Title: Common Peripheral Inflammatory Diseases: An Underestimated Stroke Risk Factor
Funder: Stroke Association

Abstract: Many strokes can be explained by risk factors like high blood pressure or atrial fibrillation (irregular heartbeat). However, about 1 in 3 ischaemic strokes are cryptogenic – that is, they have no obvious cause. In people under 50, this number rises to 1 in 2. In this project, Dr Kieron South will be looking at a possible risk factor that might explain some of these cryptogenic strokes: long-term inflammation caused by inflammatory diseases like asthma and rheumatoid arthritis. What are the aims of this research? We already have some information on the likelihood of stroke among people with inflammatory diseases, but we do not know about how that likelihood changes over time as people experience flare-ups or go through immunosuppressive treatments. Kieron’s first task will be to look at how these can influence the risk of a stroke by examining health records in detail. Kieron will then move on to assessing blood samples from people with inflammatory diseases, comparing those who have gone on to have a stroke with those who haven’t. He’ll be looking for proteins in the blood that are linked to both blood clotting and inflammation to see if he can find more specific ways to predict who is at risk of a stroke. In the last stage, Kieron will be focusing on one of these proteins, called Von Willebrand Factor (VWF). VWF is involved in many inflammatory diseases and in blood clotting, but we don’t yet understand how it might affect stroke risk. The best way to find out is to examine what’s happening in living creatures, so Kieron will look at mice with inflammatory diseases to see whether levels of VWF factor are higher when they are having a disease flare, and test whether anti-inflammatory treatments or treatments targeting VWF can reduce the likelihood or severity of a stroke in these mice. What are the benefits of this research? Kieron’s work will give us a better understanding of the links between inflammation and stroke and give us an indication of what drugs might help to prevent strokes in people with inflammatory diseases. If all goes well, this will lead to better early detection of those who are at risk of stroke, as well as new stroke-prevention drugs becoming available in the clinic. Excitingly, this research may be particularly helpful in preventing strokes in younger adults. Many inflammatory diseases, including asthma and inflammatory bowel disease, are most likely to start in our teens and twenties. Kieron says, “By identifying potential causes of stroke in young adults I hope to contribute to its primary prevention. I hope that my work will add to our understanding of the underlying causes of stroke in young adults and may improve its clinical diagnosis, particularly in individuals who do not have a history or clinical signs of the most common cardiovascular risk factors.”

Lay abstract: Many strokes can be explained by risk factors like high blood pressure or atrial fibrillation (irregular heartbeat). However, about 1 in 3 ischaemic strokes are cryptogenic – that is, they have no obvious cause. In people under 50, this number rises to 1 in 2. In this project, Dr Kieron South will be looking at a possible risk factor that might explain some of these cryptogenic strokes: long-term inflammation caused by inflammatory diseases like asthma and rheumatoid arthritis. What are the aims of this research? We already have some information on the likelihood of stroke among people with inflammatory diseases, but we do not know about how that likelihood changes over time as people experience flare-ups or go through immunosuppressive treatments. Kieron’s first task will be to look at how these can influence the risk of a stroke by examining health records in detail. Kieron will then move on to assessing blood samples from people with inflammatory diseases, comparing those who have gone on to have a stroke with those who haven’t. He’ll be looking for proteins in the blood that are linked to both blood clotting and inflammation to see if he can find more specific ways to predict who is at risk of a stroke. In the last stage, Kieron will be focusing on one of these proteins, called Von Willebrand Factor (VWF). VWF is involved in many inflammatory diseases and in blood clotting, but we don’t yet understand how it might affect stroke risk. The best way to find out is to examine what’s happening in living creatures, so Kieron will look at mice with inflammatory diseases to see whether levels of VWF factor are higher when they are having a disease flare, and test whether anti-inflammatory treatments or treatments targeting VWF can reduce the likelihood or severity of a stroke in these mice. What are the benefits of this research? Kieron’s work will give us a better understanding of the links between inflammation and stroke and give us an indication of what drugs might help to prevent strokes in people with inflammatory diseases. If all goes well, this will lead to better early detection of those who are at risk of stroke, as well as new stroke-prevention drugs becoming available in the clinic. Excitingly, this research may be particularly helpful in preventing strokes in younger adults. Many inflammatory diseases, including asthma and inflammatory bowel disease, are most likely to start in our teens and twenties. Kieron says, “By identifying potential causes of stroke in young adults I hope to contribute to its primary prevention. I hope that my work will add to our understanding of the underlying causes of stroke in young adults and may improve its clinical diagnosis, particularly in individuals who do not have a history or clinical signs of the most common cardiovascular risk factors.”

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE