Elsevier

The Lancet

Volume 388, Issue 10046, 20–26 August 2016, Pages 761-775
The Lancet

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

https://doi.org/10.1016/S0140-6736(16)30506-2Get rights and content

Summary

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.

Introduction

Stroke is a leading cause of death and disability, making the prevention of stroke a global health priority.1, 2 In the first phase of the INTERSTROKE study3 (n=6000, 22 countries), ten common, potentially modifiable risk factors were associated with 90% of the population attributable risk (PAR) of acute ischaemic stroke and intracerebral haemorrhage. Although phase 1 of the study provided new information about the composite attributable risk of key risk factors in an international population, the population size was insufficient to reliably describe regional variations in the effect of risk factors, variations within key populations (eg, age, sex), and whether these risk factors varied in their effect on stroke pathological subtypes (ischaemic and haemorrhage stroke).4

Detailed assessment of the importance of risk factors within regions of the world is necessary to find out whether approaches to stroke prevention should differ by region or population characteristic (eg, age, sex, and ethnic origin),4, 5 and whether variations in the importance of risk factors might explain the marked worldwide variations observed in incidence and subtypes of stroke.6 The Global Burden of Disease systematic analysis has reported modelled estimates of the contribution of potentially modifiable risk factors to the global and regional burden of stroke.7, 8 However, estimates are derived from studies of differing methods, with variable use of neuroimaging to establish primary stroke subtype, and under-representation of populations in low-income countries and middle-income countries, where the burden of stroke is largest.6, 9

The aim of the second phase of the INTERSTROKE study was to increase and broaden the sample size to more than 13 000 cases of acute stroke and 13 000 controls in 32 countries to test the hypothesis that variations exist in the effect of common risk factors for stroke by major regions of the world, in key populations (eg, ethnic origin, age, sex), and in subtypes of stroke.

Section snippets

Study design and participants

INTERSTROKE is a large, international case-control study.10 Participants were recruited between Jan 11, 2007, and Aug 8, 2015, from 142 centres in 32 countries in Asia (China, India, Pakistan, Philippines, Thailand, and Malaysia), Africa (Mozambique, Nigeria, South Africa, Sudan, and Uganda), Europe (Croatia, Denmark, Germany, Poland, Russia, Sweden, the UK, Ireland, and Turkey), the Middle East (Iran, Saudi Arabia, Kuwait, and United Arab Emirates), North America (Canada), Australia, and South

Results

26 919 participants were recruited from 32 countries from Jan 11, 2007, to Aug 8, 2015, comprising 13 447 cases of acute first-ever stroke and 13 472 controls (403 [3·0%] of controls had chronic bronchitis, 948 [7·0%] had malaria, 263 [2·0%] had tuberculosis, 127 [0·9%] had venous thrombosis, and 107 [0·8%] had peripheral vascular disease; appendix p 14). Neuroimaging was completed in 13 441 (99·9%) of 13 447 cases. Questionnaires were completed by patients (5573 [41·4%]), proxy respondents

Discussion

In the first phase of the INTERSTROKE study (n=6000),3 we reported preliminary estimates of the association of common risk factors with the PAR for stroke in an international population, but phase 1 was of insufficient scope to report estimates by regions or in key populations. In this full-scale study (which includes phases 1 and 2 of the INTERSTROKE study), we provide more robust and reliable estimates for the contribution of these ten potentially modifiable risk factors in a larger

References (48)

  • NR Poulter et al.

    Hypertension

    Lancet

    (2015)
  • MJ McQueen et al.

    Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study

    Lancet

    (2008)
  • VL Feigin et al.

    Atlas of the Global Burden of Stroke (1990–2013): the GBD 2013 Study

    Neuroepidemiology

    (2015)
  • B Norrving et al.

    Stroke prevention worldwide-what could make it work?

    Neuroepidemiology

    (2015)
  • VL Feigin et al.

    New strategy to reduce the global burden of stroke

    Stroke

    (2015)
  • VL Feigin et al.

    Update on the global burden of ischemic and hemorrhagic stroke in 1990–2013: the GBD 2013 Study

    Neuroepidemiology

    (2015)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

    Lancet

    (2015)
  • VL Feigin et al.

    Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

    Lancet Neurol

    (2016)
  • S Yusuf et al.

    Documenting the global burden of cardiovascular disease: a major achievement but still a work in progress

    Circulation

    (2014)
  • M O'Donnell et al.

    Rationale and design of INTERSTROKE: a global case-control study of risk factors for stroke

    Neuroepidemiology

    (2010)
  • S Hatano

    Experience from a multicentre stroke register: a preliminary report

    Bull World Health Organ

    (1976)
  • R Bonita et al.

    Recovery of motor function after stroke

    Stroke

    (1988)
  • M Dehghan et al.

    Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries

    Circulation

    (2012)
  • J Benichou et al.

    Variance calculations and confidence intervals for estimates of the attributable risk based on logistic models

    Biometrics

    (1990)
  • Cited by (1333)

    • Radiation-Induced Cerebral Contrast Enhancements Strongly Share Ischemic Stroke Risk Factors

      2024, International Journal of Radiation Oncology Biology Physics
    • Sex and stroke risk factors: A review of differences and impact

      2024, Journal of Stroke and Cerebrovascular Diseases
    View all citing articles on Scopus

    See appendix for a full list of study investigators

    View full text