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.

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.

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...

Validation and comparison of three formulae to estimate sodiumand potassiumexcretion froma singlemorning fasting urine comparedto 24-hmeasures in 11countries

Background and objectives: Although 24-h urinarymeasure to estimate sodium and potassium excretion isthe gold standard, it is not practical for large studies. Wecompared estimates of 24-h sodium and potassiumexcretion from a single morning fasting urine (MFU) usingthree different formulae in healthy individuals.Methods: We studied 1083 individuals aged 35–70 yearsfrom the general population in 11 countries. A 24-h urineand MFU specimen were obtained from each individual. Asubset of 448 individuals repeated the measures after 30–90 days. The Kawasaki, Tanaka, and INTERSALT formulaewere used to estimate urinary excretion from a MFU specimen.Results: The intraclass correlation coefficient (ICC)between estimated and measured sodium excretion washigher with Kawasaki (0.71; 95% confidence interval, CI:0.65–0.76) compared with INTERSALT (0.49; 95% CI:0.29–0.62) and Tanaka (0.54; 95% CI: 0.42–0.62)formulae (P<0.001). For potassium, the ICC was higherwith the Kawasaki (0.55; 95% CI: 0.31–0.69) than theTanaka (0.36; 95% CI: 0.07 to 0.60; P<0.05) formula(no INTERSALT formula exists for potassium). The degreeof bias (vs. the 24-h urine) for sodium was smaller withKawasaki (R313 mg/day; 95% CI: R182 to R444)compared with INTERSALT ( 872 mg/day; 95% CI: 728to 1016) and Tanaka ( 548 mg/day; 95% CI: 408 to 688) formulae (P<0.001 and P»0.02, respectively).Similarly for potassium, the Kawasaki formula provided thebest agreement and least bias. Blood pressure correlatedmost closely and similarly with the 24-h and Kawasakiestimates for sodium compared with the other twoformulae.Conclusion: In a diverse population, the Kawasaki formulais the most valid and least biased method of estimating24-h sodium excretion from a single MFU and is suitablefor population studies.

Association of urinary sodium and potassium excretion with blood pressure

Higher levels of sodium intake are reported to be associated with higher bloodpressure. Whether this relationship varies according to levels of sodium or potassiumintake and in different populations is unknown.MethodsWe studied 102,216 adults from 18 countries. Estimates of 24-hour sodium andpotassium excretion were made from a single fasting morning urine specimen andwere used as surrogates for intake. We assessed the relationship between electrolyteexcretion and blood pressure, as measured with an automated device.ResultsRegression analyses showed increments of 2.11 mm Hg in systolic blood pressureand 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimatedsodium excretion. The slope of this association was steeper with higher sodiumintake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodiumexcretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hgper gram for 55 years of age, 2.43 mm Hg pergram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age;P<0.001 for interaction). Potassium excretion was inversely associated with systolicblood pressure, with a steeper slope of association for persons with hypertensionthan for those without it (P<0.001) and a steeper slope with increased age (P<0.001).ConclusionsIn this study, the association of estimated intake of sodium and potassium, as determinedfrom measurements of excretion of these cations, with blood pressurewas nonlinear and was most pronounced in persons consuming high-sodium diets,persons with hypertension, and older persons. (Funded by the Heart and StrokeFoundation of Ontario and others).