Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

BACKGROUND AND AIMS: The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. METHODS: A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). RESULTS: Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). CONCLUSIONS: In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study.

BACKGROUND: Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. The present study aimed to assess the association between primary headache disorders and AF. METHODS: In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006-2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs). RESULTS: Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64-1.11) for migraine, 1.16 (95% CI = 0.86-1.27) for TTH and 1.04 (95% CI = 0.86-1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39-0.73). CONCLUSIONS: In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

BACKGROUND: Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements. METHODS: Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity. RESULTS: Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P < 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivaroxaban (both P < 0.001). Factor X antigen measurements in citrate-plasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma. CONCLUSIONS: Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.

Associations between post-stroke motor and cognitive function: a cross-sectional study.

BACKGROUND: Motor and cognitive impairments are frequently observed following stroke, but are often managed as distinct entities, and there is little evidence regarding how they are related. The aim of this study was to describe the prevalence of concurrent motor and cognitive impairments 3 months after stroke and to examine how motor performance was associated with memory, executive function and global cognition. METHODS: The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study is a prospective multicentre cohort study including patients hospitalized with acute stroke between May 2015 and March 2017. The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission. Level of disability was assessed by the Modified Rankin Scale (mRS). Motor and cognitive functions were assessed 3 months post-stroke using the Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (TMT-B), 10-Word List Recall (10WLR), Short Physical Performance Battery (SPPB), dual-task cost (DTC) and grip strength (Jamar®). Cut-offs were set according to current recommendations. Associations were examined using linear regression with cognitive tests as dependent variables and motor domains as covariates, adjusted for age, sex, education and stroke severity. RESULTS: Of 567 participants included, 242 (43%) were women, mean (SD) age was 72.2 (11.7) years, 416 (75%) had an NIHSS score ≤ 4 and 475 (84%) had an mRS score of ≤2. Prevalence of concurrent motor and cognitive impairment ranged from 9.5% for DTC and 10WLR to 22.9% for grip strength and TMT-B. SPPB was associated with MoCA (regression coefficient B = 0.465, 95%CI [0.352, 0.578]), TMT-B (B = -9.494, 95%CI [- 11.726, - 7.925]) and 10WLR (B = 0.132, 95%CI [0.054, 0.211]). Grip strength was associated with MoCA (B = 0.075, 95%CI [0.039, 0.112]), TMT-B (B = -1.972, 95%CI [- 2.672, - 1.272]) and 10WLR (B = 0.041, 95%CI [0.016, 0.066]). Higher DTC was associated with more time needed to complete TMT-B (B = 0.475, 95%CI [0.075, 0.875]) but not with MoCA or 10WLR. CONCLUSION: Three months after suffering mainly minor strokes, 30-40% of participants had motor or cognitive impairments, while 20% had concurrent impairments. Motor performance was associated with memory, executive function and global cognition. The identification of concurrent impairments could be relevant for preventing functional decline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

Physical activity, cardiorespiratory fitness, and cardiovascular outcomes in individuals with atrial fibrillation: the HUNT study.

AIMS: Atrial fibrillation (AF) confers higher risk of mortality and morbidity, but the long-term impact of physical activity (PA) and cardiorespiratory fitness (CRF) on outcomes in AF patients is unknown. We, therefore, examined the prospective associations of PA and estimated CRF (eCRF) with all-cause mortality, cardiovascular disease (CVD) mortality, morbidity and stroke in individuals with AF. METHODS AND RESULTS: We followed 1117 AF patients from the HUNT3 study in 2006-08 until first occurrence of the outcomes or end of follow-up in November 2015. We used Cox proportional hazard regression to examine the prospective associations of self-reported PA and eCRF with the outcomes. Atrial fibrillation patients meeting PA guidelines had lower risk of all-cause [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41-0.75] and CVD mortality (HR 0.54, 95% CI 0.34-0.86) compared with inactive patients. The respective HRs for CVD morbidity and stroke were 0.78 (95% CI 0.58-1.04) and 0.70 (95% CI 0.42-1.15). Each 1-metabolic equivalent task (MET) higher eCRF was associated with a lower risk of all-cause (HR 0.88, 95% CI 0.81-0.95), CVD mortality (HR 0.85, 95% CI 0.76-0.95), and morbidity (HR 0.88, 95% CI 0.82-0.95). CONCLUSION: Higher PA and CRF are associated with lower long-term risk of CVD and all-cause mortality in individuals with AF. The findings support a role for regular PA and improved CRF in AF patients, in order to combat the elevated risk for mortality and morbidity.

