Protein Z in ischemic stroke and its etiologic subtypes.
OBJECTIVE
Protein Z is a vitamin K-dependent plasma protein whose significance in arterial thrombosis remains uncertain. The objectives of this study were to determine the association between protein Z, ischemic stroke, and etiologic subtypes of ischemic stroke.


METHODS
We conducted a case-control study of 173 hospital cases of first-ever ischemic stroke and 186 randomly selected community controls. Using established criteria, we classified cases of stroke by etiologic subtype. Protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event.


RESULTS
Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 microg/mL; P<0.0001). Compared with the lowest tertile, the upper 2 tertiles of protein Z were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.75 (95% CI, 1.00 to 3.07) for the second tertile and 3.07 (95% CI, 1.73 to 5.45) for the upper tertile. The adjusted odds of ischemic stroke caused by large-artery atherothrombosis was nearly 8-fold greater for those with protein Z concentrations in the upper tertile compared with the lower tertile (OR, 7.91; 95% CI, 3.11 to 20.14). The adjusted odds of ischemic stroke due to small-artery disease (OR, 1.79; 95% CI, 0.83 to 3.87) and cardioembolism (OR, 1.80; 95% CI, 0.58 to 5.64) was also increased among individuals with protein Z concentrations in the upper tertile compared with the lower tertile, but not significantly so. There was no significant difference between mean protein Z concentrations among cases in the convalescent phase (3 months) after stroke and age- and sex-matched controls.


CONCLUSIONS
There is a strong, independent relationship between elevated blood levels of protein Z and ischemic stroke during the acute phase, particularly ischemic stroke due to large-artery atherothromboembolism, which is no longer evident during the convalescent phase. These results are consistent with the notion that protein Z is either an important factor in the pathogenesis of ischemic stroke due to large-artery atherothromboembolism or an acute phase reactant. Further studies are required to elucidate whether protein Z has a causative or prognostic role in acute arterial thrombosis.
McQuillan
Andrew M
AM
Department of Hematology, Royal Perth Hospital, Box X2213 GPO, Perth, WA 6897, Australia.
Eikelboom
John W
JW
Hankey
Graeme J
GJ
Baker
Ross
R
Thom
Jim
J
Staton
Janelle
J
Yi
Qilong
Q
Cole
Vanessa
V
D017677:Age Distribution; D000368:Aged; D001798:Blood Proteins / Q000032:analysis*; D002545:Brain Ischemia / Q000097:blood* / Q000145:classification / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012307:Risk Factors; D017678:Sex Distribution; D020521:Stroke / Q000097:blood* / Q000145:classification / Q000453:epidemiology; D014904:Western Australia / Q000453:epidemiology
D001798:Blood Proteins; C026080:plasma protein Z