Leukocyte count as an independent predictor of recurrent ischemic events.
OBJECTIVE
Inflammatory markers predict first-time ischemic events. We investigated whether leukocyte and differential counts predict recurrent events and ischemic events in high-risk populations, and whether such events are preceded by acutely exacerbated inflammation.


METHODS
We studied 18 558 patients with ischemic stroke, myocardial infarction, or peripheral arterial disease who participated in the trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE), a study that compared the occurrence of ischemic stroke, myocardial infarction, or vascular death under randomized treatment with aspirin or clopidogrel. Leukocyte counts were frequently assessed during followup.


RESULTS
Compared with the quartile with lowest leukocyte counts at baseline (<5.9x10(9)/L), patients in the top quartile (>8.2x10(9)/L) had higher risks for ischemic stroke (relative risk 1.30; P=0.007), myocardial infarction (relative risk 1.56, P<0.001), and vascular death (relative risk 1.51; P<0.001) after adjustment for other risk factors. Neutrophil counts contributed most to increased risk. Assessments of regression dilution effects based on replicate measurements show that these risk associations may underestimate the real associations by 30 to 50%. Treatment with aspirin or clopidogrel did not influence predictive effects by leukocytes. In the week before a recurrent event, but not at earlier time points, the leukocyte count was significantly increased over baseline levels (n=211; mean difference +0.46x10(9)/L; P=0.005).


CONCLUSIONS
Leukocyte counts and mainly neutrophil counts are independently associated with ischemic events in these high-risk populations. An increase of leukocyte counts over baseline levels heralds a period of increased risk lasting about one week.
Grau
Armin J
AJ
Neurologische Klinik, Klinikum der Stadt Ludwigshafen a.Rh., Bremserstr. 70, D-67063 Ludwigshafen, Germany. graua@klilu.de
Boddy
Alexander W
AW
Dukovic
Deborah A
DA
Buggle
Florian
F
Lichy
Christoph
C
Brandt
Tobias
T
Hacke
Werner
W
D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis; D002423:Cause of Death; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D007958:Leukocyte Count / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000188:drug therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015415:Biomarkers; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin