Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

Cervical artery dissection goes frequently undiagnosed.

Cervical artery dissection (CeAD) is a frequent cause of stroke among young patients. It is unclear how many CeADs occur asymptomatically or cause subtle and unspecific clinical symptoms. We hypothesize that CeAD remains often unrecognized. Accordingly, the incidence of CeAD might be higher and the stroke risk lower than generally assumed. Lack of CeAD-indicating clinical symptoms is regarded as the main cause of missed diagnoses. We further hypothesize that underrepresentation of asymptomatic and oligosymptomatic patients in CeAD studies may have biased the association between ischemia and local symptoms in CeAD patients as well as the associations of CeAD with risk factors or co-morbidities. We finally hypothesize that symptomatic CeAD may be preceded by an initial asymptomatic phase. According to this final hypothesis, the time of onset of CeAD should be considered uncertain. The issue of unrecognized CeAD is relevant, as it may affect the associations between CeAD and putative risk factors. Furthermore, the existence of clinically silent CeADs may explain why recurrent and familial CeAD have been rarely observed

Age-dependent differences in cervical artery dissection.

13nonenoneMetso TM; Debette S; Grond-Ginsbach C; Engelter ST; Leys D; Brandt T; Pezzini A; Bersano A; Kloss M; Thijs V; Lyrer PA; Tatlisumak T; Metso AJ.Metso, Tm; Debette, S; Grond Ginsbach, C; Engelter, St; Leys, D; Brandt, T; Pezzini, Alessandro; Bersano, A; Kloss, M; Thijs, V; Lyrer, Pa; Tatlisumak, T; Metso, A. J

Towards understanding seasonal variability in cervical artery dissection (CeAD).

Cervical artery dissection (CeAD) occurs more often in autumn or winter than in spring or summer. We searched for clinical variables associated with this seasonality by comparing CeAD patients with onset of symptoms in autumn–winter (September 22–March 21) versus those with first CeAD symptom in spring–summer (March 22–September 21). We performed a cross-sectional study using data from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) registry. Age- and sex-matched patients with ischemic stroke attributable to a cause other than CeAD (non-CeAD patients) were analyzed to study the specificity of our findings. Autumn–winter CeAD patients had a higher median brachial pulse pressure at admission (55 vs. 52 mmHg; p = 0.01) and more recent infections (22.0% vs. 16.6%; p = 0.047), but prevalence of trauma was not associated with seasonal onset. Multivariable logistic regression analysis revealed that higher pulse pressure was significantly associated with autumn–winter CeAD (p = 0.01), while age, gender, history of hypertension, recent infection, and recent trauma were not. No association between pulse pressure and seasonal occurrence was found in non-CeAD ischemic stroke patients. Increased pulse pressure was associated with the higher frequency of CeAD in autumn or winter

Gender and cervical artery dissection.

Background and purpose: To analyze previously established gender differences in cervical artery dissection (CeAD). Methods: This case-control study is based on the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) population comprising 983 consecutive CeAD patients (mean age: 44.1±9.9years) and 658 control patients with a non-CeAD ischemic stroke (IS) (44.5±10.5years). Results: Cervical artery dissection was more common in men (56.7% vs. 43.3%, P<0.001) and men were older (46.4 vs. 41.0years, P<0.001). We assessed putative risk factors for CeAD including vascular risk factors, recent cervical trauma, pregnancies, and infections. All gender differences in the putative risk factors and outcome were similar in the CeAD and the non-CeAD IS groups. Conclusion: Our analysis of the largest collection of CeAD patients to date confirms male predominance and differences in age at dissection between men and women. Gender differences in putative risk factors may explain the higher frequency of CeAD in men and their older age, but the putative risk factors are probably not specific for CeAD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe