Many risk factors associated with ischaemic stroke are known, including hig
h levels of fibrinogen or factor VII. Protein Z is a vitamin K-dependent co
agulation factor, which was found to promote the assembly of thrombin with
phospholipid vesicles that might promote coagulation. Indeed, a low protein
Z level may be associated with a varying bleeding tendency. Therefore, we
hypothesized that high protein Z levels could induce a hypercoagulable stat
e and performed a case-control study to investigate a potential association
between high protein Z plasma levels and ischaemic stroke. We measured pro
tein Z in plasma samples from 157 patients with stroke of unknown aetiology
and 192 control subjects. All patients had survived an ischaemic stroke or
transient ischaemic attack (TIA) for at least 2 months. We found an increa
sed relative risk of ischaemic stroke with increasing protein Z levels, wit
h an odds ratio of 4.3 [95% confidence interval (CI): 1.7-11] for protein Z
plasma levels greater than or equal to 160%. Excluding patients with a his
tory of venous thromboembolism from the analysis, the same result was obtai
ned (odds ratio 4.2; 95% CI: 1.6-11.2). Using a logistic regression model,
this association also remained significant (P = 0.04) after adjustment for
established risk factors. Our data indicated that a high plasma level of pr
otein Z is an independent risk factor for ischaemic stroke.