Major Finding: Ten factors that were found to be associated with stroke risk were self-reported hypertension, current smoking, abdominal obesity, diet, regular physical activity, diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1.

Data Source: Phase I of INTERSTROKE, a large, multinational, case-control study of 3,000 patients and 3,000 controls.

Disclosures: This study was funded with unrestricted grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Networks, Pfizer Cardiovascular Award, Merck & Co., AstraZeneca, and Boehringer Ingelheim. Multiple authors reported receiving grant/research support, honoraria, expenses, and/or fees from numerous pharmaceutical companies (including those also listed as funding sources for this study), and from other sources, and/or being associated with the American Heart Association as a board member and officer.

Ten distinct risk factors account for about 90% of global stroke risk, according to findings from the first phase of INTERSTROKE, a multinational, case-control study that has enrolled 6,000 patients and controls thus far.

The findings, which suggest that the stroke burden could be substantially reduced by targeted interventions to address the identified risk factors, were published online in the Lancet, and were reported simultaneously at the World Congress of Cardiology in Beijing.

Five of the risk factors that were found to be significantly associated with stroke risk accounted for about 80% of the population-attributable risk for all stroke; these were self-reported hypertension, current smoking, abdominal obesity (highest vs. lowest tertile of waist:hip ratio), diet (highest vs. lowest diet risk score), and regular physical activity. These comparisons yielded odds ratios of 2.64, 2.09, 1.65, 1.35, and 0.69, respectively.

The addition of another five significant risk factors that were identified in this study further increased the population-attributable risk for all stroke associated with these risk factors to 90%. These additional risk factors (diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1) generally increased the odds of stroke by a smaller amount than did the other five risk factors that accounted for a greater proportion of the population-attributable risk. The comparisons yielded odds ratios of 1.36, 1.51, 1.30/1.35, 2.38, and 1.89, respectively.

All risk factors identified in this study were significantly associated with ischemic stroke, whereas hypertension, smoking, waist:hip ratio, diet, and alcohol intake also were significantly associated with intracerebral hemorrhagic stroke, Dr. Martin J. O'Donnell of McMaster University, Hamilton, Ont., and his colleagues reported (Lancet 2010 June 18 [doi:10.1016/S0140-6736(10)60834-3

In an effort to establish the association of conventional and emerging risk factors with stroke, the INTERSTROKE researchers set out to perform a study similar to the INTERHEART study published in 2004, which identified nine modifiable risk factors that explained the majority of myocardial infarctions worldwide.

Between March 1, 2007, and April 23, 2010, the investigators studied 3,000 patients from 22 countries, and 3,000 sex- and age-matched controls with no stroke history. Case patients (2,337 with ischemic stroke and 663 with intracerebral hemorrhagic stroke) presented with acute first stroke, and were enrolled within 5 days of symptom onset and 72 hours of hospital admission. A structured questionnaire and physical examination, including routine neuroimaging, were performed in all patients.

“Our study provides essential information on the importance of common, potentially modifiable vascular risk factors, and builds on previous epidemiological studies,” they wrote, noting that although the risk factors are similar to those identified as being associated with MI in INTERHEART, hypertension, apolipoproteins, physical activity, and alcohol intake appear to have different relative importance for stroke vs. myocardial infarction.

“These findings are important to help guide optimum selection of risk-factor targets for population-based programs to prevent all cardiovascular diseases,” they concluded.

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Data May Spur Prevention Strategies

Stroke is the second-leading cause of death globally, and the cause of more than 85% of deaths in developing countries. Therefore, research on risk factors for stroke around the world is imperative for addressing the problem.

The INTERSTROKE investigators confirmed that hypertension is the leading risk factor for stroke not only in high-income countries, but also in developing countries.

This finding is especially relevant because it highlights the need for regional health authorities to develop strategies to screen the general population for high blood pressure and offer affordable treatment to reduce the burden of stroke.

The INTERSTROKE study – although limited by its matched case-control design vs. a prospective cohort approach – nonetheless represents an efficient approach to obtaining useful information about stroke risk. The important findings of this study should help inform worldwide stroke prevention strategies and reduce the global burden of stroke.

JACK V. TU, M.D., is with the Institute for Clinical Evaluative Sciences, the Sunnybrook Health Sciences Centre, and the University of Toronto. His comments were originally published in the Lancet (2010 June 18 [

doi:10.1016/S0140-6736(10)60975-0

Ten Risk Factors Key to Global Stroke Risk