These include disturbance of cortical excitability, cortical spreading depression, meningeal inflam- mation, and activation of the trigeminovascular system.603 However, factors contributing to the increased risk of stroke with migraine remain elusive. Clinical-epidemiological stud- ies have suggested several mechanisms. In 1 prospective study of patients <55 years of age, hypercoagulable states were more frequent in the migraine than the nonmigraine Multivariate analy- sis showed that migraine without aura was associated with a 2.88-fold increased risk for hypercoagulable diagnosis (95% CI, 1.14 7.28), but in the group with brain infarcts who were <50 years of age, only migraine with aura was independently associated with hypercoagulable states (OR, 6.81; 95% CI, The Stoke Prevention in Young Women Study (SPYW) reported a 50% increased risk of ischemic stroke in those with probable migraine and visual aura (OR, 1.5; Interrelationships among the ACE dele- tion/insertion (D/I) polymorphism (rs1799752), migraine, and CVD, including ischemic stroke, were investigated in the WHS cohort.606 The increased risk for CVD among migraineurs with aura was apparent only for carriers of the DD (RR, 2.10; 95% CI, 1.22 3.59; P=0.007) and DI (RR, 2.31; 95% CI, 1.52 3.51) genotypes, suggesting that the DD/ DI genotype may play a role in, or at least be a marker for, this However, because of the small num- bers, further studies are warranted. Perhaps the most heavily investigated potential mecha- nistic link between migraine and stroke is the association of migraine and PFO. 