There was an urgent need to design more effective stroke prevention strategies. Previous prevention strategies including blood pressure control and anti-platelet therapy resulted in only a 43% reduction in stroke risk in a multi-center study, PROGRESS. Other proposed potentially modifiable mechanisms that mediated endothelial cell injury and activation leading to accelerated atherosclerosis including dyslipidemia, oxidative stress, endothelial dysfunction, inflammation, and renin-angiotensin system (RAS) activation were candidate strategies. Plasma markers of these various proposed mechanisms were studied to see if they predicted recurrent stroke. Since strokes kill 5 million people each year, at least one third of the 15 million others who sustain a non-fatal stroke suffer permanent disability, and those who have a transient ischemic attack (TIA) are also likely to have a recurrent event, identifying potentially modifiable risk factors would significantly reduce morbidity and mortality due to strokes worldwide.