The objective is to investigate mechanisms of recurrent stroke. This study is based on plasma samples taken on enrolment from a subset of the 6105 subjects in the perindopril protection against recurrent stroke (PROGRESS) study. The PROGRESS study was a randomized double-blind controlled study of a perindopril-based blood pressure lowering regimen among individuals with stroke or transient ischemic attack within the previous 5 years. This project has two main aims: 1. To identify whether NMR-determined lipoprotein profiles, and plasma levels of homocysteine, protein carbonyls, chlorotyrosine, soluble vascular cell adhesion molecule (sVCAM-1), C-reactive peptide (CRP), active renin, and the amino-terminal pro-B-type natriuretic peptide (NT-proBNP) predict recurrent stroke in PROGRESS study participants. 2. To identify whether nuclear magnetic resonance (NMR)-determined lipoprotein profiles, and plasma levels of homocysteine, protein carbonyls, chlorotyrosine, sVCAM-1, CRP, active renin, and NT-proBNP predict benefit from perindopril-based antihypertensive therapy. This will be a nested case-control study. From the plasma samples obtained from 6105 subjects on enrolment in the PROGRESS study, 727 are from subjects who experienced recurrent stroke during the study. Our cases will be the 325 from this 727 from whom plasma samples were collected more than one month after the qualifying event and frozen at -80xC within 24 hours. Each case will be matched to two control subjects who had no cardiovascular event. The data will be related to clinical markers of cardiovascular risk on enrolment. We will determine which of these plasma markers provides an independent measure of risk of recurrent stroke. In addition, we will determine those plasma markers that provide an independent measure of reduction in risk of recurrent stroke by perindopril-based antihypertensive therapy, thereby providing a means to identify those subjects most likely to benefit from such therapy, and conversely, those subjects in whom alternative preventative strategies are required. In addition, plasma markers that predict risk of recurrent stroke may indicate novel therapies to prevent this condition.
