Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study.

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case­control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups­UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29­0.41) and LMIC (aOR 0.50, 95% CI 0.41­0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7­17.8) in HIC, 14.6% (95% CI 12.3­17.1) in UMIC-1, 5.7% (95% CI 4.9­6.7) in UMIC-2, and 6.3% (95% CI 5.3­7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Sleep Patterns and the Risk of Acute Stroke: Results From the INTERSTROKE International Case-Control Study.

BACKGROUND AND OBJECTIVES: Symptoms of sleep disturbance are common and may represent important modifiable risk factors of stroke. We evaluated the association between a spectrum of sleep disturbance symptoms and the risk of acute stroke in an international setting. METHODS: The INTERSTROKE study is an international case-control study of patients presenting with first acute stroke and controls matched by age (±5 years) and sex. Sleep symptoms in the previous month were assessed through a questionnaire. Conditional logistic regression estimated the association between sleep disturbance symptoms and acute stroke, expressed as odds ratios (ORs) and 95% CIs. The primary model adjusted for age, occupation, marital status, and modified Rankin scale at baseline, with subsequent models adjusting for potential mediators (behavioral/disease risk factors). RESULTS: Overall, 4,496 matched participants were included, with 1,799 of them having experienced an ischemic stroke and 439 an intracerebral hemorrhage. Short sleep (<5 hours: OR 3.15, 95% CI 2.09-4.76), long sleep (>9 hours: OR 2.67, 95% CI 1.89-3.78), impaired quality (OR 1.52, 95% CI 1.32-1.75), difficulty getting to sleep (OR 1.32, 95% CI 1.13-1.55) or maintaining sleep (OR 1.33, 95% CI 1.15-1.53), unplanned napping (OR 1.48, 95% CI 1.20-1.84), prolonged napping (>1 hour: OR 1.88, 95% CI 1.49-2.38), snoring (OR 1.91, 95% CI 1.62-2.24), snorting (OR 2.64, 95% CI 2.17-3.20), and breathing cessation (OR 2.87, 95% CI 2.28-3.60) were all significantly associated with an increased odds of acute stroke in the primary model. A derived obstructive sleep apnea score of 2-3 (2.67, 2.25-3.15) and cumulative sleep symptoms (>5: 5.38, 4.03-7.18) were also associated with a significantly increased odds of acute stroke, with the latter showing a graded association. After an extensive adjustment, significance was maintained for most of the symptoms (not difficulty getting to/maintaining sleep and unplanned napping), with similar findings for stroke subtypes. DISCUSSION: We found that sleep disturbance symptoms were common and associated with a graded increased risk of stroke. These symptoms may be a marker of increased individual risk or represent independent risk factors. Future clinical trials are warranted to determine the efficacy of sleep interventions in stroke prevention.

Pleocytosis in cerebrospinal fluid attributed to ischemic stroke: A review of the literature.

INTRODUCTION: Lumbar puncture is generally performed in stroke settings when infectious or inflammatory diseases are suspected to be the etiology. This review aimed to assess the prevalence of pleocytosis in the cerebrospinal fluid following ischemic stroke without inflammatory or infectious etiology. METHODS: We searched PubMed for studies with mentions of "[ischemic stroke] AND [cerebrospinal fluid]". We included only studies written in English, including patients with a primary diagnosis of either ischemic stroke or transient ischemic attack (TIA), and where white blood cell count in the spinal fluid was presented. Studies investigating common etiologies for pleocytosis, was excluded. Study and patient characteristics, white blood cell count and time to lumbar puncture were presented in tables, and the prevalence of pleocytosis were reported and plotted graphically. RESULTS: We included 15 studies with 1607 patients, 1522 with ischemic stroke and 85 with TIA. The prevalence of pleocytosis was between 0% to 28,6% and a mean of 11.8%. The highest white blood cell count found with common etiologies for pleocytosis ruled out was 56 cells/mm3. A mean white blood cell count of 4.0 was based on the three studies where this was available. DISCUSSION: The included studies were methodologically heterogenous and few had pleocytosis as primary outcome. Pleocytosis following ischemic stroke is uncommon and should prompt further investigations.

