Plasma and genetic inflammatory markers as prognostic indicators innon-disabling cerebrovascular disease

TIA and minor stroke confer increased risk of further vascular events, with resulting morbidity and mortality. Inflammation is implicated in the pathogenesis and outcome of vascular disease and cerebral ischaemia. Circulating inflammatory markers or inflammatory gene polymorphisms may indicate those at greatest risk of major vascular events. The primary hypothesis of this work is that plasma concentrations of interleukin-1 receptor antagonist (IL-1 RA), IL-6 and C-reactive protein (CRP), and/or inflammatory genotypes, measured after a recent TIA or minor stroke predict the short-term risk of recurrent vascular events (the primary outcome). In a prospective study of 711 patients recruited at a median of 15 days after TIA or minor stroke, baseline plasma IL-1RA, IL-6 and CRP concentrations were not associated with the primary outcome. However, in a secondary analysis, ESR was significantly associated with outcome (OR 1.39, 95% CI=1.03-1.85, p=O.03). An exploratory analysis of single nucleotide polymorphisms (SNP) in six inflammatory genes indicated that IL-1A, IL-6 and {3-fibrinogen genotypes were significantly associated with primary outcome. This large cohort is representative of the patient population attending a range of regional UK secondary prevention services. Most markers of the acute inflammatory response are not of prognostic value in this group. Several reasons for this, including late clinical presentation, are discussed. However, delayed or chronic inflammation and its genetic determinants may yet have prognostic importance and are worthy of further study.EThOS - Electronic Theses Online ServiceGBUnited Kingdo