Air Pollution as an Emerging Global Risk Factor for Stroke

Ambient air pollution exposure is considered an important factor associated with mortality worldwide. In high-income countries, air pollution was associated with 2.5% of all deaths (eighth leading risk factor for mortality).¹ Increasing evidence suggests that the highest proportion of air pollution–related deaths, especially those related to particulate matter (PM), are not pulmonary related as might be speculated, but are due to cardiovascular causes. The American Heart Association concluded in an updated scientific statement that the overall evidence is consistent with PM playing a causal role in cardiovascular morbidity and mortality.² Although adverse cardiopulmonary outcomes have been the focus of most recent studies, air pollution–related stroke has received less attention. This relationship may represent a serious and increasing burden to populations, particularly in the developing world, and merits further attention on global research and public policy agendas.

Air pollution consists of a heterogeneous mixture of PM and gases (eg, ozone, carbon monoxide). Fossil fuel combustion (eg, traffic, power generation, industry) is a major source; however, indoor pollutants and the burning of biomass fuels are also significant contributors in many countries.² Early studies, including analyses of the Great London Fog of 1952, a renowned pollution episode of the 20th century, found an increased risk of stroke deaths attributable to a short-term extreme rise in air pollution.³ This relationship continues to be demonstrated even at lower levels. In most cases, exposure to each pollutant reported, including gases and particles of varying sizes, is associated with an increased risk of cerebrovascular events. Numerous between-study differences exist, including demographic characteristics, measured pollutants, temporal risk associations, and the ascertainment of stroke and stroke outcomes, making direct comparisons difficult. However, the relative risk for stroke-related mortality may reach 2.04 for a 21.3 μg/m³-increase in same-day PM₁₀ levels (elderly individuals in Seoul, South Korea),⁴ whereas the incidence rate increase for stroke hospitalizations may reach 13% (95% confidence interval [CI], 4%-22%) when previous-day PM₁₀ levels are greater than 30 μg/m³ vs less than 15 μg/m³ (in Sweden).⁵ In general, the risk of stroke appears to be greater for ischemic stroke compared with hemorrhagic stroke, and the association with PM is at least as strong as with gaseous pollutants.

In a prospective study that evaluated both stroke and heart disease outcomes in women,⁶ long-term exposure to air pollution was associated with an increased risk for a cerbrovascular disease event (odds ratio, 1.35; 95% CI, 1.08-1.68) that was comparable with that for myocardial infarction (odds ratio, 1.06; 95% CI, 0.85-1.34) and all coronary disease events (odds ratio, 1.21; 95% CI, 1.08-1.68).

However, some studies did not report a significant association between air pollution exposure and stroke risk. These studies suggested that the pollutant composition may be less harmful in some regions, some populations may be less susceptible, or that methodological differences (pollutant levels, study designs or power) could affect the reported stroke-exposure association. A variety of noncausal factors may also explain the different effects of air pollution on stroke compared with heart disease incidence. Stroke is more heterogeneous in nature (ischemic, hemorrhagic) and etiology (embolic, thrombotic), has no simple diagnostic biomarker, and involves costly confirmatory imaging. These factors may limit risk measurements for individual air pollutants and stroke using large national registries and community studies. Studies frequently consider hemorrhagic stroke and ischemic stroke as a single outcome although the risk profile and outcomes of hemorrhagic and ischemic stroke are distinct.

Studies from countries with higher air pollutant levels (Taiwan, China, South Korea) and comparatively lower air pollutant levels (Finland, Canada) demonstrate that short-term exposures are associated with a higher risk of stroke. For example, in the US Medicare population, elderly patients experienced an increase in stroke hospitalization on the same day of exposure to higher PM levels.⁷ In contrast, fewer prospective studies have reported stroke risk associated with longer-term PM exposures. One study showed fatal and total stroke risks associated with PM exposures were higher over the several years of follow-up than typically reported by shorter-term analyses.⁶ This suggests that for any given increase in air pollution level, there may be cumulative health effects of repeated or chronic exposures leading to comparatively higher stroke risks over several years of living in regions with more air pollution compared with the acute risk following relatively brief exposures.

Although the public health burden of air pollution–related stroke is significant in high-income countries (in which pollution levels have declined over past decades), the health effects associated with air pollution may be most important in developing countries, where approximately 85% of the world's population lives. Thirteen of the world's megacities (≥10 million inhabitants) are located in tropical regions. Biomass burning (affecting 3 billion individuals worldwide) has been estimated as the sixth leading contributing factor for death in developing countries.¹ Stroke is a major cause of mortality in these regions and accounts for 10% of all deaths globally—more than human immunodeficiency virus/AIDS and tuberculosis combined.⁸ Hospital-based studies on stroke are inadequate in most developing regions: the health care–seeking behavior for stroke in the world's most polluted and populated regions is essentially unknown.

Rapid economic development in the world's largest populations will result in major changes to air quality as economic gains lead to increased energy demands, urbanization, transportation, and widespread industrialization. In southern African countries, 10% or less of rural dwellers have electricity with the exception of South Africa (27%).⁹ In Beijing, China, alone, 1466 cars are added to the roads each day.¹⁰ In some of the world's most polluted regions, including developing countries such as India, China, and Thailand, stroke risk factors may have more pronounced effects because they can be unrecognized, untreated, and disproportionately affect younger people.

The burgeoning risk of stroke in the world's largest economies has so far been attributed to the aging of society and accrual of risk factors typically associated with a westernized lifestyle. Air pollution studies are a reminder that environmental risk factors are also changing. Extrapolation of population data from high-income regions to developing regions misses unique ecological risk factors for stroke that predominantly occur in resource-poor populations. Although air pollution is just 1 of these risk factors, it is accompanied by other understudied risks for stroke in parts of the developing world, including heat waves, emerging tropical infections such as Trypansoma cruzi, widespread uptake in cigarette smoking, and high prevalence of low birth weight.

Thus, when an environmental risk factor has been studied and found to have modest importance in high-income settings, simple extrapolation of this knowledge to the developing world must be done with caution. The developing world holds unique and important lessons about environmental health that can ultimately be helpful to understanding and addressing the increasing global burden of chronic diseases, a burden that affects the majority of individuals everywhere.