Endothelial Function in Migraine With Aura
Endothelial Function in Migraine With Aura
Background An increased risk of ischemic stroke is repeatedly reported in young subjects with migraine with aura (MA). Such may be caused by changes in endothelial function. The present review evaluates current evidence on endothelial function in MA patients.
Methods A systematic search of electronic databases (Medline, Embase, Cochrane library) was performed, and a search in associated reference lists of identified studies was done.
Results In total, 27 studies met inclusion criteria for this review. Six studies assessed endothelial function by flow-mediated dilation; four reported no differences compared with healthy subjects, one study reported an increase and one study a decrease in migraineurs. Peripheral arterial tonometry was applied in one study where no changes were detected between groups. Likewise, applying venous occlusion plethysmography elicited comparable responses. Arterial function was investigated in six studies; increased augmentation index and decreased arterial distensibility were reported in migraineurs, whereas findings regarding pulse wave velocity were dissimilar. However, when investigating levels of endothelial progenitor cells, two studies reported reduced levels in migraineurs, and several studies on endothelial markers in the areas of inflammation, oxidative stress, and coagulation found increased endothelial activation in migraineurs, particularly in MA. One study, assessing cerebral endothelial function using transcranial Doppler sonography, reported lower cerebrovascular reactivity to L-arginine in the posterior cerebral arteries in migraineurs.
Conclusion Endothelial dysfunction appears not to be of importance in MA patients. However, the studies were few with a wide variety of techniques applied in small groups of patients. Endothelial biomarkers were increased in patients indicating a possible subtle change in the endothelium. Further investigations on larger groups of patients combining testing of endothelial dysfunction as well as biomarkers are warranted to identify whether or not endothelial changes may play a role in the increased risk of stroke in young MA patients.
Migraine is a common neurovascular disorder with a prevalence of 17.5% in women and 8.6% in men. It is characterized by attacks of moderate to severe headaches lasting from 4 to 72 hours, often unilateral and pulsating, and associated with nausea and/or photophobia and phonophobia. Approximately every third subject with migraine experiences aura, a phenomenon characterized by reversible transient focal neurological symptoms, typically preceding the headache.
Migraine, particularly migraine with aura (MA), has been associated with vascular diseases (Fig. 1): an increased risk of ischemic stroke has been reported in migraineurs, and this association was confirmed by three meta-analyses of observational studies, suggesting a twofold increased risk. Interestingly, two of the studies pinpointed the increased risk to women and MA and also that the link between MA and ischemic stroke was independent of traditional risk factors. Moreover, results from a prospective cohort study indicated an association between migraine and hemorrhagic stroke in the subgroup of women with MA. A meta-analysis showed a small, but significant increase in risk of hemorrhagic stroke in migraineurs in general, with no difference between MA and migraine without aura (MO). MA was recently suggested to associate with white matter lesions, and a large prospective study indicated an association between cardiac events and women with MA.
(Enlarge Image)
Figure 1.
Evidence on the association between migraine with aura (MA) and the risk of vascular diseases.
The mechanisms of the seemingly higher risk of vascular diseases, in particular ischemic stroke, in subjects with MA are currently unknown. Several explanations have been proposed for the association of vascular diseases and MA, one being increased endothelial dysfunction. Mounting evidence imply that migraine is linked to endothelial dysfunction, as both a cause and a consequence. Endothelial dysfunction, referred to as the ultimate risk of the risk factors, is a pathological condition characterized by impairment of endothelium-dependent vasodilation due to a decrease in the bioavailability of vasodilating factors and an increase in endothelium-derived vasoconstrictors. Another feature is the induction of endothelial activation characterized by a proinflammatory and procoagulatory milieu, which favors all states of atherogenesis and vascular diseases. The endothelial function has been repeatedly studied in subjects with MA, however, with dissimilar conclusions. The aim of the present systematic review is to evaluate the published evidence on endothelial function in subjects with MA. If endothelial function is affected, it may be a target for identifying subjects at risk and preventing stroke in this particular group of patients who may experience stroke at a young age. A meta-analysis is not relevant due to the diversity of the studies included: in particular, the variations in applied methodology, patient characteristics as well as methods applied and outcome measures. Performing quantitative, statistical analysis on these diverse data would not be optimal.
