Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment.
OBJECTIVE
The factor V Leiden mutation is associated with ischemic stroke in children but not in adults. Whether it is associated with ischemic stroke in young adults, however, is uncertain.


METHODS
To address this issue, we performed a meta-analysis of 18 case-control studies of ischemic stroke in adults 50 years of age and younger published before June 2009.


RESULTS
Across all studies, factor V Leiden was detected in 154 of 2045 cases (7.5%) and 217 of 5307 controls (4.1%), yielding a fixed-effect odds ratio of 2.00 (95% CI, 1.59-2.51). However, further analyses revealed substantial heterogeneity among these studies (P=0.005 for Q-test of heterogeneity). Hypothesizing that this heterogeneity could be related to differences among studies in case selection criteria, we stratified the meta-analysis into studies for which case samples were enriched or not enriched to include cases having an increased likelihood of prothrombotic genetic involvement ("selected" ischemic stroke studies, n=9) and those that recruited cases from consecutive neurology referrals or hospitalizations ("unselected" ischemic stroke studies, n=8). Among the 9 "selected" ischemic stroke studies, factor V Leiden was more strongly associated with stroke (OR, 2.73; 95% CI, 1.98-3.75), whereas among the 8 "unselected" ischemic stroke studies, the association between factor V Leiden and stroke was substantially weaker (OR, 1.40; 95% CI, 0.998-1.95). This difference was found to be statistically significant (P=0.003 for Woolf test for heterogeneity).


CONCLUSIONS
We conclude that factor V Leiden is associated with ischemic stroke in young adults, particularly in patient populations in which there is an increased clinical suspicion of prothrombotic state.
Hamedani
Ali G
AG
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201-1509, USA.
Cole
John W
JW
Mitchell
Braxton D
BD
Kittner
Steven J
SJ
D002545:Brain Ischemia / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D055815:Young Adult
C095381:factor V Leiden; D005165:Factor V