Associations of inflammatory and hemostatic variables with the risk of recurrent stroke.
OBJECTIVE
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 (n=472) and hemorrhagic (n=83) 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.


CONCLUSIONS
Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.
Woodward
Mark
M
George Institute for International Health, University of Sydney, Australia.
Lowe
Gordon D O
GD
Campbell
Duncan J
DJ
Colman
Sam
S
Rumley
Ann
A
Chalmers
John
J
Neal
Bruce C
BC
Patel
Anushka
A
Jenkins
Alicia J
AJ
Kemp
Bruce E
BE
MacMahon
Stephen W
SW
D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis*; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000737:chemistry; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D005340:Fibrinogen / Q000096:biosynthesis / Q000737:chemistry; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis*; D020300:Intracranial Hemorrhages / Q000175:diagnosis*; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020913:Perindopril / Q000627:therapeutic use; D010919:Placebos; D012008:Recurrence; D012306:Risk; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000473:pathology*
D005338:Fibrin Fibrinogen Degradation Products; D010919:Placebos; C036309:fibrin fragment D; D005340:Fibrinogen; D002097:C-Reactive Protein; D020913:Perindopril