Depressive symptoms and risk of acute stroke: INTERSTROKE case-control study

METHODS: The INTERSTROKE is an international case-control study of risk factors of first acute stroke, conducted in 32 countries. Cases were patients with CT- or MRI-confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and the use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of prestroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of prestroke depressive symptoms with poststroke functional outcome, measured with the modified Rankin scale at 1 month after stroke. RESULTS: Of 26,877 participants, 40.4% were women, and the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared with that in controls (18.3% vs 14.1%, p < 0.001) and differed by region (p interaction <0.001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses, prestroke depressive symptoms were associated with greater odds of acute stroke (odds ratio [OR] 1.46, 95% CI 1.34-1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95% CI 1.28-1.91) and ischemic stroke (OR 1.44, 95% CI 1.31-1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While preadmission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95% CI 0.94-1.10), they were associated with a greater odds of poor functional outcome at 1 month after acute stroke (OR 1.09, 95% CI 1.01-1.19). DISCUSSION: In this global study, we recorded that depressive symptoms are an important risk factor of acute stroke, including both ischemic and hemorrhagic stroke. Preadmission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in poststroke recovery.

Patient-tailored transcranial direct current stimulation to improve stroke rehabilitation: study protocol of a randomized sham-controlled trial.

BACKGROUND: Many patients do not fully regain motor function after ischemic stroke. Transcranial direct current stimulation (TDCS) targeting the motor cortex may improve motor outcome as an add-on intervention to physical rehabilitation. However, beneficial effects on motor function vary largely among patients within and across TDCS trials. In addition to a large heterogeneity of study designs, this variability may be caused by the fact that TDCS was given as a one-size-fits-all protocol without accounting for anatomical differences between subjects. The efficacy and consistency of TDCS might be improved by a patient-tailored design that ensures precise targeting of a physiologically relevant area with an appropriate current strength. METHODS: In a randomized, double-blinded, sham-controlled trial, patients with subacute ischemic stroke and residual upper-extremity paresis will receive two times 20 min of focal TDCS of ipsilesional primary motor hand area (M1-HAND) during supervised rehabilitation training three times weekly for 4 weeks. Anticipated 60 patients will be randomly assigned to active or sham TDCS of ipsilesional M1-HAND, using a central anode and four equidistant cathodes. The placement of the electrode grid on the scalp and current strength at each cathode will be personalized based on individual electrical field models to induce an electrical current of 0.2 V/m in the cortical target region resulting in current strengths between 1 and 4 mA. Primary endpoint will be the difference in change of Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score between active TDCS and sham at the end of the intervention. Exploratory endpoints will include UE-FMA at 12 weeks. Effects of TDCS on motor network connectivity and interhemispheric inhibition will be assessed with functional MRI and transcranial magnetic stimulation. DISCUSSION: The study will show the feasibility and test the efficacy of personalized, multi-electrode anodal TDCS of M1-HAND in patients with subacute stroke patients with upper-extremity paresis. Concurrent multimodal brain mapping will shed light into the mechanisms of action of therapeutic personalized TDCS of M1-HAND. Together, the results from this trial may inform future personalized TDCS studies in patients with focal neurological deficits after stroke.

Depressive Symptoms and Risk of Acute Stroke: INTERSTROKE Case-Control Study.

BACKGROUND AND OBJECTIVES: Depression has been reported to be a risk factor of acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type. METHODS: The INTERSTROKE is an international case-control study of risk factors of first acute stroke, conducted in 32 countries. Cases were patients with CT- or MRI-confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and the use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of prestroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of prestroke depressive symptoms with poststroke functional outcome, measured with the modified Rankin scale at 1 month after stroke. RESULTS: Of 26,877 participants, 40.4% were women, and the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared with that in controls (18.3% vs 14.1%, p < 0.001) and differed by region (p interaction <0.001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses, prestroke depressive symptoms were associated with greater odds of acute stroke (odds ratio [OR] 1.46, 95% CI 1.34-1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95% CI 1.28-1.91) and ischemic stroke (OR 1.44, 95% CI 1.31-1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While preadmission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95% CI 0.94-1.10), they were associated with a greater odds of poor functional outcome at 1 month after acute stroke (OR 1.09, 95% CI 1.01-1.19). DISCUSSION: In this global study, we recorded that depressive symptoms are an important risk factor of acute stroke, including both ischemic and hemorrhagic stroke. Preadmission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in poststroke recovery.

Processes of Care and Associated Factors in Patients With Stroke by Immigration Status.

