Abstract
Rist et al (1). performed a quantitative systematic review of studies investigating the association between migraine and cervical artery dissection (CAD). Five observational case-control studies were identified. In the pooled analysis, migraine doubled the risk of CAD, (OR 2.06, 95% CI 1.33 to 3.19). The risk did not seem to differ significantly by aura status or gender.
The systematic review and meta-analysis conducted by Rist et al. (1) adhered to the highest of methodological standards. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies were adopted (2). The clinical problem, hypothesis, and objectives were clearly outlined. A sensible well defined set of study eligibility criteria was assembled and applied. Convincing efforts were made to locate all relevant articles in major electronic bibliographic databases, without language restrictions. A description of methodological quality of each included article was presented. The literature search, screening, application of eligibility criteria, article selection, and data extraction were all completed by two independent investigators. Differences were resolved by consensus. Heterogeneity among the included studies was low to moderate, justifying pooling. The investigators provided the reasoning behind their choice of meta-analysis tool, a random effects model. Risk of publication bias was properly assessed. Summary estimates of association (odds ratio) and precision estimates (95% confidence interval) were provided. The results were valid and compelling. Sensitivity analyses proved the results to be robust.
The results will inspire continued vigorous investigation of the exact mechanisms behind the association between migraine and CAD, circumstances not unlike those of the association between patent foramen ovale (PFO) and migraine (3). Vanmolkot et al. proposed that migraineurs may have inherently altered arterial properties that may account for the increased risk of vascular disorders such as stroke, Raynaud’s phenomenon, angina, and cervical artery dissection (4). Significant findings among migraineurs included higher systolic blood pressure and mean arterial blood pressure, smaller diameter muscular arteries, increased vascular tone, and impaired endothelial function compared with age- and sex-matched controls. Vargas et al. have theorized the presence of an arteriopathy among some migraineurs (5). In support of endothelial dysfunction in patients with migraine, Lee et al. demonstrated lower levels of endothelial progenitor cells (EPCs) in migraineurs (6). Decreased numbers of EPCs have been independently associated with increased risk of cardiovascular events. Patients with migraine and CAD, like patients with migraine and PFO, may share common genetic composition and susceptibility factors (7). Increased activity of serum elastase in migraineurs provides one potential physiological explanation for an increased risk of CAD (8).
Finally, could cervical manipulative therapy (CMT) partly confound the association between migraine and CAD? One million patients per year visit a chiropractor for CMT, many of whom seek assistance for migraine. Weak to moderate strength of evidence for causation exists between CMT and CAD and associated stroke, especially in young adults (9). For example, young patients who sustained a vertebrobasilar artery territory stroke were five times more likely than controls to have had CMT within 1 week of the stroke event date (OR 5.03, 95% CI, 1.32 to 43.87) (10). The best available estimate of incidence of CAD is approximately 1.3 cases attributable to CMT for every 100,000 people<45 years of age receiving CMT (10).
Strong links have already been discovered to exist between migraine and the vascular system. Now, the confirmed association between migraine and CAD should fuel further scientific inquiries into the most probable and compelling mechanisms.