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Lancet. 2016 Aug 20;388(10046):761-75. doi: 10.1016/S0140-6736(16)30506-2. Epub 2016 Jul 16.

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

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Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; Health Research Board Clinical Research Facility, Department of Medicine, NUI Galway, Galway, Ireland. Electronic address:
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
St John's Medical College and Research Institute, Bangalore, India.
National Center of Cardiovascular Disease, Beijing, China.
Beijing Hypertension League Institute, Beijing, China.
Instituto de Investigaciones FOSCAL, Escuela de Medicina, Universidad de Santander, Bucaramanga, Colombia.
Eduardo Mondlane University, Maputo, Mozambique.
Academic Section of Geriatric Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK.
Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.
College of Medicine, University of Philippines, Manila, Philippines.
Alzaeim Alazhari University, Khartoum North, Sudan.
Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
Uganda Heart Institute, Mulago Hospital, Kampala, Uganda.
Department of Neurology, University Hospital, Essen, Germany.
Institute of Psychiatry and Neurology, Warsaw, Poland.
National Research Center for Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
Department of Medicine, Aga Khan University, Karachi, Pakistan.
Estudios Clinicos Latinoamerica, Rosario, Argentina.
Universiti Teknologi MARA, Selayang, Selangor, Malaysia; UCSI University, Cheras, Kuala Lumpur, Malaysia.
Dubai Health Authority, Dubai Medical College, Dubai, United Arab Emirates.
Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
Department of Cardiology, Hospital Luis Vernaza, Guayaquil, Ecuador.
Faculty of Medicine, Universidad de La Frontera, Temuco, Chile.
Division of Cardiovascular Medicine, Department of Medicine, University College Hospital, Ibadan, Nigeria.
Stroke Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
Universidad Peruana Cayetano Heredia, Lima, Peru.
Department of Medicine, University of Split, Split, Croatia.
Rush Alzheimer Disease Research Center, Rush University Medical Center, Chicago, IL, USA.
King Saud University, Riyadh, Saudi Arabia.
Department of Medicine, University of Limpopo, Pretoria, South Africa.
Neurology Division, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Health Research Board Clinical Research Facility, Department of Medicine, NUI Galway, Galway, Ireland.



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.


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.


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).


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.


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.

[Indexed for MEDLINE]

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