BACKGROUND: Receiving evidence-based stroke care processes is associated with good clinical outcome. However, data on early stroke care among immigrants are scarce. OBJECTIVE: We investigated whether guideline-recommended acute stroke care and associated factors differ between immigrants and Danish-born residents. DESIGN: Patients admitted with ischemic and hemorrhagic stroke diagnoses (n=129,724) between 2005 and 2018 were identified from the Danish Stroke Registry. RESULTS: We included 123,928 Danish-born residents and 5796 immigrants with stroke. Compared with Danish-born residents, immigrants were less likely to be admitted to a stroke unit within 24 hours after stroke onset (81.5% vs. 83.9%, P <0.001) and had lower odds of early stroke care including dysphagia screening, physiotherapy, occupational therapy, and nutritional assessment. After adjustment for age, sex, clinical, and sociodemographic factors, immigrants had lower odds of early stroke unit admission (odds ratio [OR]: 0.97; 95% CI, 0.94-0.99), early dysphagia screening (OR: 0.96; 95% CI, 0.93-0.98), early physiotherapy (OR: 0.96; 95% CI, 0.94-0.99), and early occupational therapy (OR: 0.96; 95% CI, 0.93-0.98) than Danish-born residents. Small absolute differences in overall quality of stroke care were found when comparing immigrants and Danish-born residents. Significant factors associated with greater likelihood of stroke care included high income, high education, and cohabitation. CONCLUSIONS: Immigrants had lower chances of early stroke unit admission and received fewer individual early stroke care processes such as dysphagia screening, physiotherapy and occupational therapy than Danish-born residents. However, the absolute disparities were in general minor and largely influenced by socioeconomic status and cohabitation.

Autonomic dysfunction after mild acute ischemic stroke and six months after: a prospective observational cohort study.

INTRODUCTION: Autonomic dysfunction is prevalent in ischemic stroke patients and associated with a worse clinical outcome. We aimed to evaluate autonomic dysfunction over time and the tolerability of the head-up tilt table test in an acute stroke setting to optimize patient care. PATIENTS AND METHOD: In a prospective observational cohort study, patients were consecutively recruited from an acute stroke unit. The patients underwent heart rate and blood pressure analysis during the Valsalva maneuver, deep breathing, active standing, and head-up tilt table test if active standing was tolerated. In addition, heart rate variability and catecholamines were measured. All tests were performed within seven days after index ischemic stroke and repeated at six months follow-up. RESULTS: The cohort was comprised of 91 acute stroke patients, mean (SD) age 66 (11) years, median (IQR) initial National Institute of Health Stroke Scale 2 (1-4) and modified Ranking Scale 2 (1-3). The head-up tilt table test revealed 7 patients (10%) with orthostatic hypotension. The examination was terminated before it was completed in 15%, but none developed neurological symptoms. In the acute state the prevalence of autonomic dysfunction varied between 10-100% depending on the test. No changes were found in presence and severity of autonomic dysfunction over time. CONCLUSION: In this cohort study of patients with mild stroke, autonomic dysfunction was highly prevalent and persisted six months after index stroke. Head-up tilt table test may be used in patients who tolerate active standing. Autonomic dysfunction should be recognized and handled in the early phase after stroke.

Cortical hemodynamic response during cognitive Stroop test in acute stroke patients assessed by fNIRS.

BACKGROUND: Following acute ischemic stroke (AIS) many patients experience cognitive impairment which interferes neurorehabilitation. Understanding and monitoring pathophysiologic processes behind cognitive symptoms requires accessible methods during testing and training. Functional near-infrared spectroscopy (fNIRS) can assess activational hemodynamic responses in the prefrontal cortex (PFC) and feasibly be used as a biomarker to support stroke rehabilitation. OBJECTIVE: Exploring the feasibility of fNIRS as a biomarker during the Stroop Color and Word Test (SCWT) assessing executive function in AIS patients. METHODS: Observational study of 21 patients with mild to moderate AIS and 22 healthy age- and sex-matched controls (HC) examined with fNIRS of PFC during the SCWT. Hemodynamic responses were analyzed with general linear modeling. RESULTS: The SCWT was performed worse by AIS patients than HC. Neither patients nor HC showed PFC activation, but an inverse activational pattern primarily in superolateral and superomedial PFC significantly lower in AIS. Hemodynamic responses were incoherent to test difficulty and performance. No other group differences or lateralization were found. CONCLUSIONS: AIS patients had impaired executive function assessed by the SCWT, while both groups showed an inverse hemodynamic response significantly larger in HC. Investigations assessing the physiology behind inverse hemodynamic responses are warranted before deeming clinical implementation reasonable.

High-intensity training in patients with lacunar stroke: A one-year follow-up.

