Elsevier

The Lancet

Volume 376, Issue 9735, 10–16 July 2010, Pages 112-123
The Lancet

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Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study

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Summary

Background

The contribution of various risk factors to the burden of stroke worldwide is unknown, particularly in countries of low and middle income. We aimed to establish the association of known and emerging risk factors with stroke and its primary subtypes, assess the contribution of these risk factors to the burden of stroke, and explore the differences between risk factors for stroke and myocardial infarction.

Methods

We undertook a standardised case-control study in 22 countries worldwide between March 1, 2007, and April 23, 2010. Cases were patients with acute first stroke (within 5 days of symptoms onset and 72 h of hospital admission). Controls had no history of stroke, and were matched with cases for age and sex. All participants completed a structured questionnaire and a physical examination, and most provided blood and urine samples. We calculated odds ratios (ORs) and population-attributable risks (PARs) for the association of all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke with selected risk factors.

Findings

In the first 3000 cases (n=2337, 78%, with ischaemic stroke; n=663, 22%, with intracerebral haemorrhagic stroke) and 3000 controls, significant risk factors for all stroke were: history of hypertension (OR 2·64, 99% CI 2·26–3·08; PAR 34·6%, 99% CI 30·4–39·1); current smoking (2·09, 1·75–2·51; 18·9%, 15·3–23·1); waist-to-hip ratio (1·65, 1·36–1·99 for highest vs lowest tertile; 26·5%, 18·8–36·0); diet risk score (1·35, 1·11–1·64 for highest vs lowest tertile; 18·8%, 11·2–29·7); regular physical activity (0·69, 0·53–0·90; 28·5%, 14·5–48·5); diabetes mellitus (1·36, 1·10–1·68; 5·0%, 2·6–9·5); alcohol intake (1·51, 1·18–1·92 for more than 30 drinks per month or binge drinking; 3·8%, 0·9–14·4); psychosocial stress (1·30, 1·06–1·60; 4·6%, 2·1–9·6) and depression (1·35, 1·10–1·66; 5·2%, 2·7–9·8); cardiac causes (2·38, 1·77–3·20; 6·7%, 4·8–9·1); and ratio of apolipoproteins B to A1 (1·89, 1·49–2·40 for highest vs lowest tertile; 24·9%, 15·7–37·1). Collectively, these risk factors accounted for 88·1% (99% CI 82·3–92·2) of the PAR for all stroke. When an alternate definition of hypertension was used (history of hypertension or blood pressure >160/90 mm Hg), the combined PAR was 90·3% (85·3–93·7) for all stroke. These risk factors were all significant for ischaemic stroke, whereas hypertension, smoking, waist-to-hip ratio, diet, and alcohol intake were significant risk factors for intracerebral haemorrhagic stroke.

Interpretation

Our findings suggest that ten risk factors are associated with 90% of the risk of stroke. Targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the burden of stroke.

Funding

Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Pfizer Cardiovascular Award, Merck, AstraZeneca, and Boehringer Ingelheim.

Introduction

Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions.1, 2 Countries of low and middle income have the largest burden of stroke, accounting for more than 85% of stroke mortality worldwide, but few reliable data are available to identify risk factors for stroke in most of these regions, and particularly for haemorrhagic stroke.1, 2, 3, 4, 5

Findings from the INTERHEART study6, 7, 8, 9, 10 suggested that nine modifiable risk factors explain most of the risk of myocardial infarction worldwide. An equivalent study is needed for stroke because stroke has several pathologies other than large artery atherosclerosis,11 so risk factors for stroke and its aetiological subtypes could differ from those for myocardial infarction. Furthermore, the independent contribution of each risk factor to the burden of stroke worldwide—the population-attributable risk (PAR)—is unknown in most regions.

The INTERHEART study showed the feasibility, value, and importance of a large standardised international case-control study (29 972 participants) to establish the importance of, and relation between, key risk factors for myocardial infarction in 52 countries of high, middle, and low income, with participation from every inhabited continent.6, 7, 8, 9, 10 However, additional challenges are presented by a similar study for stroke. In particular, routine neuroimaging is needed to establish primary stroke subtypes (ischaemic vs haemorrhagic), and patients with disabling stroke who are unable to communicate need to be represented in the study.

The INTERSTROKE study is an international, multicentre, case-control study, designed to establish the association of traditional and emerging risk factors with stroke (and primary stroke subtypes) in countries of high, middle, and low income. We report the results of phase 1 of 3000 cases and 3000 controls from 22 countries, showing that an international case-control study is feasible for stroke, and provide estimates of the importance of common risk factors. Phase 2 is underway and is expected to be completed in the next 3 years.

Section snippets

Participants

The design of the INTERSTROKE study has been reported previously,12 and we provide a brief summary. Participants were recruited from 84 centres in 22 countries: Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Croatia, Denmark, Ecuador, Germany, India, Iran, Malaysia, Mozambique, Nigeria, Peru, Philippines, Poland, South Africa, Sudan, and Uganda. Phase 1 lasted from March 1, 2007, to April 23, 2010.

Cases were admitted to hospital with first acute stroke, defined as “a clinical

Results

A screening log was maintained for about 3 months in 42 centres from 14 countries. Of 5668 patients in the screening log, 762 (13%) were eligible to be included in phase 1. The most common reasons for ineligibility were: patient had had a previous stroke (n=1199, 24%); stroke did not meet the clinical definition (n=871, 18%); time window for symptom duration was exceeded (n=1294, 26%); and patient was unable to communicate because of severe stroke, aphasia, or dementia, and did not have a valid

Discussion

The INTERSTROKE study is the first large standardised case-control study of risk factors for stroke in which countries of low and middle income were included, and all cases completed routine neuroimaging. Our findings showed that five risk factors accounted for more than 80% of the global risk of all stroke (ischaemic and intracerebral haemorrhagic): hypertension, current smoking, abdominal obesity, diet, and physical activity. With the addition of five other risk factors, including

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