di età 60–90 anni.

     

Gapless Electrocardiogram-Monitoring in stroke at high risk of atrial fibrillation

Background and purpose

Previous studies investigating prolonged electrocardiogram (ECG)-monitoring after ischemic stroke had significant gaps between the index event and the beginning of long-term monitoring. Atrial fibrillation (AF) detection might be higher if prolonged cardiac rhythm documentation is performed with a gapless approach without any interruption of monitoring time.

Methods

This investigator-initiated, prospective study included patients with acute ischemic stroke or transient ischemic attack at three study centers. Participants received gapless ECG-monitoring via telemetry during stroke-unit admission until implantation of an insertable cardiac monitor (ICM) within the first days after the index event. Patients acted as their own controls and also received standard 24–72-h Holter ECG.

Results

A total of 110 patients were included, of whom 86 (78.2%) had an embolic stroke of unknown source, 14 (12.7%) had small-vessel disease, and 10 (9.1%) had large-artery disease. AF was newly diagnosed in 17 (15.5%) patients via ICM monitoring, compared to one (0.9%) patient via Holter ECG during 6 months of follow-up (p < 0.001). The detection rate of AF within the first 30 days was 10.0%, which accounted for 64% of all new AF diagnoses. The median duration of the detected episodes was 1.7 (interquartile range = 0.2–4.7) h. All patients with new onset AF were treated with oral anticoagulation.

Conclusions

Gapless ECG-monitoring is an effective strategy to significantly increase the detection rate of AF after ischemic stroke. This finding supports the use of long-term ECG-monitoring with a gapless approach without any interruption in monitoring time as the gold standard for clinical practice.     

Is atrial fibrillation an independent risk factor for stroke?

That non-rheumatic atrial fibrillation is an independent risk factor for cerebral infarction has not been established with certainty. The rationale underlying contemporary clinical trials of warfarin therapy for the prevention of stroke in patients who have non-rheumatic atrial fibrillation is that the majority of strokes in such patients are due to cardiogenic cerebral embolism. However, there is evidence to suggest that the increased probability of stroke attributed to this arrhythmia is due to its association with other risk factors such as hypertension, diabetes mellitus, and atherosclerosis. The question of who should be anticoagulated is a major public health issue since atrial fibrillation is present in approximately ten per cent of the general population aged 65 or more years.     

Risk assessment and anticoagulation for primary stroke prevention in atrial fibrillation.

BACKGROUND AND PURPOSE: Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF). METHODS: A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated. RESULTS: The mean+/-SD age of 234 patients was 67.1+/-11.8 years, and 122 (52%) were women. Clinical risk factors were present in 74 of 80 patients (92%) aged >75 years compared with 99 of 154 patients (64%) 75 years of age, and was associated with clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72 of 154 (47%) to 105 of 154 (68%) patients aged 75 years, regardless of criteria used (P<0.01). Warfarin was being used in 55 of 105 patients (51%) 75 years (P<0.001). Anticoagulation was being undertaken in 7 of 49 patients (14%) 相似文献   

Markers of thrombin and platelet activity in patients with atrial fibrillation: correlation with stroke among 1531 participants in the stroke prevention in atrial fibrillation III study

BACKGROUND AND PURPOSE: Markers of thrombin generation and platelet activation are often elevated in patients with nonvalvular atrial fibrillation, but it is unclear whether such markers usefully predict stroke. Therefore, we undertook the present study to assess the relationship between prothrombin fragment F1.2 (F1.2), beta-thromboglobulin (BTG), fibrinogen, and the factor V Leiden mutation with stroke in atrial fibrillation. METHODS: Specimens were obtained from 1531 participants in the Stroke Prevention in Atrial Fibrillation III study. The results were correlated with patient features, antithrombotic therapy, and subsequent thromboembolism (ischemic stroke and systemic embolism) by multivariate analysis. RESULTS: Increased F1.2 levels were associated with age (P<0.001), female sex (P<0.001), systolic blood pressure (P=0.006), and heart failure (P=0.001). F1.2 were not affected by aspirin use and were not associated with thromboembolism after adjustment for age (P=0. 18). BTG levels were higher with advanced age (P=0.006), coronary artery disease (P=0.05), carotid disease (P=0.005), and heart failure (P<0.001), lower in regular alcohol users (P=0.05), and not significantly associated with thromboembolism. Fibrinogen levels were not significantly related to thromboembolism but were associated with elevated BTG levels (P<0.001). The factor V Leiden mutation was not associated with thromboembolism (relative risk 0.5, 95% CI 0.1 to 3.8). CONCLUSIONS: Elevated F1.2 levels were associated with clinical risk factors for stroke in atrial fibrillation, whereas increased BTG levels were linked to manifestations of atherosclerosis. In this large cohort of patients with atrial fibrillation who were receiving aspirin, F1.2, BTG, fibrinogen, and factor V Leiden were not independent, clinically useful predictors of stroke.     

Probability of stroke: a risk profile from the Framingham Study

A health risk appraisal function has been developed for the prediction of stroke using the Framingham Study cohort. The stroke risk factors included in the profile are age, systolic blood pressure, the use of antihypertensive therapy, diabetes mellitus, cigarette smoking, prior cardiovascular disease (coronary heart disease, cardiac failure, or intermittent claudication), atrial fibrillation, and left ventricular hypertrophy by electrocardiogram. Based on 472 stroke events occurring during 10 years' follow-up from biennial examinations 9 and 14, stroke probabilities were computed using the Cox proportional hazards model for each sex based on a point system. On the basis of the risk factors in the profile, which can be readily determined on routine physical examination in a physician's office, stroke risk can be estimated. An individual's risk can be related to the average risk of stroke for persons of the same age and sex. The information that one's risk of stroke is several times higher than average may provide the impetus for risk factor modification. It may also help to identify persons at substantially increased stroke risk resulting from borderline levels of multiple risk factors such as those with mild or borderline hypertension and facilitate multifactorial risk factor modification.     

Detection of atrial fibrillation after stroke

Approximately every fourth stroke results from cardiac embolism. Atrial fibrillation has been recognized as a common cause for thromboembolic stroke. Detection of unknown atrial fibrillation is an important clinical challenge, as anticoagulation may effectively reduce the risk of recurrent ischemic stroke. In all patients with a cryptogenic stroke 24-h Holter monitoring should be performed in addition to a standard ECG to detect paroxysmal atrial fibrillation. In addition, it is useful to pay attention to atrial fibrillation during continuous bedside ECG monitoring on the stroke unit and in pacemaker interrogation. The indication for longer ECG monitoring by implantable loop recorders may be considered individually based on the expected probability of atrial fibrillation. The potential benefit of these devices is currently being evaluated in clinical trials.