Abstract and Introduction
Abstract
Background An increased risk of ischemic stroke is repeatedly reported in young subjects with migraine with aura (MA). Such may be caused by changes in endothelial function. The present review evaluates current evidence on endothelial function in MA patients.
Methods A systematic search of electronic databases (Medline, Embase, Cochrane library) was performed, and a search in associated reference lists of identified studies was done.
Results In total, 27 studies met inclusion criteria for this review. Six studies assessed endothelial function by flow-mediated dilation; four reported no differences compared with healthy subjects, one study reported an increase and one study a decrease in migraineurs. Peripheral arterial tonometry was applied in one study where no changes were detected between groups. Likewise, applying venous occlusion plethysmography elicited comparable responses. Arterial function was investigated in six studies; increased augmentation index and decreased arterial distensibility were reported in migraineurs, whereas findings regarding pulse wave velocity were dissimilar. However, when investigating levels of endothelial progenitor cells, two studies reported reduced levels in migraineurs, and several studies on endothelial markers in the areas of inflammation, oxidative stress, and coagulation found increased endothelial activation in migraineurs, particularly in MA. One study, assessing cerebral endothelial function using transcranial Doppler sonography, reported lower cerebrovascular reactivity to L-arginine in the posterior cerebral arteries in migraineurs.
Conclusion Endothelial dysfunction appears not to be of importance in MA patients. However, the studies were few with a wide variety of techniques applied in small groups of patients. Endothelial biomarkers were increased in patients indicating a possible subtle change in the endothelium. Further investigations on larger groups of patients combining testing of endothelial dysfunction as well as biomarkers are warranted to identify whether or not endothelial changes may play a role in the increased risk of stroke in young MA patients.
Introduction
Migraine is a common neurovascular disorder with a prevalence of 17.5% in women and 8.6% in men. It is characterized by attacks of moderate to severe headaches lasting from 4 to 72 hours, often unilateral and pulsating, and associated with nausea and/or photophobia and phonophobia. Approximately every third subject with migraine experiences aura, a phenomenon characterized by reversible transient focal neurological symptoms, typically preceding the headache.
Migraine, particularly migraine with aura (MA), has been associated with vascular diseases (Fig. 1): an increased risk of ischemic stroke has been reported in migraineurs, and this association was confirmed by three meta-analyses of observational studies, suggesting a twofold increased risk. Interestingly, two of the studies pinpointed the increased risk to women and MA and also that the link between MA and ischemic stroke was independent of traditional risk factors. Moreover, results from a prospective cohort study indicated an association between migraine and hemorrhagic stroke in the subgroup of women with MA. A meta-analysis showed a small, but significant increase in risk of hemorrhagic stroke in migraineurs in general, with no difference between MA and migraine without aura (MO). MA was recently suggested to associate with white matter lesions, and a large prospective study indicated an association between cardiac events and women with MA.
(Enlarge Image)
Figure 1.
Evidence on the association between migraine with aura (MA) and the risk of vascular diseases.
The mechanisms of the seemingly higher risk of vascular diseases, in particular ischemic stroke, in subjects with MA are currently unknown. Several explanations have been proposed for the association of vascular diseases and MA, one being increased endothelial dysfunction. Mounting evidence imply that migraine is linked to endothelial dysfunction, as both a cause and a consequence. Endothelial dysfunction, referred to as the ultimate risk of the risk factors, is a pathological condition characterized by impairment of endothelium-dependent vasodilation due to a decrease in the bioavailability of vasodilating factors and an increase in endothelium-derived vasoconstrictors. Another feature is the induction of endothelial activation characterized by a proinflammatory and procoagulatory milieu, which favors all states of atherogenesis and vascular diseases. The endothelial function has been repeatedly studied in subjects with MA, however, with dissimilar conclusions. The aim of the present systematic review is to evaluate the published evidence on endothelial function in subjects with MA. If endothelial function is affected, it may be a target for identifying subjects at risk and preventing stroke in this particular group of patients who may experience stroke at a young age. A meta-analysis is not relevant due to the diversity of the studies included: in particular, the variations in applied methodology, patient characteristics as well as methods applied and outcome measures. Performing quantitative, statistical analysis on these diverse data would not be optimal.
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