ISC 2009: Low-Income Countries Bear Biggest Burden of Stroke

Susan Jeffrey

February 24, 2009

February 24, 2009 (San Diego, California) — A new analysis of global surveillance data shows rates of stroke mortality and burden vary between countries, but lower-income countries appear to be most affected.

After age adjustment, there was a 10-fold difference in rates of stroke mortality and disability-adjusted life-years (DALYs) between the most and least affected countries, with national per-capita income being the strongest predictor of mortality and DALY loss, even after adjustment for cardiovascular risk factors.

Dr. S. Claiborne Johnston

"Stroke is a big problem in low- and middle-income countries, and it requires specific attention," lead author S. Claiborne Johnston, MD, from the University of California, San Francisco, told Medscape Neurology & Neurosurgery. "We need to develop a research agenda that recognizes the importance of stroke in those countries and the unique approaches that are going to be required to get it under control."

The results were presented at the American Stroke Association International Stroke Conference 2009 and published online February 20 in Lancet Neurology.

Global Burden

The researchers undertook the study, Dr. Johnston said, "because almost all of the research that's been done about stroke and our understanding of the risk factors, burdens, and interventions has all been based on what happens in high-income countries. But most of the strokes, we know, are not occurring in those countries."

However, funding for surveillance is not available in low- and middle-income countries, and global health foundations have been largely focused on infectious diseases in these areas. "Our goal was just to see what's going on in the rest of the world and try to understand what produces differences in stroke risk on a national level," he said.

Funded by the World Health Organization, they aimed to develop national estimates of stroke mortality and burden, expressed in DALYs, calculated from monitoring vital statistics, a systemic review of studies that reported disease surveillance, and modeling as part of the WHO Global Burden of Disease program.

They used the same methods to generate standardized measures of the national prevalence of cardiovascular risk factors. Risk factors other than diabetes and disease-burden estimates were age- and sex-adjusted to the WHO standard population, the authors note.

They found a 10-fold difference in the rates of stroke mortality and DALY loss between the most affected and least affected countries. Rates were highest in Eastern Europe, North Asia, Central Africa, and the South Pacific.

Sampling of 192 Countries Ranked by Age-Adjusted Stroke Mortality (From Highest to Lowest, Median 111 per 100,000)

Ranking Country Mortality (per 100,000)
1 Russia 251
2 Kyrgyzstan 237
3 St. Kitts and Nevis 216
20 Democratic Republic of Congo 162
184 Australia 33
186 United States 32
189 Canada 27
191 Switzerland 26
192 Seychelles 24

National per-capita income was the strongest predictor of mortality and DALY loss (P < .001), even after adjustment for cardiovascular risk factors (P < .001), they write. "Prevalences of cardiovascular risk factors measured at a national level were generally poor predictors of national stroke mortality rates and burden, although raised mean systolic blood pressure (P = .028) and low body-mass index (P = .017) predicted stroke mortality, and greater prevalence of smoking predicted both stroke mortality (P = .041) and DALY-loss rates (P = .034).

Dr. Johnston speculated that the lack of association between stroke mortality and risk factors may relate to measurement issues. "It suggests that the surveillance that we do in these countries is inadequate to address the underlying risk factors," he said. In addition, the data may be confounded by the income issue. Case fatality is higher where there is little stroke care, and risk factors such as hypertension, for example, will be higher when only a small segment of the population is able to obtain antihypertensive medications.

The data suggest more needs to be done to address the risk for stroke in lower-income areas of the world, with an emphasis on cost-effectiveness, he said. Provision of tissue plasminogen activator (tPA), for example, "is not the answer in low- and middle-income countries. We need to think about prevention and more cost-effectiveness for prevention."

They hope to push forward secondary stroke prevention in particular, he added. "The interventions tend to be more cost-effective than in primary prevention, but secondary-prevention practices are almost nonexistent in many low-income countries."

One potential strategy is development of a "polypill" that would include, for example, antihypertensive medications and a statin, although the drugs that would make up the polypill are still a matter of debate. "Developing a specific stroke polypill is on the radar, and hopefully that will move forward as the WHO's other polypill research moves forward," he concluded.

The "Time for Action"

In a separate systematic review article published at the same time in Lancet Neurology, researchers with first author Valery L. Feigin, MD, from AUT University, in Auckland, New Zealand, look at stroke incidence and early case fatality rates reported in 56 population-based studies.

They found a divergent and statistically significant trend in stroke incidence rates over the past 4 decades, with a 42% decrease in stroke incidence in high-income countries and a greater-than-100% increase in low- to middle-income countries. Further, between 2000 and 2008, overall stroke incidence rates in low- and middle-income countries exceeded those of higher-income countries by 20% for the first time.

"The time to decide whether or not stroke is an issue that should be on the governmental agenda in low- to middle-income countries has now passed," Dr. Feigin and colleagues conclude. "The time for action is now."

Important Observations

In a Reflection and Reaction article accompanying the papers, Martin O'Donnell, MD, and Salim Yusuf, MD, from McMaster University and Hamilton General Hospital, in Hamilton, Ontario, point out that these 2 reports "present important and related epidemiological observations on global stroke incidence."

While both are "exhaustive and complete," they note, the reports highlight current deficits in the study of determinants of stroke risk in low- and middle-income countries, where most strokesoccur.

In coronary heart disease, large studies like INTERHEART as well as the GRACE and CREATE registries, they write, "have enabled us to tailor population-based prevention and treatment strategies to such regional variation."

One such study, on which the editorialists are both principal investigators, is INTERSTROKE, a new standardized, case-control study looking at the importance of established and emerging risk factors for the common stroke subtypes in different regions and ethnic groups in low-, middle- and high-income studies. The study will use the same methods as the INTERHEART study, they note, "which found that 9 easily measured risk factors accounted for more than 90% of the population-attributable risk for myocardial infarction, globally and in each region.

"Population-based stroke-prevention programs and the epidemiological studies that are used to inform and monitor them are urgently required in low-income countries," Drs. O'Donnell and Yusuf conclude. "On the basis of successful experiences in cardiovascular disease, such studies should now be feasible in stroke."

Dr. Johnston's study was funded by the World Health Organization. The authors report no conflict of interest. Dr. Feigin and colleagues report no conflict of interest. Drs. O'Donnell and Yusuf report they are principal investigators of the INTERSTROKE Study.

American Stroke Association International Stroke Conference 2009, San Diego, California: Abstract 154. Presented February 20, 2009.

Lancet Neurol. 2009. Published online February 20, 2009. Abstract Abstract Abstract

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