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| INTERSTROKE | |
|---|---|
| Name | INTERSTROKE |
| Type | Observational study |
| Field | Stroke epidemiology |
| Start date | 2007 |
| End date | 2013 |
| Principal investigators | P. M. Rothwell, S. Yusuf, M. O'Donnell |
| Locations | Multinational (over 22 countries) |
| Sample size | ~27,000 (case-control sample subset ~3,000) |
| Published | 2010–2016 |
INTERSTROKE INTERSTROKE was a large multinational case-control study that quantified the contribution of potentially modifiable risk factors to acute stroke across diverse global populations. It provided comparative estimates of population attributable risk for ischemic stroke and intracerebral hemorrhage, informing international prevention priorities. The study linked clinical phenotypes with standardized risk assessments across sites in multiple continents.
INTERSTROKE arose in the context of rising attention to noncommunicable diseases and global health disparities, following initiatives such as the World Health Organization's Global Burden of Disease collaborations and the United Nations Non-Communicable Diseases agenda. It was conceived by investigators affiliated with institutions including McMaster University, Population Health Research Institute, University of Oxford, and McGill University and built upon prior work like the Framingham Heart Study and the MONICA Project. The study sought to extend evidence from cohort studies such as the Nurses' Health Study and randomized trials like the PROGRESS trial into heterogeneous low-, middle-, and high-income country settings.
INTERSTROKE used a matched case-control design adapted for multicenter international implementation, influenced by methodological frameworks from the WHO MONICA Project and analytics used in the Global Burden of Disease consortium. Standardized case definitions drew on criteria from the American Heart Association and the World Health Organization stroke definitions. Diagnostic verification incorporated neuroimaging interpreted with protocols informed by the European Stroke Organisation recommendations and harmonized data collection instruments borrowed from instruments used in the Atherosclerosis Risk in Communities Study.
Cases were adults with first-ever or recurrent acute stroke enrolled at participating hospitals and centers in regions spanning North America, South America, Europe, Africa, Asia, and Oceania. Controls were hospital or community-based and matched on age and sex in most sites, with sampling strategies referencing designs used by the INTERHEART study. Data collection combined structured interviews, physical measurements, and laboratory sampling; measurements paralleled standards from the Clinical Trials Unit frameworks at institutions like University of Toronto and Johns Hopkins University. Neuroimaging confirmation employed scanners and protocols consistent with practice at centers such as Massachusetts General Hospital and Karolinska Institutet.
INTERSTROKE reported that a limited set of potentially modifiable risk factors accounted for the majority of global stroke risk, echoing findings from cardiovascular research exemplified by studies like INTERHEART. The study estimated that hypertension, smoking, waist-to-hip ratio, diet, physical activity, diabetes, alcohol intake, psychosocial factors, cardiac causes (including atrial fibrillation), and lipids together explained a large fraction of stroke risk across regions. Regional variations mirrored patterns observed in epidemiological work from China Medical University, University of São Paulo, and Tata Memorial Centre cohorts, with differences in hemorrhagic versus ischemic stroke proportions similar to reports from Oxford Vascular Study and Shanghai Stroke Registry.
INTERSTROKE identified key modifiable risk factors: raised blood pressure (hypertension), current smoking, abdominal obesity measured as waist-to-hip ratio, lack of regular physical activity, poor diet (low fruit and vegetable intake), diabetes mellitus, high alcohol consumption, psychosocial stress and depression, cardiac causes including atrial fibrillation, and abnormal lipid profiles. These risk factors were comparable to those highlighted in the Framingham Heart Study and the Global Registry of Acute Coronary Events but emphasized anthropometric and behavioral drivers relevant across India, South Africa, Russia, and Mexico sites.
Analyses used conditional logistic regression for matched case-control data, calculation of population attributable risks, and sensitivity analyses for unmeasured confounding, paralleling approaches in meta-analyses by groups at Harvard School of Public Health and statistical methods from the Cochrane Collaboration. The study reported adjustments for socioeconomic and demographic covariates modeled similarly to work from the World Bank population health analyses. Internal validity was supported by standardized protocols and centralized training akin to multicenter trials run by the International Stroke Trial investigators; external validity benefitted from geographic diversity, though heterogeneity across sites was formally tested with stratified analyses and interaction terms.
INTERSTROKE influenced policy discussions in organizations such as the World Health Organization and national public health agencies in Canada, United Kingdom, and Australia by prioritizing hypertension control, tobacco cessation, and obesity reduction. The results were cited in guideline deliberations by the American Heart Association/American Stroke Association, informed public health targets aligned with the UN Sustainable Development Goals, and motivated implementation research in programs at institutions like Bangladesh Institute of Research and Rehabilitation and Ghana Health Service.
Critiques of INTERSTROKE included concerns about case-control susceptibility to selection and recall bias familiar from methodological critiques in the British Medical Journal and commentary in The Lancet. Heterogeneity of control selection and variable availability of neuroimaging at some sites were contrasted with cohort standards seen in the Nurses' Health Study and randomized designs like SPARCL trial. Observational design limited causal inference relative to randomized trials such as HOPE and instrument-based approaches used in Mendelian randomization studies at University of Cambridge. Nonetheless, defenders noted the pragmatic value of global case-control evidence for setting prevention priorities.
Category:Stroke research studies