Migraine and vascular disease

The association between migraine and vascular disease has long been recognised, says David Kernick.

Scan of a patient's brain during a migraine; grey area (lower left) shows low brain activity (Photograph: SPL)
Scan of a patient's brain during a migraine; grey area (lower left) shows low brain activity (Photograph: SPL)

Approximately 15 per cent of the population suffer with migraine. The pathogenesis of migraine is poorly understood but the condition is viewed as an inherited disorder of the brain and vascular mechanisms such as endothelial dysfunction, hypercoagulability and vascular reactivity have all been implemented in the disease process.1

A third of sufferers will have migraine with aura. An aura is a cortical wave of spreading depression lasting for less than an hour that usually precedes the headache phase and can be a positive or negative, sensory or motor phenomenon. Visual aura is the most common.

What does the evidence tell us?
An association between migraine and vascular disease has been recognised for some time. In all studies, the increased risk has been observed with migraine with aura and migraineurs without aura do not seem to be at risk of vascular disease.

A relationship between ischaemic stroke and migraine has long been recognised but more recently an association between migraine and hemorrhagic stroke has been confirmed.2

The population 10-year risk of stroke under 55 years of age is 2 per cent3 and the risk of stroke in migraineurs with aura is approximately doubled. The absolute increase in risk is therefore quite small.

For cardiovascular disease risk, previous research has been equivocal but a recent study has reported an increase in risk of approximately 1.3.2

As with stroke, migrainuers without aura are not at increased risk of cardiovascular disease.

What is an aura?
  • A reversible motor, sensory or other neurological symptom that is recurrent or stereotyped.
  • Develops gradually over up to 20 minutes and lasts usually less than 60 minutes.
  • Characterised by evolution of the symptoms due to a wave of spreading depression.
  • Can be simple (positive or negative) or complex.
  • Mainly involves the cortex but can involve the brain stem.
  • Precedes the headache but can occur at any time during the headache phase and can be experienced without headache.
  • Is often confused with the prodrome, a psychological or neurological phenomenon that can occur up to 48 hours before the migraine.
  • Visual aura is the most common followed by parasthesia.
  • Most symptoms occur in 18 per cent of patients with aura.

Problems with the data
There are a number of problems with the research data and many potential confounding factors. For example, questionnaires may not accurately diagnose either migraine or migraine with aura and the aura pattern may change over time. This makes classification difficult in large studies. In addition, many of the drugs used to treat migraine, such as 5HT1 agonists, may increase the risk of cardiovascular disease.

The nature of these relationships is not known and may not be directly causal. For example, in comparison with controls, migraine with aura is associated with significantly increased risk for hypertension and hyperlipidaemia.4 An intriguing hypothesis is the relationship between migraineurs with aura and an associated high level of cardiac septal defects that could cause stroke.

Neurological accompaniments of migraine also confuse the picture. For example, stroke can be associated with migraine-type headache and auras, such as hemiplegic or basilar aura, can mimic stroke and can occur in the absence of headache.

Identifying whether the treatment of migraine with aura reduces vascular events is fraught with methodological problems. For example, RCTs would be unethical and the treatment of choice for migraine is a beta-blocker which itself will have beneficial effects on vascular outcomes through reduction of BP.

What to tell the patient?
Most patients are well informed and may bring this issue to the attention of the practitioner. They can be reassured that the absolute risk is quite small. The more difficult question is whether this information should be discussed spontaneously with the patient, particularly as we have no information as to whether treating the condition will reduce risk. Ultimately, life in primary care is a continuum of risk that the GP manages on behalf of their patient.

For example, there is a 1.3 times greater risk of stroke with psychosocial stress and a similar risk with depression.5 These risks are rarely discussed.

In practice, management should focus on the identification and management of risk factors that are reversible and well established such as smoking, diabetes, obesity and BP.

Perhaps most important of all is the diagnosis and adequate management of migraine. The majority of patients with headache that present to their GP do not achieve a diagnostic threshold and when migraine is diagnosed, treatment is often inadequate, leading to high levels of morbidity.6

Key points
  • Migraine with aura increases the risk of stroke and cardiovascular disease but the mechanism is unknown.
  • This risk is not associated with migraine without aura.
  • The risk, particularly for stroke, is further increased in young women who smoke and are on the pill.
  • Whether adequate treatment of migraine with aura reduces this risk is unknown.
  • David Kernick is a GP with a special interest in headache and RCGP headache champion
References
1. Silberstein S. Migraine. Lancet 2004; 363: 381-91.

2. Berger K, Evers S. Migraine with aura and the risk of increased mortality. BMJ 2010; 341: c4410.

3. D'Agostino R, Wolf P, Bellinger A, et al. Stroke risk profile: the Framingham study. Stroke 1994; 25: 40-3.

4. Scher A, Terwind LG, Picave T et al. Cardiovascular risk factors and migraine. The GEM population based study. Neurology 2005; 64: 614-20.

5. O'Donnell M, Xavier D, Liu L et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries: a case control study. Lancet 2010; 376: 112-23.

6. Kernick D, Stapley S, Hamilton W. GPs classification of headache: is primary headache under diagnosed? Br J Gen Pract 2008; 58: 102-4.

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