Rabe_EU Neurology 09/03/2010 12:41 Page 93
Migraine and Vascular Disease
The risk of myocardial infarction in migraineurs was not increased. promotes endothelial dysfunction. Endothelial dysfunction is
Similar findings were presented by Rose et al.,
4
who examined associated with an increased rate of cerebro- and cardiovascular
12,409 participants from the Atherosclerosis Risk in Communities ischaemic events.
26
Further evidence of vascular dysfunction
Study. Participants with headaches, particularly if accompanied by comes from Vanmolkot et al.,
27
who found that young migraineurs
auras, had an increased risk of Rose angina. The authors concluded (under 35 years of age) have a decreased diameter and compliance
that the association of migraine with Rose angina is not related to of peripheral arteries.
coronary heart disease because the risk of cardiovascular disease
was not increased. In addition to vascular dysfunction, coagulation abnormalities
28,29
and platelet hyperaggregability
16
have been observed in migraineurs,
Recently, Kurth et al. presented two large prospective cohort which might lead to a higher incidence of thrombotic events. A recently
studies in women
3
and men
6
that evaluated the relationship published population-based study showed that migraineurs had a higher
between migraine and cardiovascular disease. In the Women’s lifetime history of venous thromboembolism than non-migraineurs.
30
Health Study, 27,840 participants 45 years of age or older were
followed for up to 10 years. Migraineurs with aura presented a Finally, migraine and ischaemic events might be linked genetically.
higher risk of myocardial infarction (multivariable-adjusted hazard Migraine is a symptom in genetic diseases such as cerebral
ratio [HR] 2.08, 95% CI 1.30–3.31), coronary revascularisation (HR autosomal dominant arteriopathy with subcortical infarcts and
1.74, 95% CI 1.23–2.46) and angina (HR 1.71, 95% CI 1.16–2.53) leukoencephalopathy (CADASIL)
31
and mitochondrial myopathy,
compared with women without migraine. In the Physicians’ Health encephalopathy, lactacidosis and stroke (MELAS).
32
Genetic factors
Study,
16
20,084 men were followed. Men with migraine had a that might add to the risk of cardiovascular disease have also been
statistically higher risk of myocardial infarction (HR 1.42, 95% CI linked to migraine.
33,34
The angiotensin-converting enzyme gene
1.15–1.77) but not coronary revascularisation or angina compared deletion polymorphism (ACE-DD) seems to be associated with an
with participants without migraine. As described earlier, the same increased frequency of migraine attacks,
33
and the methylene-
population did not show an increased risk of stroke. tetrahydrofolate reductase (MTHFR) C677-TT polymorphism is
associated with an increased risk of migraine with aura.
34
Pathophysiology
Pathophysiological Mechanisms Underlying Characteristics of the Pathophysiology
Cardio- and Cerebrovascular Events Leading to Stroke
Several studies found an unfavourable cardiovascular risk profile While cardiovascular risk factors and biological mechanisms lead to
in patients with migraine. Participants in the Genetic Epidemiology a higher incidence of ischaemic events in the brain and the heart,
of Migraine study with migraine with aura presented more other findings in migraineurs explain only the increased risk of
often with an unfavourable cholesterol profile, arterial cerebral events. Clinically silent brain infarcts and WMLs are
hypertension and a history of smoking.
17
Their Framingham risk observed more frequently in migraineurs than in people without
score for coronary heart disease was more likely to be increased. headache.
35–38
The risk of WMLs is higher in patients with migraine
Kurth et al.
11
found an elevated predicted 10-year risk of coronary with aura than in those without aura, and increases in line with the
heart disease (according to the Framingham risk score) in frequency of attacks.
20
Most often, ischaemic lesions are localised
participants with migraine (with and without aura). The risk of in the posterior circulation territory.
20
stroke or cardiac events in migraineurs is higher if participants use
oral contraceptives, smoke,
12,18
have a high blood pressure
6,19
or Other studies indicate an association between migraine, particularly
have elevated cholesterol levels.
6
migraine with aura, and patent foramen ovale (PFO).
39–41
Migraine-
triggering vasoactive components, which are removed during
However, migraine itself bears the risk of cardiovascular events. passage through the lungs, could reach the cerebral circulation via
Most trials report an increased risk of cardiovascular events even a PFO. As observed in migraineurs, ischaemic infarctions due to
after correcting for cardiovascular risk factors.
3,6,7,9,10,18
Accordingly, paradoxical emboli tend to occur in the posterior circulation.
42
The
the risk of cardiovascular events is more increased in migraineurs cortical spreading depression might be triggered through focal
with a low cardiovascular risk profile
3,9
and in younger ischemia. It was observed that a PFO closure improved the
participants
3,6,10
compared with controls. Additionally, migraine- frequency and severity of migraine attacks.
43,44
specific drugs might produce a higher morbidity due to vascular
events. Migraineurs frequently use triptans or ergots to medicate Against this background, the Migraine Intervention with STARflex
®
their headache. Patients using ergots have a higher risk of white Technology (MIST) trial was conducted.
45
Participants with migraine
matter lesions (WMLs)
20
and ischaemic events.
21
However, an with aura who were refractory to at least two prophylactic
increased risk of cardio- and cerebrovascular events could not be medications and had frequent attacks were randomised to PFO
shown for triptans.
20–22
closure or a sham procedure. This trial could not support earlier
findings. Only when removing two outliers was the frequency
Several biological mechanisms are discussed through which of migraine attacks reduced after PFO closure compared with a
migraine might lead to cardiovascular events. Migraine might sham procedure.
be a systemic disorder that affects the vasculature. Endothelial
dysfunction is a potential mechanism. During a migraine In summary, the possible explanations for why migraine and PFO
attack, levels of von Willebrand factor, a serum marker of frequently occur together are insufficient. The disposition for both
endothelial dysfunction, increase.
23,24
People with migraine with disorders could be inherited simultaneously and may not have a
aura might have a vulnerability to oxidative stress,
25
which causal link.
EUROPEAN NEUROLOGICAL REVIEW 93
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