Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study.

BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.

Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results.

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA2DS2-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Acute endovascular reperfusion treatment in patients with ischaemic stroke and large-vessel occlusion (Denmark 2011-2017).

BACKGROUND AND PURPOSE: Acute endovascular reperfusion treatment (aERT) of stroke patients with large-vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011-2017. METHODS: National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography-verified large-vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System. RESULTS: During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3-month follow-up, an modified Rankin Scale score of 0-2 was reported in 46% of patients, whereas 14% of patients had died. CONCLUSION: Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.

Mechanical Thrombectomy with the Embolus Retriever with Interlinked Cages in Acute Ischemic Stroke: ERIC, the New Boy in the Class.

BACKGROUND AND PURPOSE: The Embolus Retriever with Interlinked Cages (ERIC) device is a novel stent retriever for mechanical thrombectomy. It consists of interlinked cages and could improve procedural benchmarks and clinical outcome compared with classic stent retrievers. This study compares the rates of recanalization, favorable clinical outcome, procedural adverse events, and benchmarks between the ERIC device and classic stent retrievers. MATERIALS AND METHODS: From 545 patients treated with thrombectomy between 2012 and 2015, 316 patients were included. The mean age was 69 ±13 years, the mean baseline NIHSS score was 17 ± 5, and 174 (55%) were men. The ERIC was used as the primary thrombectomy device in 59 (19%) patients. In a propensity score matched analysis including the NIHSS score, clot location, delay to groin puncture, neurointerventionalist, and anesthetic management, 57 matched pairs were identified. RESULTS: Patients treated with the ERIC device compared with classic stent retrievers showed equal rates of recanalization (86% versus 81%, P = .61), equal favorable 3-month clinical outcome (mRS 0-2: 46% versus 40%, P = .71), and procedural adverse events (28% versus 30%, P = 1.00). However, in patients treated with the ERIC device, thrombectomy procedures were less time-consuming (67 versus 98 minutes, P = .009) and a rescue device was needed less often (18% versus 39%, P = .02) compared with classic stent retrievers. CONCLUSIONS: Mechanical thrombectomy with the ERIC device is effective and safe. Rates of favorable procedural and clinical outcomes are at least as good as those with classic stent retrievers. Of note, the ERIC device might be time-saving and decrease the need for rescue devices. These promising results call for replication in larger prospective clinical trials.

Rationale and design of INTERSTROKE: a global case-control study of risk factors for stroke.

UNLABELLED: Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. METHODS: INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (+/-5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood samples and random urine samples are obtained from cases and controls. Study Significance: An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.

Prestroke physical activity is associated with severity and long-term outcome from first-ever stroke.

OBJECTIVE: To determine whether prestroke level of physical activity influenced stroke severity and long-term outcome. METHODS: Patients included into the present analyses represent a subset of patients with first-ever stroke enrolled into the ExStroke Pilot Trial. Patients with ischemic stroke were randomized in the ExStroke Pilot Trial to an intervention of repeated instructions and encouragement to increase the level of physical activity or to a control group. Prestroke level of physical activity was assessed retrospectively by interview using the Physical Activity Scale for the Elderly (PASE) questionnaire. The PASE questionnaire quantifies the amount of physical activity done during a 7-day period. In this prospectively collected patient population initial stroke severity was measured using the Scandinavian Stroke Scale and long-term outcome was assessed after 2 years using the modified Rankin Scale. Statistical analyses were done using ordinal logistic regression. RESULTS: Data from 265 patients were included with a mean (SD) age of 68.2 (12.2) years. Confirming univariable analyses, multivariable analyses showed that patients with physical activity in the top quartile more likely presented with a less severe stroke, OR 2.54 (95% CI 1.30-4.95), and had a decreased likelihood of poor outcome, OR 0.46 (95% CI 0.22-0.96), compared to patients in the lowest quartile. CONCLUSIONS: In the present study physical activity prior to stroke was associated with a less severe stroke and better long-term outcome.

Standard method for developing stroke registers in low-income and middle-income countries: experiences from a feasibility study of a stepwise approach to stroke surveillance (STEPS Stroke).

