It is worth noting though that all four studies found no association with cardioembolic stroke, consistent with our results. There is a potential explanation, speculative at this stage, which might explain the stronger association between air pollution and mild stroke, and which does not require considering the small vessel disease hypothesis. It may be that thrombus formation triggered by air pollutants is smaller, less dense or more easily broken down. In addition, atheromatous plaques induced by air pollutants may be more modest in size. With this hypothesis, the air pollution effect would not Inhibitors,Modulators,Libraries need to be preferentially associated with small vessel disease stroke as ischemic stroke caused by air pollutants could affect large and small arteries alike but the resulting clinical picture would tend to be that of a mild stroke.

We previously observed that air pollution exposure was more strongly associated with stroke mortality than with stroke hospital admissions. Others have also reported a stronger association with fatal than with non fatal stroke. This suggests that air pollution ought to be more strongly associated with severe stroke and is therefore not consistent Inhibitors,Modulators,Libraries with the results we have observed. However, a possible alternative explanation is that whilst air pollution is more strongly associated with mild stroke, exposure to high pollution reduces survival after stroke and it is the latter which accounts for the stronger association seen with stroke mortality. In this regard, we have previously reported a strong independent adverse effect of outdoor air pollution exposure on survival after stroke.

Internationally significant novelty The internationally significant novelty of our study results from two aspects. Firstly, air pollution is a widespread environmental hazard, with increasing levels of road traffic related air pollution encountered in many high and middle income countries across the globe. Secondly, Inhibitors,Modulators,Libraries ours is the first study to examine the chronic effects of outdoor Inhibitors,Modulators,Libraries air pollution on the incidence Inhibitors,Modulators,Libraries of ischemic stroke subtypes. Limitations There are a number of potential limitations to our study. The ecological study design is susceptible to ecological bias, which is the situation where the association seen at the area level is different from that which exists at the individual level. Ecological bias cannot be ruled out in our study.

However, we used a small area level ecological study design which would have mitigated ecological bias as small areas tend to be relatively more homogenous in terms of population characteristics and exposure to environmental pollutants. In addition, we compared effects on different stroke subtypes and severity within the same ecological study and any bias inherent in the study Sunitinib design might be expected to have similar effects on the different severity and subtype groups examined.