Migraine headache, particularly migraine with aura, is associated with increased risk for cardiovascular disease and cerebrovascular events, including ischemic stroke. In light of the high prevalence of migraine headache, this association should be further investigated, according to a review published in the Journal of the American Heart Association.

Other than the characteristic headache, migraine may be associated with transient focal neurology symptoms (eg, aura) that usually persist for less than an hour. There is a wide inter-individual and intra-individual variability in the frequency of migraine attacks. Migraine is most common in women aged 25 to 55 years, and the prevalence decreases after the fifth decade of life.

There are several possible mechanisms for the increased risk for cardiovascular and cerebrovascular disease in patients with migraine, including higher prevalence of hypertension and hyperlipidemia, generalized endothelial dysfunction and increased platelet aggregation, higher prevalence of patent foramen ovale (PFO), and the effect of medications used to treat these patients.

Previous studies have reported gender differences in migraine characteristics, as the disease is more prevalent and frequently more severe in women. It is believed that fluctuations in hormone levels, particularly estrogen, may be responsible for these gender differences.

Many studies have reported an association between migraine and cardiovascular and cerebrovascular disease, with a more robust association in cases of migraine with aura. There are data associating migraine with aura with an increased risk for ischemic stroke, myocardial infarction, cardiovascular mortality, as well as venous thromboembolism and peripheral artery disease.

As noted, PFO may be more common in patients with migraine. Several studies have suggested that closure of PFO may be beneficial and reduce migraine attack frequency. However, as this was not the primary outcome of the studies, routine PFO closure for migraine should not be recommended at this point.

While there are many studies reporting an association between migraine and cardiovascular and cerebrovascular events, the rate of events in all these studies was low. On the other hand, due to the high prevalence of migraine worldwide, this still translates into a substantial increase in population risk.

At this point, there are no established recommendations aimed at reducing cardiovascular risk in patients with migraine. Evidence of potential benefit of anti-platelet, beta-blocker, and statin therapy in patients with migraine are lacking. Moreover, limited data are available on the effect of controlling migraine symptoms on cardiovascular events.

While triptans have not been shown to increase cardiovascular risk in patients with migraine, nonsteroidal anti-inflammatory drugs use should be limited to acute migraine episodes, as chronic use may be associated with increased cardiovascular risk.

Patients with migraine should be counseled about a healthy lifestyle, including regular physical activity, smoking cessation, blood pressure control, and weight loss.

“To date, there has been no established therapy to lower cardiovascular risk among women with migraine. Physicians should inquire about migraine history when assessing the cardiovascular risk of women,” concluded the researchers.

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New drugs against migraines block the neuropeptide αCGRP, which leads to vasodilation on the meninges. The same peptide that is formed in the muscles during physical activity protects the heart – which is vital for people with chronic high blood pressure.

The novel migraine prophylaxis is likely to be dangerous for them, as researchers at the University of Zurich have shown in mice. The neuropeptide αCGRP or α Calcitonin Gene-Related Peptide, works in two different ways. Directly at the point of release of the nerve cells – for example on the meninges – it leads to inflammation and dilates the blood vessels, which can cause migraine attacks. It affects the heart quite differently, as a team of researchers from the University of Zurich (UZH) has now found out.

Negative effect on the meninges, more positive on heart

As the scientists show from studies with mice, αCGRP is also released from the working skeletal muscles. It gets from the muscle to the heart via blood, where it inhibits the disease-causing changes in the heart caused by chronic high blood pressure.

“It’s the same with humans as with the mouse: physical activity and exercise increase the blood plasma level of αCGRP, which has a positive effect on the heart if the blood pressure is increased,” says study leader Johannes Vogel, professor at the Institute of Veterinary Physiology at UZH.

Therapy option for certain hypertensive patients

In their work, the researchers compared normal mice to those with chronic high blood pressure, who were either physically passive or repeatedly walked voluntarily. It was shown that normal concentrations of αCGRP in the blood plasma are essential for survival and that the positive effects of physical activity on the heart depend on the peptide.

ΑCGRP also protects the heart regardless of its hypotensive properties in higher doses. “In the future, substances that activate the release of αCGRP could be used in patients with high blood pressure who can only be physically very limited, or for whom antihypertensive drugs do not work or do little,” explains Johannes Vogel.

Beware of migraine medication and chronic high blood pressure

The research also revealed another result: In mice with chronic high blood pressure, long-term administration of αCGRP blockers led to life-threatening cardiac dysfunction. Medications that specifically block the neuropeptide have recently been used for migraine prophylaxis. Since the neuropeptide αCGRP is very similar from zebrafish to humans, it must be a central biological mechanism that works in a comparable way in many organisms.

According to the cardiovascular specialist Vogel, the results are therefore also relevant for humans: “αCGRP blockers should only be used to prevent migraine if the patient’s blood pressure is checked regularly.

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