BACKGROUND: Stroke is a leading global cause of death, with an estimated 5.8 million fatal events in 2005, two-thirds of which happened in low-income and middle-income countries. In these regions, epidemiological methods to establish hospital-based stroke registers for clinical audit or studies to estimate incidence are scarce. Our aim was to ascertain whether stroke registers could be set up in geographically diverse populations in low-income and middle-income countries, using standardised data-collection manuals and methods, before recommending their wider use. METHODS: WHO's stepwise approach to stroke surveillance (STEPS Stroke) offers an entry point for countries to register stroke patients in health-information systems. The methods proposed in this strategy were tested in a feasibility study, which focused on hospitalised stroke patients in nine different surveillance sites located in five low-income and middle-income countries. Data collection was for a median of 12 months. Observed differences between men and women were adjusted for age and surveillance site with logistic-regression analyses. FINDINGS: A total of 5557 stroke patients were registered; 91 people whose age was missing or younger than 15 years were excluded from the analyses. Mean age was 64.2 years (SD 14.6), and 2484 (45%) participants were women. Ischaemic stroke accounted for about two-thirds of events. Half of all patients were hospitalised the same day. Stroke subtype was verified in 4913 (90%) participants by diagnostic techniques. Women had lower odds of verification of stroke subtype compared with men after adjustment for age and surveillance site (odds ratio 0.69 [95% CI 0.56-0.86]; p=0.0006). INTERPRETATION: STEPS Stroke can be used in diverse populations to provide data in a standardised manner in countries with little or no previous records of stroke. Future studies should concentrate on expansion beyond hospital case series by adding information for stroke patients treated outside the hospital, linked to census data for the source population from which the cases come.

Stroke incidence and prevalence in Europe: a review of available data.

Reliable data on stroke incidence and prevalence are essential for calculating the burden of stroke and the planning of prevention and treatment of stroke patients. In the current study we have reviewed the published data from EU countries, Iceland, Norway, and Switzerland, and provide WHO estimates for stroke incidence and prevalence in these countries. Studies on stroke epidemiology published in peer-reviewed journals during the past 10 years were identified using Medline/PubMed searches, and reviewed using the structure of WHO's stroke component of the WHO InfoBase. WHO estimates for stroke incidence and prevalence for each country were calculated from routine mortality statistics. Rates from studies that met the 'ideal' criteria were compared with WHO's estimates. Forty-four incidence studies and 12 prevalence studies were identified. There were several methodological differences that hampered comparisons of data. WHO stroke estimates were in good agreement with results from 'ideal' stroke population studies. According to the WHO estimates the number of stroke events in these selected countries is likely to increase from 1.1 million per year in 2000 to more than 1.5 million per year in 2025 solely because of the demographic changes. Until better and more stroke studies are available, the WHO stroke estimates may provide the best data for understanding the stroke burden in countries where no stroke data currently exists. A standardized protocol for stroke surveillance is recommended.

Is the effect of alcohol on risk of stroke confined to highly stressed persons?

BACKGROUND: Psychological stress and alcohol are both suggested as risk factors for stroke. Further, there appears to be a close relation between stress and alcohol consumption. Several experimental studies have found alcohol consumption to reduce the immediate effects of stress in a laboratory setting. We aimed to examine whether the association between alcohol and stroke depends on level of self-reported stress in a large prospective cohort. METHODS: The 5,373 men and 6,723 women participating in the second examination of the Copenhagen City Heart Study in 1981-1983 were asked at baseline about their self-reported level of stress and their weekly alcohol consumption. The participants were followed-up until 31st of December 1997 during which 880 first ever stroke events occurred. Data were analysed by means of Cox regression modelling. RESULTS: At a high stress level, weekly total consumption of 1-14 units of alcohol compared with no consumption seemed associated with a lower risk of stroke (adjusted RR: 0.57, 95% CI: 0.31-1.07). At lower stress levels, no clear associations were observed. Regarding subtypes, self-reported stress appeared only to modify the association between alcohol intake and ischaemic stroke events. Regarding specific types of alcoholic beverages, self-reported stress only modified the associations for intake of beer and wine. CONCLUSIONS: This study indicates that the apparent lower risk of stroke associated with moderate alcohol consumption is confined to a group of highly stressed persons. It is suggested that alcohol consumption may play a role in reducing the risk of stroke by modifying the physiological or psychological stress response.

