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 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.

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.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12342 (92%) of 13447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However, across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14­1·44; all p< 0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12­1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: DataFrom ROCKET AF

Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factorsfor all-cause mortality may guide interventions. Methods and Results-—In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identifiedfactors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intentionto-treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up,1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C-index 0.677). Conclusions-—In a large population of patients anticoagulated for nonvalvular atrial fibrillation, 7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival...

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifi able risk factors for stroke in diff erent regions of the world,and in key populations and primary pathological subtypes of stroke. Methods We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute fi rst stroke (within 5 days of symptom onset and72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke,and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks(PARs) were calculated, with 99% confi dence intervals...

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery

BACKGROUND Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVE To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. METHODS Search methods: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. Selection criteria: We included randomized controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, ...