Feasibility and Clinical Impact of Point-of-Care Carotid Artery Examinations by Experts using Hand-Held Ultrasound Devices in Patients with Ischemic Stroke or Transitory Ischemic Attack.

BACKGROUND AND PURPOSE: To evaluate the feasibility and clinical influence of carotid artery examinations in patients admitted with stroke or TIA with hand-held ultrasound by experts, to identify individuals not in need of further carotid artery diagnostics. MATERIALS AND METHODS: Cardiologists experienced in carotid ultrasound examined 80 patients admitted to a stroke unit with suspected stroke or TIA with hand-held ultrasound devices (HUD). Grey scale and color Doppler images were stored using a GE Vscan with dual probe (phased array and linear transducer). High-end triplex ultrasound performed by a cardiologist, blinded to the details of the HUD study, was performed in all patients and used as reference. Computer tomography angiography was performed when clinically indicated. RESULTS: Stroke or TIA was diagnosed in 62 (78%) patients. Age was median (range) 72 (23-93) years. A significant stenosis (> 50% diameter reduction) was ruled out in 61 (76%) of patients by the HUD examinations. Sensitivity and specificity for diagnosing a significant stenosis was 92% and 93%, respectively. One of 12 significant stenoses was missed by HUD. All four patients in need of surgery were identified by the HUD examination. Sensitivity and specificity to identify a significant stenosis by HUD was 87% and 83%, respectively, compared to CT angiography. CONCLUSION: HUD examinations of the carotid arteries by experts, using hand-held ultrasound devices, were feasible and may reduce the need for high-end diagnostic imaging of the carotid vessels in patients with stroke and TIA. Thus, HUD may improve diagnostic workflow in stroke units in the future.

Low grade albuminuria as a risk factor for subtypes of stroke - the HUNT Study in Norway.

BACKGROUND AND PURPOSE: Albuminuria is a marker for endothelial dysfunction and knowledge on its association with stroke and stroke subtypes are limited. METHODS: Corresponding data from 7261 participants of the population-based HUNT2 study (1995-1997) was linked with hospital records, identified all patients registered and diagnosed with a first-time stroke. Each diagnosis was validated by reviewal of the medical record appertaining to the individual. We then applied Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between albuminuria (measured as albumin-to-creatinine-ratio, ACR) and diagnosis of stroke and stroke subtypes. RESULTS: 703 (9.7%) participants developed a first ischemic stroke during a median follow-up of 15 years. Higher albuminuria was associated with a higher rate for ischemic stroke and the risk rose steadily with increasing ACR (15% increment per unit increase in ACR concentration in mg/mmol). In the fully adjusted model, the HR for all ischemic strokes was 1.56 (95% CI 1.24-1.95) for those with an ACR ≥3 mg/mmol compared to participants with an ACR < 1 mg/mmol. Overall, increasing ACR was associated with a higher risk of all ischemic stroke subtypes. This was seen to be strongest for lacunar stroke (HR 1.75, CI 1.12-2.72, p = 0.019), and also for stroke of undetermined etiology (HR 1.53, CI 1.11-2.11, p = 0.009) and those caused by atherosclerosis in the large arteries (HR 1.51, CI 0.78-2.94, p = 0.186) than for cardio-embolic stroke (HR 1.22, CI 0.64-2.3, p = 0.518). CONCLUSIONS: Albuminuria is an important risk factor, potentially already at low grade, for ischemic stroke especially for lacunar subtype. Measuring albuminuria is both cheap and readily available. This offers the opportunity to evaluate the risk for endothelial dysfunction and thus the subsequent risk for stroke and cerebral small vessel disease.

Weight and weight change and risk of atrial fibrillation: the HUNT study.

AIMS: Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain. METHODS AND RESULTS: An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0-1.4) for average BMI 25.0-29.9 kg/m2 and 1.6 (1.2-2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened. CONCLUSION: Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.

Factors influencing employment after minor stroke and NSTEMI.

AIM: To study the effect of cognitive function, fatigue and emotional symptoms on employment after a minor ischemic stroke compared to non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS: We included 217 patients with minor ischemic stroke and 133 NSTEMI patients employed at baseline aged 18-70 years. Minor stroke was defined as modified Rankin scale (mRS) 0-2 at day seven or at discharge if before. Included NSTEMI patients had the same functional mRS. We applied a selection of cognitive tests and the patients completed questionnaires measuring symptoms of anxiety, depression and fatigue at follow up. Stroke patients were tested at three and 12 months and NSTEMI at 12 months. RESULTS: The patients still employed at 12 monthswere significantly younger than the unemployed patients and the NSTEMI patients employed were significantly older than the stroke patients (59 vs 55 years, p < .001). In total, 82 % of stroke patients and 90 % of the NSTEMI patients employed at baseline were still employed at 12 months (p = 06). Stroke patients at work after 12 months had higher education than unemployed patients. There were no difference between employed and unemployed patients in risk factors or location of cerebral ischemic lesions. Cognitive function did not change significantly in the stroke patients from three to 12 months. For stroke patients, we found a significant association between HADS-depression and unemployment at 12 months (p = 04), although this association was not present at three months. Lower age and higher educational level were associated with employment at 12 months for all patients. DISCUSSION AND CONCLUSION: Age and education are the main factors influencing the ability to stay in work after a minor stroke. Employed stroke patients were younger than the NSTEMI patients, but there was no difference in the frequencies in remaining employed. The employment rate at 12 months was high despite the relatively high prevalence of cognitive impairment in both groups.

Stroke risk after transient ischemic attack in a Norwegian prospective cohort.

BACKGROUND: Transient ischemic attack (TIA) is a risk factor of stroke. Modern treatment regimens and changing risk factors in the population justify new estimates of stroke risk after TIA, and evaluation of the recommended ABCD2 stroke risk score. METHODS: From October, 2012, to July, 2014, we performed a prospective, multicenter study in Central Norway, enrolling patients with a TIA within the previous 2 weeks. Our aim was to assess stroke risk at 1 week, 3 months and 1 year after TIA, and to determine the predictive value of the dichotomized ABCD2 score (0-3 vs 4-7) at each time point. We used data obtained by telephone follow-up and registry data from the Norwegian Stroke Register. RESULTS: Five hundred and seventy-seven patients with TIA were enrolled of which 85% were examined by a stroke specialist within 24 h after symptom onset. The cumulative incidence of stroke within 1 week, 3 months and 1 year of TIA was 0.9% (95% CI, 0.37-2.0), 3.3% (95% CI, 2.1-5.1) and 5.4% (95% CI, 3.9-7.6), respectively. The accuracy of the ABCD2 score provided by c-statistics at 7 days, 3 months and 1 year was 0.62 (95% CI, 0.39-0.85), 0.62 (95% CI, 0.51-0.74) and 0.64 (95% CI, 0.54-0.75), respectively. CONCLUSIONS: We found a lower stroke risk after TIA than reported in earlier studies. The ABCD2 score did not reliably discriminate between low and high risk patients, suggesting that it may be less useful in populations with a low risk of stroke after TIA. TRIAL REGISTRATION: Unique identifier: NCT02038725 (retrospectively registered, January 16, 2014).

The development of cognitive and emotional impairment after a minor stroke: A longitudinal study.