Lung function and risk of fatal and non-fatal stroke. The Copenhagen City Heart Study.

BACKGROUND: Reduced lung function has been shown to be a significant predictor of non-fatal ischaemic heart disease, and of mortality due to cardiovascular disease. Fewer studies have analysed the relationship between lung function and risk of fatal or non-fatal stroke. The present study presents results on the relation between forced expiratory volume in one second (FEV1) and risk of incident and fatal first-ever stroke. SUBJECTS AND METHODS: The analyses are based on prospective cohort data from 12 878 eligible men and women aged 45-84 years, who participated in the first health examination of the Copenhagen City Heart Study in 1976-1978. The subjects were followed from day of entry until 31 December 1993. During that period 808 first-ever strokes occurred of which 153 were fatal within 28 days. Risk of incident and fatal stroke was estimated by means of Cox hazard regression. The analyses included adjustment for potential confounders: sex, age, smoking, inhalation, body mass index, systolic blood pressure, triglycerides, physical activity in leisure time, education, diabetes mellitus, and antihypertensive treatment. RESULTS: We found an inverse association between FEV1 and risk of first-time stroke. For each 10% decrease in FEV1 in percentage of expected, the relative risk (RR) increased 1.05 (95% CI : 1.00-1.09, P = 0.03). This represents an approximately 30% higher risk of stroke in the group of people with the lowest lung function as compared to the group with the highest lung function. The association between lung function and risk of fatal stroke resembled that of risk of incident stroke (fatal and non-fatal). The RR was 1.11 (95% CI : 1.03-1.19) for each 10% decrease in FEV1 in percentage of expected. This represents approximately a doubling of the risk between the highest and lowest lung function groups. CONCLUSIONS: This study shows that reduced lung function measured in percentage of predicted FEV1 is a predictor of first-time stroke and fatal stroke independent of smoking and inhalation. The high risk of fatal first-ever stroke in the group of people with low lung function may be of significance in both the design and interpretation of clinical trials.

Surveillance of stroke: a global perspective.

For preventive strategies to be efficient, it is essential to have information on the pattern of disease and exposure to major risk factors that predict future diseases in the population. Basic epidemiological data such as mortality rates are reported for less than one-third of the world's population and are almost exclusively from developed countries. However, it is the developing countries, particularly those in rapid economic and demographic transition, which will experience a major rise in ageing-related diseases. The World Health Organization is intensifying the development and implementation of simple, sustainable surveillance systems that can be used in many different settings around the world. Unlike heart disease and cancer, stroke is a clinically defined disease, which makes it possible to identify trends in different countries irrespective of access to technological equipment. A stepwise approach to increasing detail in the data to be collected for surveillance of stroke is suggested. This will allow countries with different levels of resources and capacity in their health systems to collect useful information for policy.

Prevention of recurrent stroke.

There is a considerable knowledge about risk factors for first ever stroke and a lack of knowledge about risk factors for recurrent stroke. As neurologists we rarely see the patient before the first transient ischemic attack (TIA) or stroke, and we are concerned with and need data on secondary stroke prevention. For lifestyle factors such as cigarette smoking, physical activity and alcohol consumption, data are scarce. For post-menopausal estrogen use there are no data on risk of recurrent stroke. Plasma homocysteine has emerged as a risk factor for stroke and cardiovascular disease. It is not yet documented if supplementation of folic acid, which may reduce plasma homocysteine, also lowers risk of stroke. Elevated blood pressure is a risk factor for recurrent stroke. There are four randomized trials of antihypertensive treatment after stroke indicating a tendency of reduced risk of stroke recurrence. Three studies of antihypertensive treatment after first stroke are in progress. Prevention of recurrent stroke is well documented in atrial fibrillation where warfarin is highly beneficial and aspirin has some effect. Carotid endarterectomy in high grade carotid artery stenosis is also well documented. Antiplatelet therapy provides secondary prevention in most types of ischemic brain disease.

