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  1. Mente A, O'Donnell MJ, Dagenais G, Wielgosz A, Lear SA, McQueen MJ, et al.
    J Hypertens, 2014 May;32(5):1005-14; discussion 1015.
    PMID: 24569420 DOI: 10.1097/HJH.0000000000000122
    Although 24-h urinary measure to estimate sodium and potassium excretion is the gold standard, it is not practical for large studies. We compared estimates of 24-h sodium and potassium excretion from a single morning fasting urine (MFU) using three different formulae in healthy individuals.
  2. Langhorne P, O'Donnell MJ, Chin SL, Zhang H, Xavier D, Avezum A, et al.
    Lancet, 2018 05 19;391(10134):2019-2027.
    PMID: 29864018 DOI: 10.1016/S0140-6736(18)30802-X
    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 13 447 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 12 342 (92%) of 13 447 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 1·14-1·44; 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; 1·12-1·72) 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.

    FUNDING: Chest, Heart and Stroke Scotland.

  3. Judge C, O'Donnell MJ, Hankey GJ, Rangarajan S, Chin SL, Rao-Melacini P, et al.
    Am J Hypertens, 2021 04 20;34(4):414-425.
    PMID: 33197265 DOI: 10.1093/ajh/hpaa176
    BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke.

    METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.

    RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke.

    CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

  4. O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al.
    Lancet, 2016 Aug 20;388(10046):761-75.
    PMID: 27431356 DOI: 10.1016/S0140-6736(16)30506-2
    BACKGROUND: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 modifiable risk factors for stroke in different 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 first stroke (within 5 days of symptom onset and 72 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% confidence intervals.
    FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).
    INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.
    FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
  5. Wang X, Liu X, O'Donnell MJ, McQueen M, Sniderman A, Pare G, et al.
    EClinicalMedicine, 2024 Apr;70:102515.
    PMID: 38516107 DOI: 10.1016/j.eclinm.2024.102515
    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.

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