INTERSTROKE Highlights Urgent Need for Stroke Prevention

July 26, 2016

A second study to be reported in a matter of weeks has highlighted the "huge" role of potentially modifiable risk factors in the burden of stroke worldwide.

The INTERSROKE study — which included data on almost 27,000 individuals from 32 countries — shows that 10 potentially modifiable risk factors are collectively associated with about 90% of stroke burden worldwide, highlighting the need for global prevention programs.

But the data also show regional variations in the relative importance of most individual risk factors, suggesting that prevention programs need to be tailored differently in different countries, the authors note.

The INTERSTROKE study was published online in The Lancet on July 15, with senior author Salim Yusuf, MD, from McMaster University, Hamilton, Ontario, Canada.

It follows publication of the Global Burden of Disease (GBD) study last month in The Lancet Neurology, reported by Medscape Medical News at that time, which also analyzed the contribution of modifiable risk factors to the stroke burden worldwide and came up with similar estimates using a different method.

Lead author of the INTERSTROKE trial, Martin J. O'Donnell, MD, from McMaster University, explained to Medscape Medical News that the two studies had similar objectives — to understand which risk factors contributed most toward stroke — but used different approaches to collect this information.

"GBD was essentially a very large meta-analysis of observational studies along with various modeling techniques so it included many different methodologies," he said. "Our study is in effect a massive case-control study, so it was a much more standardized approach across all regions.

"While the two studies showed slightly different results in terms of individual risk factors — which is probably due to different methodologies used and how the risk factors were defined -— they both came to the same general conclusion: that around 90% of stroke burden is caused by risk factors that are potentially modifiable," he added.

Hypertension the Biggest Culprit

Both studies showed that hypertension is by far the greatest contributor to stroke burden in all regions. Dr O'Donnell noted: "Even in Western countries, a large proportion of people are unaware that their blood pressure is not at optional levels. This is the obvious place to start with prevention programs."

He added: "The GBD study may have under-represented low- and middle-income countries as there are fewer studies available from those countries, whereas we purposely included more subjects from low- and middle-income countries as they have not been well studied before and there is a larger stroke burden there. We also requested that the stroke patients involved were scanned so we have information on risk factors for ischemic and hemorrhagic stroke."

Dr O'Donnell also pointed out that the two studies included some different risk factors; for example, GBD included air pollution while INTERSTROKE gathered data on atrial fibrillation.

Dr O'Donnell said he was surprised that the role of these modifiable risk factors was so large. "When we started we thought we would see a high level of stroke burden attributable to these modifiable risk factors, maybe something like 60%, but our results show a 90% contribution — much greater than we anticipated. And while there are variations across regions in terms of individual risk factors, we have been struck by the high contribution of these factors in combination in all worldwide regions.

The big question is how much we can modify these risk factors and, by doing this, how much of the stroke burden can we eliminate? Dr Martin O'Donnell

"The big question is how much we can modify these risk factors and, by doing this, how much of the stroke burden can we eliminate?" he added. "Obviously we are not going to eliminate the whole 90%, but we need to work out what sort of targets we should be aiming for and the best strategies to try and make that happen."

He said the data suggested a two-tier approach may be best: a global program because of the commonality of risk factors but also local programs where more emphasis could be put on different risk factors depending on how much they have been shown to contribute to stroke burden in that particular area.

For example, alcohol consumption had a higher magnitude of association with stroke burden in South Asia and Africa. "This may be due to different patterns of alcohol consumption with more heavy episodic drinking." In contrast, atrial fibrillation (AF) had a higher contribution to stroke burden in North America and other Western countries, "so the benefits of AF screening programs are likely to be greater there."

Study Details

For the study, the researchers gathered data on 13,447 patients with their first acute stroke (10,388 ischemic and 3059 hemorrhagic) within 5 days of symptom onset and 72 hours of hospital admission and 13,472 controls from the same community matched for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples.

Results showed that, collectively, 10 risk factors accounted for 90.7% of the population associated risk (PAR) for all stroke worldwide (91.5% for ischemic stroke and 87.1% for hemorrhagic stroke) 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 or younger and 90.0% in patients older than age 55 years).

Table. INTERACT: Individual Risk Factor Contribution to PAR of Stroke

Risk Factor Odds Ratio for Stroke PAR (%)
History of hypertension or blood pressure ≥140/90 mm Hg 2.98 47.9
Regular physical activity 0.60 35.8
ApoB/ApoA1 ratio 1.84 (highest vs lowest tertile) 26.8 (top 2 tertiles vs lowest tertile)
Diet 0.60 (highest vs lowest tertile of mAHEI) 23.2 (lowest 2 tertiles vs highest tertile of mAHEI)
Waist-to-hip ratio 1.44 (highest vs lowest tertile) 18.6 (top two tertiles vs lowest)
Psychosocial factors 2.20 17.4
Current smoking 1.67 12.4
Cardiac causes 3.17 9.1
Alcohol consumption 2.09 (high or heavy episodic intake vs never-drinker or former drinker) 5.8 (current alcohol drinker vs never-drinker or former drinker)
Diabetes mellitus 1.16 3.9

Apo = apolipoprotein; mAHEI = modified Alternative Healthy Eating Index.


Hypertension was more associated with intracerebral hemorrhage than with ischemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischemic stroke.

One anomaly in the study was the diet risk score, which was developed in the West, so that a higher score signals a reduced risk for stroke, but bizarrely in South Asia the opposite association was found.

"We are trying to understand why this has occurred," Dr O'Donnell commented. "It is probably as a result of different types of foods eaten in South Asia, so we obviously have to be careful about interpreting this particular information in this region. And there probably needs to be a different diet risk score developed for countries which have very different types of foods."

Emergency Action Plan Needed

In an accompanying Comment, Valery L. Feigin, MD, PhD, and Rita Krishnamurthi, PhD, from the National Institute for Stroke and Applied Neurosciences, Auckland, New Zealand, who were involved in the GBD study, say the INTERSTROKE findings reinforce the fact that "stroke is a highly preventable disease globally, irrespective of age and sex."

They add that regional or ethnic-specific primary prevention programmes should now be developed, focusing on risk factors that contribute most to the risk for stroke in that particular region; cost-effectiveness research on primary stroke prevention in key populations is also required.

"It should also be emphasised that stroke prevention programmes must be integrated with prevention of other major non-communicable diseases that share common risk factors with stroke to be cost-effective."

They conclude: "We have heard the calls for actions about primary prevention. Now is the time for governments, health organisations, 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."

INTERSTROKE was funded by the 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 Vastra Gotaland (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.

Lancet. Published online July 15, 2016. Abstract Comment

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