Passive smoking as well as active smoking increases the risk of acute stroke.

OBJECTIVE: To estimate the relative risk of stroke associated with exposure to environmental tobacco smoke (ETS, passive smoking) and to estimate the risk of stroke associated with current smoking (active smoking) using the traditional baseline group (never-smokers) and a baseline group that includes lifelong non-smokers and long-term (> 10 years) ex-smokers who have not been exposed to ETS. DESIGN AND SETTING: Population-based case-control study in residents of Auckland, New Zealand. SUBJECTS: Cases were obtained from the Auckland stroke study, a population-based register of acute stroke. Controls were obtained from a cross-sectional survery of major cardiovascular risk factors measured in the same population. A standard questionnaire was administered to patients and controls by trained nurse interviewers. RESULTS: Information was available for 521 patients with first-ever acute stroke and 1851 community controls aged 35-74 years. After adjusting for potential confounders (age, sex, history of hypertension, heart disease, and diabetes) using logistic regression, exposure to ETS among non-smokers and long-term ex-smokers was associated with a significantly increased risk of stroke (odds ratio (OR) = 1.82; 95% confidence interval (95% CI) = 1.34 to 2.49). The risk was significant in men (OR = 2.10; 95% CI = 1.33 to 3.32) and women (OR = 1.66; 95% CI = 1.07 to 2.57). Active smokers had a fourfold risk of stroke compared with people who reported they had never smoked cigarettes (OR = 4.14; 95% CI = 3.04 to 5.63); the risk increased when active smokers were compared with people who had never smoked or had quit smoking more than 10 years earlier and who were not exposed to ETS (OR = 6.33; 95% CI = 4.50 to 8.91). CONCLUSIONS: This study is one of the few to investigate the association between passive smoking and the risk of acute stroke. We found a significantly increased risk of stroke in men and in women. This study also confirms the higher risk of stroke in men and women who smoke cigarettes compared with non-smokers. The stroke risk increases further when those who have been exposed to ETS are excluded from the non-smoking reference group. These findings also suggest that studies investigating the adverse effects of smoking will underestimate the risk if exposure to ETS is not taken into account.

Intake of beer, wine, and spirits and risk of stroke : the copenhagen city heart study.

BACKGROUND AND PURPOSE: Alcohol consumption has been associated with a protective effect on risk of ischemic stroke. There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic that has gained only little attention in stroke research. METHODS: Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years, participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were analyzed by means of multiple Poisson regression. RESULTS: We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke compared with no wine intake (monthly: relative risk [RR], 0. 83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45 to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR, 0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke. CONCLUSIONS: The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the wine in addition to ethanol are responsible for the protective effect on risk of stroke.

Changes in subarachnoid hemorrhage mortality, incidence, and case fatality in New Zealand between 1981-1983 and 1991-1993.

BACKGROUND AND PURPOSE: As with total stroke, mortality rates from subarachnoid hemorrhage (SAH) have declined in New Zealand since the mid-1970s. Data from the Auckland Region Stroke studies allow an understanding of reasons for the change, as SAH incidence and 28-day case fatality rates were measured as part of population-based stroke registers. METHODS: National death registrations were used to describe the trends in mortality rates from SAH (International Classification of Diseases [ICD] code 430) among men and women in New Zealand. Changes in incidence and case fatality rates were determined from 2 large-scale population-based stroke registries carried out in 1981-1983 and 10 years later in Auckland. Similar methodology and case ascertainment techniques were used in both studies. RESULTS: The mortality rates from SAH declined in both men and women after the mid-1970s. The mortality rate remained higher among women than men. The incidence of SAH was lower in 1991-1993 (11.3 per 100,000) compared with 1981-1983 (14.6 per 100,000). In the younger age groups, the decrease was mostly due to a lower incidence among men, whereas in the older age groups women older than 65 years had a lower incidence. There was no consistent change in case fatality rates between the 2 periods in either men or women. CONCLUSIONS: Mortality rates from SAH have decreased in both men and women. This decrease may be explained by a decrease in the incidence of SAH, because case fatality rates showed no change.