Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study
Martin O’DonnellSiu Lim ChinSumathy RangarajanDenis XavierLisheng LiuHongye ZhangRao PsPrem PaisSteven AgapayPatricio López‐JaramilloAlbertino DamascenoPeter LanghorneMatthew McQueenAnnika RosengrenMahshid DehghanGraeme J. HankeyAntonio L DansAhmed ElSayedÁlvaro AvezumCharles MondoHans‐Christoph DienerDanuta RyglewiczAnna CzłonkowskaNana PogosovaChristian WeimarRomaina IqbalRafael DíazKhalid YusoffAfzalhussein YusufaliAytekin OğuzXingyu WangErnesto PeñaherreraFernando LaņasOkechukwu S. OgahAdesola OgunniyiHelle K. IversenGermán MálagaZvonko RumboldtShahram OveisgharanF HussainDaliwonga MagaziYongchai NilanontJohn FergusonGuillaume ParéSalim Yusuf
Key result
Ten modifiable risk factors account for ~91% of global stroke risk.
- PAR 90.7%
- n=26,919
Why the study?
Stroke is a leading cause of death and disability worldwide, especially in low-income and middle-income countries, but the importance of modifiable risk factors across regions and stroke subtypes was not quantified.
What is the population attributable risk of potentially modifiable risk factors for acute stroke globally and across different regions?
Key Points
- Quantify the global and regional contributions of potentially modifiable risk factors to acute first stroke across diverse populations and stroke subtypes.
- Standardized international case-control study conducted across 32 countries between 2007 and 2015, enrolling N=26,919 participants (13,447 acute first stroke cases and 13,472 age- and sex-matched controls).
- Stroke cases (10,388 ischaemic strokes and 3,059 intracerebral haemorrhages) were evaluated within 5 days of symptom onset and 72 hours of hospital admission alongside clinical and laboratory evaluations.
- Ten modifiable risk factors collectively accounted for 90.7% of the population attributable risk (PAR) for all strokes worldwide (91.5% for ischaemic stroke, 87.1% for intracerebral haemorrhage).
- Hypertension was the strongest factor (OR 2.98, 99% CI 2.72–3.28; PAR 47.9%, 99% CI 45.1–50.6), alongside physical inactivity (PAR 35.8%), elevated ApoB/ApoA1 ratio (PAR 26.8%), poor diet (PAR 23.2%), and abdominal obesity (PAR 18.6%).
- Hypertension correlated more strongly with intracerebral haemorrhage than ischaemic stroke, whereas smoking, diabetes, apolipoproteins, and cardiac causes were more strongly associated with ischaemic stroke (p<0.0001).
Study Design
Type
Case-Control (n=26,919)
Multicenter
Yes
Structured PICO
What is the population attributable risk of potentially modifiable risk factors for acute stroke globally and across different regions?
P
Population
26,919 participants from 32 countries, comprising 13,447 cases of acute first stroke and 13,472 age- and sex-matched controls without stroke.
E
Exposure
Ten potentially modifiable risk factors (hypertension, physical activity, apolipoprotein B/ApoA1 ratio, diet, waist-to-hip ratio, psychosocial factors, current smoking, cardiac causes, alcohol consumption, and diabetes mellitus)
C
Comparator
Hospital-based or community-based control individuals with no history of stroke
O
Outcome
Acute first stroke (ischaemic or intracerebral haemorrhage)hard clinical
Main Result
Effect estimate: PAR 90.7%
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“INTERSTROKE demonstrates that the majority of stroke is due to common modifiable risk factors. Our findings will inform the development of global population-level interventions to reduce stroke, and how such programmes may be tailored to individual regions, as we did observe some regional differences in the importance of some risk factors by region. This includes better health education, more affordable healthy food, avoidance of tobacco and more affordable medication for hypertension and dyslipidaemia.”
MOMartin O'DonnellProfessor of translational medicine, NUI Galway
“Clearly the most important risk factor is hypertension, which is something that's enormously modifiable through lifestyle and generic inexpensive medications. When you consider its contribution not just to stroke but to cardiovascular disease in general [and] its contribution to dementia, it is quite remarkable that we don't have better... availability of blood pressure screening and better availability of inexpensive therapies to treat it.”
MOMartin O'DonnellProfessor of translational medicine, NUI Galway
“We have confirmed the ten modifiable risk factors associated with 90% of stroke cases in all regions, young and older and in men and women. The study also confirms that hypertension is the most important modifiable risk factor in all regions, and the key target in reducing the burden of stroke globally.”
Implication
Ten potentially modifiable risk factors account for approximately 90% of the population attributable risk of stroke globally, highlighting the massive potential for global and regional stroke prevention programs.
Abstract
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.
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Cite This Study
O'Donnell et al. (2016) conducted a case-control in acute stroke (n=26,919). Ten potentially modifiable risk factors vs. Absence of risk factors / Matched controls was evaluated on All stroke (PAR 90.7%). Ten potentially modifiable risk factors were collectively associated with 90.7% of the population attributable risk for all stroke worldwide.