In the JournalsPerspective

INTERSTROKE: Modifiable risk factors may explain nine of 10 acute strokes

Ten modifiable risk factors, most importantly hypertension, account for approximately 90% of acute strokes worldwide, according to the INTERSTROKE case-control study published in The Lancet.

“This study is of an adequate size and scope to explore stroke risk factors in all major regions of the world, within key populations and within stroke subtypes,” Martin J. O’Donnell, MB, PhD, from Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, and HRB-Clinical Research Facility, NUI Galway, Ireland, said in a press release. “The wider reach confirms the 10 modifiable risk factors associated with 90% of stroke cases in all regions, young and older, and in men and women. The study confirms that hypertension is the most important modifiable risk factor in all regions, and the key target in reducing the burden of stroke globally.”

O’Donnell and colleagues conducted a case-control study in 32 countries across five continents of 13,477 patients with stroke (10,388 ischemic stroke, 3,059 intracerebral hemorrhage) matched by age and sex with 13,472 controls without stroke.

Risk factors

The researchers found the following factors to be independently associated with any stroke:

  • BP 140 mm Hg systolic or 90 mm Hg diastolic or history of hypertension: OR = 2.98; 99% CI, 2.72-3.28; population-attributable risk (PAR), 47.9%; 99% CI, 45.1-50.6;
  • ratio of apolipoprotein B to apolipoprotein A-I: OR for highest vs. lowest tertile = 1.84; 99% CI, 1.65-2.06; PAR for top two tertiles vs. lowest tertile, 26.8%; 99% CI, 22.2-31.9;
  • diet as assessed by modified Alternative Healthy Eating Index: OR for highest vs. lowest tertile = 0.6; 99% CI, 0.53-0.67; PAR for lowest two tertiles vs. highest tertile = 23.2%; 99% CI, 18.2-28.9;
  • waist-to-hip ratio: OR for highest vs. lowest tertile = 1.44; 99% CI, 1.27-1.64; PAR for top two tertiles vs. lowest tertile, 18.6%; 99% CI, 13.3-25.3;
  • psychosocial factors: OR = 2.2; 99% CI, 1.78-2.72; PAR, 17.4%; 99% CI, 13.1-22.6;
  • current smoking: OR = 1.67; 99% CI, 1.49-1.87; PAR, 12.4%; 99% CI, 10.2-14.9;
  • cardiac causes: OR = 3.17; 99% CI, 2.68-3.75; PAR, 9.1%; 99% CI, 8-10.2;
  • alcohol consumption: OR = 2.09 for heavy vs. never or former drinkers; 99% CI, 1.64-2.67; PAR for current vs. never or former drinkers, 5.8%; 99% CI, 3.4-9.7; and
  • diabetes: OR = 1.16; 99% CI, 1.05-1.3; PAR, 3.9%; 99% CI, 1.9-7.6.

According to the researchers, those 10 modifiable risk factors combined for 90.7% (ischemic stroke, 91.5%; intracerebral hemorrhage, 87.1%) of all PAR for all stroke worldwide.

O’Donnell and colleagues wrote that the PAR for the 10 risk factors was consistent across regions (range, 82.7% for Africa to 97.4% for Southeast Asia), sexes (men, 90.6%; women, 90.6%) and age groups (aged 55 years or younger, 92.2%; older than 55 years, 90%).

Hypertension was more associated with intracerebral hemorrhage than ischemic stroke, but the reverse was true for current smoking, diabetes, apolipoprotein ratio and cardiac causes (P < .0001 for all), according to the researchers.

Valery L. Feigin

Three main points

In a related editorial, Valery L. Feigin, MD, MSc, PhD, FAAN, and Rita Krishnamurthi, BSc, MApplSc, PhD, both from National Institute for Stroke and Applied Neurosciences, School of Public Health and Psychosocial Studies, Faculty of Health and Environmental Sciences, University of Technology in Northcote, Auckland, New Zealand, wrote that the study contains three key messages.

“First, stroke is a highly preventable disease globally, irrespective of age and sex,” they wrote. “Second, the relative importance of modifiable risk factors and their PAR necessitates the development of regional or ethnic-specific primary prevention programs. … Third, additional research on stroke risk factors is needed for countries and ethnic groups not included in INTERSTROKE, as well as definitive cost-effectiveness research on primary stroke prevention in key populations (eg, different age, sex, ethnicity or region).”

  by Erik Swain

Disclosure: The study was funded in part by AstraZeneca, Boehringer Ingelheim Canada, Merck and Pfizer Canada. O’Donnell, Feigin and Krishnamurthi report no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.

Ten modifiable risk factors, most importantly hypertension, account for approximately 90% of acute strokes worldwide, according to the INTERSTROKE case-control study published in The Lancet.

“This study is of an adequate size and scope to explore stroke risk factors in all major regions of the world, within key populations and within stroke subtypes,” Martin J. O’Donnell, MB, PhD, from Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, and HRB-Clinical Research Facility, NUI Galway, Ireland, said in a press release. “The wider reach confirms the 10 modifiable risk factors associated with 90% of stroke cases in all regions, young and older, and in men and women. The study confirms that hypertension is the most important modifiable risk factor in all regions, and the key target in reducing the burden of stroke globally.”

O’Donnell and colleagues conducted a case-control study in 32 countries across five continents of 13,477 patients with stroke (10,388 ischemic stroke, 3,059 intracerebral hemorrhage) matched by age and sex with 13,472 controls without stroke.

Risk factors

The researchers found the following factors to be independently associated with any stroke:

  • BP 140 mm Hg systolic or 90 mm Hg diastolic or history of hypertension: OR = 2.98; 99% CI, 2.72-3.28; population-attributable risk (PAR), 47.9%; 99% CI, 45.1-50.6;
  • ratio of apolipoprotein B to apolipoprotein A-I: OR for highest vs. lowest tertile = 1.84; 99% CI, 1.65-2.06; PAR for top two tertiles vs. lowest tertile, 26.8%; 99% CI, 22.2-31.9;
  • diet as assessed by modified Alternative Healthy Eating Index: OR for highest vs. lowest tertile = 0.6; 99% CI, 0.53-0.67; PAR for lowest two tertiles vs. highest tertile = 23.2%; 99% CI, 18.2-28.9;
  • waist-to-hip ratio: OR for highest vs. lowest tertile = 1.44; 99% CI, 1.27-1.64; PAR for top two tertiles vs. lowest tertile, 18.6%; 99% CI, 13.3-25.3;
  • psychosocial factors: OR = 2.2; 99% CI, 1.78-2.72; PAR, 17.4%; 99% CI, 13.1-22.6;
  • current smoking: OR = 1.67; 99% CI, 1.49-1.87; PAR, 12.4%; 99% CI, 10.2-14.9;
  • cardiac causes: OR = 3.17; 99% CI, 2.68-3.75; PAR, 9.1%; 99% CI, 8-10.2;
  • alcohol consumption: OR = 2.09 for heavy vs. never or former drinkers; 99% CI, 1.64-2.67; PAR for current vs. never or former drinkers, 5.8%; 99% CI, 3.4-9.7; and
  • diabetes: OR = 1.16; 99% CI, 1.05-1.3; PAR, 3.9%; 99% CI, 1.9-7.6.

According to the researchers, those 10 modifiable risk factors combined for 90.7% (ischemic stroke, 91.5%; intracerebral hemorrhage, 87.1%) of all PAR for all stroke worldwide.

O’Donnell and colleagues wrote that the PAR for the 10 risk factors was consistent across regions (range, 82.7% for Africa to 97.4% for Southeast Asia), sexes (men, 90.6%; women, 90.6%) and age groups (aged 55 years or younger, 92.2%; older than 55 years, 90%).

Hypertension was more associated with intracerebral hemorrhage than ischemic stroke, but the reverse was true for current smoking, diabetes, apolipoprotein ratio and cardiac causes (P < .0001 for all), according to the researchers.

Valery L. Feigin

Three main points

In a related editorial, Valery L. Feigin, MD, MSc, PhD, FAAN, and Rita Krishnamurthi, BSc, MApplSc, PhD, both from National Institute for Stroke and Applied Neurosciences, School of Public Health and Psychosocial Studies, Faculty of Health and Environmental Sciences, University of Technology in Northcote, Auckland, New Zealand, wrote that the study contains three key messages.

“First, stroke is a highly preventable disease globally, irrespective of age and sex,” they wrote. “Second, the relative importance of modifiable risk factors and their PAR necessitates the development of regional or ethnic-specific primary prevention programs. … Third, additional research on stroke risk factors is needed for countries and ethnic groups not included in INTERSTROKE, as well as definitive cost-effectiveness research on primary stroke prevention in key populations (eg, different age, sex, ethnicity or region).”

  by Erik Swain

Disclosure: The study was funded in part by AstraZeneca, Boehringer Ingelheim Canada, Merck and Pfizer Canada. O’Donnell, Feigin and Krishnamurthi report no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.

    Perspective
    Larry B. Goldstein

    Larry B. Goldstein

    The study reinforces the consistent message that stroke is commonly preventable. Much of the more than 30% decline in stroke-related mortality in the United States (and likely other industrialized countries) has been through improved prevention. These data should also lead to investments in stroke preventive measures in non-industrialized nations, where there is an increasing burden of non-communicable diseases.

    The study has limitations inherent in the design such as recall, measurement and ascertainment biases. In addition, although well-founded in prior research, the study identified associations, not causal relationships. Also, the study did not evaluate the impact of population-based intervention programs on outcomes.

    What is needed is the development of evaluable, culturally and regionally appropriate population-based risk intervention programs.

    • Larry B. Goldstein, MD, FAAN, FANA, FAHA
    • Cardiology Today Editorial Board Member Ruth L. Works Professor and Chairman, Department of Neurology Co-Director, Kentucky Neuroscience Institute KY Clinic – University of Kentucky, Lexington

    Disclosures: Goldstein reports no relevant financial disclosures.