Risk factors for cervical artery dissection: a systematic review with meta-analysis

Cervical artery dissection (CAD) is a rare cause of stroke. This is an update of an earlier systematic review, which focuses on the risk of CAD in the general population. The objective was to identify the risk factors for CAD. A comprehensive search was conducted in MEDLINE, EMBASE and Web of Science on 20 September 2024. Observational studies (cohort, case-control studies and case-crossover studies) that studied patients with CAD and a control group were included. Risk of bias was assessed with the ROBINS-E tool, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). The results were stratified by healthy controls (primary analyses) and other control groups, notably ischaemic non-CAD stroke (secondary analyses). In total, 128 study reports were identified, of which 54 used one or more healthy control groups. Of these reports, 49 (91%) used a case-control design. The risk of bias was generally high (93%). For the following categories, effects were identified: (1) genetic factors or factors with a familial predisposition: migraine, methylenetetrahydrofolate reductase (MTHFR), TT homozygosity, matrix metalloproteinases (MMP) concentration, and connective tissue disorders; (2) external factors: recent infection, winter or autumn-winter season and oral contraceptive use; (3) minor trauma; (4) cardiovascular factors: hypertension, hypercholesterolaemia, relative vasodilatation of internal carotid, coronary artery disease and other cardiac diseases. For other risk factors (5), there were no significant pooled estimates. The certainty of the evidence was moderate for migraine and MTHFR TT, low for minor trauma and very low certainty for all others. This is the first review that comprehensively examined the risk of CAD in the general population. Genetic factors, cardiovascular risk factors, recent infection and minor trauma are risk factors for CAD. Caution is needed in interpretation as the evidence is overall low to very low certainty, except for migraine and MTHFR TT homozygosity.