OBJECTIVES: To study the development of cognitive and emotional symptoms between 3 and 12 months after a minor stroke. MATERIAL AND METHODS: We included patients from stroke units at hospitals in the Central Norway Health Authority and from Haukeland University Hospital. We administered a selection of cognitive tests, and the patients completed a questionnaire 3 and 12 months post-stroke. Cognitive impairment was defined as impairment of ≥2 cognitive tests. RESULTS: A total of 324 patients completed the 3-month testing, whereas 37 patients were lost to follow-up at 12 months. The results showed significant improvement of cognitive function defined as impairment of ≥2 cognitive tests (P = .03) from months 3 to 12. However, most patients still showed cognitive impairment at 12 months with a prevalence of 35.4%. There is significant association between several of the cognitive tests and hypertension and smoking (P = .002 and .05). The prevalence of depression, but not anxiety, increased from 3 to 12 months (P = .04). The prevalence of fatigue did not change and was thus still high with 29.5% after 12 months. CONCLUSIONS: This study shows that an improvement of cognitive function still occurs between 3 and 12 months. Despite this, the prevalence of mostly minor cognitive impairment still remains high 12 months after the stroke. The increasing prevalence of depressive symptoms highlights the importance of being vigilant of depressive symptoms throughout the rehabilitation period. Furthermore, high prevalence of fatigue persisted.

The Norwegian Cognitive impairment after stroke study (Nor-COAST): study protocol of a multicentre, prospective cohort study.

BACKGROUND: Early and late onset post-stroke cognitive impairment (PCI) contributes substantially to disability following stroke, and is a high priority within stroke research. The aetiology for PCI is complex and related to the stroke itself, brain resilience, comorbid brain diseases, prestroke vulnerability and complications during the hospital stay. The aim of the Norwegian Cognitive Impairment After Stroke study (Nor-COAST) is to quantify and measure levels of cognitive impairments in a general Norwegian stroke population and to identify biological and clinical markers associated with prognosis for cognitive disorders following incident stroke. The study will be organised within five work packages: 1) Incidence and trajectories 2) Pathological mechanisms 3) Development of a risk score 4) Impact of physical activity and 5) Adherence to secondary prevention. METHODS: Nor-COAST is an ongoing multicentre (five participating hospitals), prospective, cohort study with consecutive inclusion during the acute phase and with follow-up at three and 18 months, and at three years. Inclusion criteria are stroke defined according to the WHO criteria. During the recruitment period from 18.05.2015 to 31.03.2017, 816 participants have been included. Cognitive impairment will be classified according to the DSM-5 criteria using a consensus group. Cognitive function is assessed by a standardised neuropsychological test battery, the Montreal Cognitive Assessment, Trail making A and B, ten-word immediate and delayed recall test, the Controlled Oral Word Association, Global Deterioration Scale and proxy based information by and the Ascertain Dementia 8 item informant questionnaire. Biomarkers include magnetic resonance imaging, routine blood samples and bio-banking. Clinical assessments include characteristics of the stroke, comorbidity, delirium, frailty and tests for cognitive and physical function, sensor based activity monitoring and adherence to secondary prophylaxis. DISCUSSION: Nor-COAST is the first Norwegian multicentre study to quantify burden of PCI that will provide reliable estimates in a general stroke population. A multidisciplinary approach aiming to identify biomarkers and clinical markers of overall prognosis will add new knowledge about risk profiles, including pre-stroke vulnerability and modifiable factors such as physical activity and secondary prophylaxis of relevance for clinical practice and later intervention studies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531 . Retrospectively registered January 8, 2016. First participant included May 18, 2015.

Risk factors for stroke and choice of oral anticoagulant in atrial fibrillation.

PURPOSE: To investigate risk factors for stroke in patients initiating oral anticoagulants for atrial fibrillation in Norway and their association with receiving DOACs versus warfarin. METHODS: From nationwide registries, we identified naïve users initiating treatment with warfarin, dabigatran, rivaroxaban, or apixaban for atrial fibrillation from 2010 to 2015 in Norway. We studied temporal changes in the CHA2DS2-VASc score and its component risk factors. We used multiple logistic regressions to identify CHA2DS2-VASc risk factors associated with receiving DOACs versus warfarin in 2015. RESULTS: From 2010 to 2015, the yearly number of new oral anticoagulant users increased from 7588 to 13,344. All new users initiated warfarin in 2010, while 86% initiated a DOAC in 2015. The mean CHA2DS2-VASc score decreased from 3.2 (SD 1.7) to 3.1 (SD 1.6) in the same period. Vascular disease (0.56 [0.49-0.63]), congestive heart failure (OR 0.65 [95% CI 0.58-0.72]), and diabetes (0.83 [0.73-0.95]) decreased the odds of receiving DOACs instead of warfarin, and ischemic stroke/transient ischemic attack/arterial thromboembolism (1.31 [1.12-1.54]), age 65-74 (1.23 [1.06-1.43]), and female sex (1.22 [1.10-1.36]) increased it. Age ≥ 75 (reference age < 65) and hypertension had no impact. CONCLUSIONS: The uptake of DOACs was rapid and spurred an increase in new users of oral anticoagulants for atrial fibrillation from 2010 to 2015 in Norway. The mean CHA2DS2-VASc score did not change substantially during this period. Vascular disease, heart failure, and diabetes were associated with initiation of warfarin, and previous stroke, age 65-74 and female sex with initiation of DOACs.

Hospital readmission within 10 years post stroke: frequency, type and timing.

BACKGROUND: The aim of this study was to examine the hospital readmissions in a 10 year follow-up of a stroke cohort previously studied for acute and subacute complications and to focus on their frequency, their causes and their timing. METHODS: The hospital records of 243 patients, 50% of a cohort of 489 patients acutely and consecutively admitted to our stroke unit in 2002/3, were subjected to review 10 years after the incidental stroke and all acute admissions were examined. The main admitting diagnoses were attributed to one of 18 predefined categories of illness. Additionally, the occurrence of death was registered. RESULTS: After 10 years 68.9% of patients had died and 72.4% had been readmitted to the hospital with a mean number of readmissions of 3.4 (+15.1 SD). 20% of the readmissions were due to a vascular cause, 17.3% were caused by infection, 9.3% by falls with (6.1%) and without fracture, 5.7% by a hemorrhagic event. The readmission rate was highest in the first 6 months post stroke with a rate of 116.2 admissions/100 live patient-years. Falls with fractures occurred maximally 3-5 years post stroke. CONCLUSIONS: Hospital readmissions over the 10 years following stroke are caused by vascular events, infections, falls and hemorrhagic events, where the first 6 months are a period of particular vulnerability. The magnitude and the spectrum of these long-term complications suggest the need for a more comprehensive approach to post stroke prophylaxis.

Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015.

PURPOSE: Since 2011, several direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban) have been introduced as alternatives to warfarin for stroke prophylaxis in atrial fibrillation. We wanted to investigate changes in utilization of oral anticoagulants for atrial fibrillation in Norway following the introduction of DOACs. METHODS: Using nationwide registries, we identified all adults with pharmacy dispensings for warfarin or DOACs between January 2010 and December 2015 in Norway, and used ambulatory reimbursement codes to identify atrial fibrillation as indication. We defined incident use by a 1-year washout period. We describe trends in prevalent and incident use of warfarin and DOACs between 2010 and 2015, as well as patterns of treatment switching for incident users. RESULTS: One hundred twenty-nine thousand two hundred eighty-five patients filled at least one prescription for an oral anticoagulant for atrial fibrillation; the yearly number of incident users increased from 262 to 421 per 100,000 person-years; and the yearly share of incident users who initiated a DOAC increased to 82%. Half the prevalent users were on a DOAC by 2015. Within a year of drug initiation, 6, 12, 16 and 20% of incident users of apixaban, rivaroxaban, warfarin and dabigatran, respectively, switched oral anticoagulant. CONCLUSIONS: Use of DOACs for anticoagulation in atrial fibrillation became more prevalent between 2010 and 2015 in Norway, at the expense of warfarin.

Monitoring following acute stroke should be improved. / Overvåkning etter akutt hjerneslag bør bli bedre.

Many serious complications following acute stroke can be prevented and treated. This requires close and systematic monitoring following stroke.