Associations of Inflammatory and Hemostatic Variables With the Risk of Recurrent Stroke

Abstract

Background and Purpose-Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin D-dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Methods-Nested case-control study of ischemic (nϭ472) and hemorrhagic (nϭ83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. Results-Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and D-dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance. here is increasing evidence that hemostatic and inflammatory variables are associated with cardiovascular events in prospective studies, including coronary heart disease (CHD) and stroke. 1 Most data are available for fibrinogen, which may play a causal role in atherothrombotic events through effects on atherogenesis, thrombogenesis, or ischemia distal to atherothrombotic stenoses or occlusions. [1][2][3][4] Several prospective studies have reported that fibrinogen is associated with risk of stroke, 5-9 although not the Caerphilly and Speedwell studies. 10 Plasma fibrinogen is an important determinant of plasma and blood viscosity, which have also been reported to be associated with the risk of CHD, 11-15 although reports for stroke have been conflicting. 10,13 In part, the possible association between viscosity and stroke may be mediated by an association between viscosity and elevated carotid intima-media thickness, at least in men. 16 Ernst et al 17 observed that fibrinogen, plasma viscosity, blood viscosity, and cholesterol were associated with risk of recurrence over 2 years in 523 survivors of first stroke. Similar findings have been reported for recurrent myocardial infarction. 18 There are fewer published data on the association of other hemostatic or inflammatory variables with risk of CHD and stroke. 1 Recent meta-analyses have shown that C-reactiv...

The Role of D-Dimer, Fibrinogen and C-Reactive Protein as Plasma Biomarkers in Acute Ischemic Stroke

“…Fibrinogen is a thrombotic risk factor which also acts as an acute phase protein. Elevated levels of fibrinogen have been reported after stroke [4] and have been associated with increased risk of recurrent stroke [9].…”

C–reactive Protein and Early Mortality in Acute Ischemic Stroke

“…[6][7][8][9] In metaanalysis of studies of long term follow up, Preindropil Protection Against Recurrent Stroke (PROGRESS) clinical trial and "Benzfibrate Infarction Prevention (BIP) Study" the figures for recurrent event was 1.7, 1.34 and more than two fold increased risk in highest versus lowest tertile group respectively. [10][11][12] In addition, raised CRP levels may reflect the clinical course of the condition extent of brain infarction and an adverse prognosis. [13][14][15][16] In all these studies focus was on mortality at one month and thereafter.…”

Hemorajik Ve İskemik İnme Ayırıcı Tanısında D-Dimer Ve Diğer Koagülasyon Belirteçlerinin Değerliliği

“…Woodward et al (27) , in their study covering 591 stroke patients (83 hemorrhagic, 472 ischemic), has shown that fibrinogen level was significantly higher in patients with ischemic stroke. In our study, fibrinogen levels of 65 of 100 patients were high (>3.5 g/L) and of these patients 24.6% had TIA, 43.1% had ischemic stroke, and 32.3% had hemorrhagic stroke.…”