Vast Majority of Strokes Caused by Potentially Modifiable Factors

Combined, 10 modifiable risk factors account for about nine out of every 10 strokes that occur across the globe, according to findings from an expanded phase of the INTERSTROKE study.

Hypertension, which leads the way in terms of attributable risk, is joined by smoking, diabetes, low physical activity, poor diet, psychosocial factors, abdominal obesity, alcohol use, cardiac causes, and adverse levels of apolipoproteins on the list of risk factors, Martin O’Donnell, MB, PhD (McMaster University, Hamilton, Canada), and colleagues report in a study published online July 15, 2016, ahead of print in the Lancet.

The consistency of the combined contribution of the 10 factors to stroke risk across various regions was surprising, because prior research had suggested that only 50% to 60% of strokes could be attributed to these variables in some areas, O’Donnell told TCTMD.

“In some ways, this is positive news in that we can quantify so much of the modifiable risk,” he said.

“Clearly the most important risk factor is hypertension, which is something that’s enormously modifiable through lifestyle and generic inexpensive medications,” he continued, adding that there is a need for greater uptake of screening. “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.”

Some Surprises

The 10 risk factors identified in this analysis are consistent with what was found in the first phase of INTERSTROKE, which included 6,000 patients. The expanded second phase, which included 13,447 patients with stroke (77.3% ischemic) and 13,472 controls with no history of stroke recruited from 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa, was designed to explore variations across regions and various subgroups.

When combined, the variables identified in INTERSTROKE accounted for 90.7% of all strokes, including 91.5% of ischemic strokes and 87.1% of intracerebral hemorrhages. Those figures were consistent across regions, sexes, and age groups. There were, however, some noteworthy variations found when delving deeper into the individual factors, O’Donnell said.

As expected, poor diet—measured using the modified Alternative Healthy Eating Index—was tied to elevated stroke risk in most regions. But there was no relationship between diet and stroke risk in Africa and an association between higher (healthier) scores and greater stroke risk in South Asia.

That “raises some caution . . . that some of these scores may not be applicable in some regions of the world,” O’Donnell said, noting that most diet scores have been developed and validated in Europe and North America. The discrepancy could be related to types and amounts of fruits, vegetables, and other foods that are consumed as well as to differences in food preparation, he added.

There were also variations in the importance of A-fib and hypertension across regions. For hypertension, the association with stroke risk tended to grow stronger in moderate- and lower-income countries.

“What we suspect is happening there is that we’re probably getting a variation in screening and uptake of antihypertensive therapies, but there may actually be ethnic variations in the magnitude of association,” O’Donnell said.

“Despite these differences,” he and his colleagues write in their paper, “the collective contribution of these 10 risk factors to stroke risk was consistent in all populations, meaning that general approaches to prevention of stroke can be similar worldwide, but population-specific refinement of programs might be needed.”

Call to Action

In an accompanying editorial, Valery Feigin, MD, and Rita Krishnamurthi, PhD (Auckland University of Technology, New Zealand), say that three key messages can be taken from the study.

“First, stroke is a highly preventable disease globally, irrespective of age and sex,” they write.

Second, regional variations in the relative importance of risk factors “necessitates the development of regional or ethnic-specific primary prevention programs, including priority settings such as focusing on risk factors contributing most to the risk of stroke in a particular region,” they continue.

And finally, they say, there is a need for more cost-effectiveness analyses and research on countries and ethnic groups that were not included in INTERSTROKE.

The key issues that need to be addressed now are how best to implement primary prevention strategies in practice and how to fund them, according to Feigin and Krishnamurthi.

“We have heard the calls for actions about primary prevention,” they say. “Now is the time for governments, health organizations, and individuals to proactively reduce the global burden of stroke. Governments of all countries should develop and implement an emergency action plan for the primary prevention of stroke.”





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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • O’Donnell MJ, Chin SL, Rangarajan S, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016;Epub ahead of print.

  • Feigin VL, Krishnamurthi R. Stroke is largely preventable across the globe: where to next? Lancet. 2016;Epub ahead of print.

  • The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, the Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, Chest, Heart and Stroke Scotland, and the Stroke Association, with support from the UK Stroke Research Network. The Department of Neurology at the University Duisburg-Essen received research grants from the German Research Council (DFG), German Ministry of Education and Research (BMBF), European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz-Nixdorf Foundation.
  • O’Donnell reports no relevant conflicts of interest.