OBJECTIVES: Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke. MATERIALS AND METHODS: Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke. RESULTS: We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group. CONCLUSIONS: Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.

A Systematic Review of the Circadian Rhythm of Bone Markers in Blood.

There exists a marked circadian variation for several bone markers (BM), which is influenced by endogenous as well as exogenous factors including hormones, physical activity, and fasting. Consequently, was the aim of this review to provide an overview of the knowledge of the circadian variation of BM and which factors influence this rhythmicity. A systematic search of PubMed was performed for studies evaluating the circadian variation of BM and which factors influence this rhythmicity. The studies were screened for eligibility by a set of predetermined criteria including a list of relevant BM and a minimum study duration of 24 h with at least 3 blood samples of which two should be at least 6 h apart. In total were 29 papers included. There exists a marked circadian variation for most BM including Carboxy-terminal Cross-Linked Telopeptide of Type I Collagen (CTX) and osteocalcin (OC) with nighttime or early morning peak. Pro-collagen Type I N-terminal Propeptide (PINP) and PTH also showed circadian rhythm but with less amplitude. The inter-osteoblast-osteoclast regulatory markers such as OPG, RANKL, FGF23, and sclerostin showed no circadian rhythm. The markers were differently affected by exogenous factors like fasting, which greatly reduced the circadian variation of CTX but did not affect PINP or OC. The marked circadian variation and the factors which influence the rhythmicity, e.g., fasting are of great consequence when measuring BM. To reduce variation and heighten validity should circadian variation and fasting be kept in mind when measuring BM.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Capillary transit time heterogeneity inhibits cerebral oxygen metabolism in patients with reduced cerebrovascular reserve capacity from steno-occlusive disease.

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.

An Explorative Investigation of the Effect of Naturalistic Light on Agitation-Associated Behavior in Nursing Home Residents With Dementia: A Pilot Study.

AIM: To study the effect of naturalistic light, programmed to replicate the spectrum distribution of natural light from dusk to dawn, on agitation measured with a Cohen-Mansfield Agitation Inventory-inspired score of nursing home residents with dementia. BACKGROUND: Though the effects of different types of light on the sleep-wake patterns of senior adults and people with dementia have been examined in several studies, the effects of naturalistic light systems, as a possible nonpharmacological intervention to improve sleep and reduce agitation, have yet to be extensively evaluated due to the relative novelty of the technology. METHODS: The study was designed as a 6-month pilot study of a prospective interventional longitudinal cohort study, with five participants recruited from a single department of a Danish nursing home. The effect of naturalistic lighting on agitation-associated behaviors was recorded over a 3-day period pre- and postintervention. Results: An overall 71.2% reduction in the frequency of agitation-associated behaviors was recorded, with the frequency of some behaviors even reduced by 100%. CONCLUSIONS: This pilot study estimates that naturalistic lighting may be a promising nonpharmacological intervention to improve the overall agitation of nursing home residents with dementia, with a possible added benefit of an improved work environment for the staff. This study, therefore, finds indication for the performance of a randomized controlled trial with the same intervention and a larger cohort.

Alcohol Intake as a Risk Factor for Acute Stroke: The INTERSTROKE Study.

BACKGROUND AND OBJECTIVES: There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study. METHODS: INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorized by drinks/week as low (1-7), moderate (7-14 for females and 7-21 for males), or high (>14 for females and >21 for males). Heavy episodic drinking (HED) was defined as >5 drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations. RESULTS: We included 12,913 cases and 12,935 controls; 25.0% (n = 6,449) were current drinkers, 16.7% (n = 4,318) former drinkers, and 58.3% (n = 15,076) never drinkers. Current drinkers were younger, male, smokers, active, and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14; 95% CI 1.04-1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21-1.84) but not ischemic stroke (OR 1.06; 95% CI 0.95-1.19). HED pattern was associated with all stroke (OR 1.39; 95% CI 1.21-1.59), ischemic stroke (OR 1.29; 95% CI 1.10-1.51), and ICH (OR 1.76; 95% CI 1.31-2.36). High level of alcohol intake was consistently associated with all stroke, ischemic stroke, and ICH. Moderate intake was associated with all stroke and ICH but not ischemic stroke. Low alcohol intake was not associated with stroke overall, but there were regional differences; low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66; 95% CI 0.45-0.96) and increased odds in India (OR 2.18; 95% CI 1.42-3.36) (p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers. DISCUSSION: High and moderate intake were associated with increased odds of stroke, whereas low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.