Migraine a marker of vascular health?

Strong interrelationships between migraine and the vascular system have been known for decades (1). While there is an ongoing discussion on the primary role of the vascular system in triggering migraine attacks (2,3), there is increasing evidence that migraine, particularly migraine with aura, is a risk factor for stroke and potentially for other cardiovascular disease events (4). The reasons for this increased risk remain unclear, however. One potential explanation is related to vascular risk factors among patients with migraine, as migraine has been associated with higher prevalence of an unfavorable vascular risk profile (5,6). Continuing this hypothesis, one would expect that patients with migraine have a higher atherosclerotic load than individuals without migraine.

In this issue of Cephalalgia, Stam and colleagues investigate the association between migraine and the grade of prevalent atherosclerosis among 360 patients with migraine and 617 individuals without relevant headache disorders who participated in the population-based Erasmus Rucphen Family study (7). Atherosclerosis was quantified by intima media thickness, pulse wave velocity, and ankle-brachial index. Patients with migraine were more likely to be current smokers, to have a history of diabetes, to have lower high-density lipoprotein cholesterol, and to drink less alcohol. However, there was no association between migraine and any of the measures of atherosclerosis. There was also no difference between patients with migraine with aura and patients with migraine without aura. The study adds important aspects to the current evidence on the association between migraine and vascular health. In particular the study shows that, although migraineurs have increased frequency of some individual vascular risk factors, this does not necessarily translate to a higher load of atherosclerosis.

The association between migraine and individual vascular risk factors confirms many previous reports. For example, it has been reported in several population-based studies that migraine is associated with increased prevalence of individual vascular risk factors, such as smoking (5), diabetes (8), unfavorable cholesterol profile (9), and others. The lack of association between migraine and measures of atherosclerosis is in line with the results of the Women’s Ischemia Syndrome Evaluation study in which the coronaries of patients with migraine and controls were investigated by angiography among women presenting with symptoms suggestive of myocardial ischemia (10). In this study patients with migraine had even a lower load of atherosclerotic changes. However, contrary to the findings by Stam and colleagues, other studies have shown an association between migraine and impaired endothelial vasoreactivity or increased carotid artery media thickness (6,11), suggesting that migraine could well be a triggering factor for vascular pathologies that may eventually result in increased risk of cardiovascular disease events.

How can this apparent conflict between the studies be explained? Are the differences in findings of the various studies simply explained by study design and different target populations or by migraine assessments? There is one important aspect that is currently not considered when evaluating the interplay between migraine, vascular risk factors, and cardiovascular disease events: time. Migraine is an intermittent disorder with fluctuating frequencies during the lifespan and this change results in challenges to the classification of migraine in population-based settings (12). Repeated assessments of migraine and the vascular health status are necessary to definitely assess whether migraine leads to vascular pathologies during the lifespan that eventually increase the risk of cardiovascular disease events. It is possible that active migraine is not associated with atherosclerosis in the beginning, but that over time migraineurs have a faster development of vascular pathologies. It would be of particular interest to study the vascular health of individuals in whom the migraine has ‘stopped’.

Although only providing indirect evidence, the results by Stam and colleagues provide further evidence that atherosclerosis is an unlikely explanation of the migraine–cardiovascular disease association. Virtually all studies evaluating this association controlled for important vascular risk factors and there is increasing evidence that at least the association between migraine and ischemic stroke is limited to patients with migraine with aura who do not have an increased vascular risk profile (13,14).

What practical consequences should be taken? Assessment of vascular risk factors is important in patients with and without migraine. There is no evidence that patients with migraine have an additional benefit from antiplatelet therapy compared with individuals without migraine (15), so that migraine by itself should not be considered an indication for aspirin treatment in primary prevention of cardiovascular disease events.

In summary, the study by Stam and colleagues should reassure patients and their physicians that having an active migraine is not associated with a higher load of atherosclerosis. However, patients with migraine may still have a higher likelihood of vascular risk factors. Further research on the associations between migraine, the vascular system, and cardiovascular disease events should take the time factor into account to increase our understanding of why migraine is a marker of increased risk of vascular events.