Clarifying Cardiovascular Risk in Migraine

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The hormonal mechanisms that protect premenopausal women from CV events are the same ones that lead to a much higher rate of migraine in women.
The hormonal mechanisms that protect premenopausal women from CV events are the same ones that lead to a much higher rate of migraine in women.

Increased rates of cardiovascular (CV) events, particularly stroke, in people with migraine have long been observed, although the significance of this link is not well understood. Using the Framingham Cohort to quantify risks for future CV events, the American Migraine Prevalence and Prevention (AMPP) study confirmed that these risks do increase with age in both men and women, with the highest risks seen in people older than 60, aligning with the general population.1

“Persons with migraine have a slightly increased risk for cardiovascular events compared with those who don't have migraine, and this is more pronounced in the subgroup having migraine with aura,” Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache and chief medical officer at the New England Institute for Clinical Research and Ki Clinical Research in Stamford, Connecticut told Neurology Advisor. He noted that individuals who are diagnosed with migraine are advised to actively take steps to minimize other cardiovascular risk. “Exercise, healthy eating, controlling blood pressure and sugar if necessary, refraining from smoking, low to moderate alcohol intake, good sleep hygiene, and stress reduction are all important.  Women with migraine wishing to start birth control should consult their doctor first,” Dr McAllister advised.

AMPP study co-auther Dawn C. Buse, PhD, associate professor of neurology at Albert Einstein College of Medicine of Yeshiva University, explained how CV risk affects men and women with migraine differently. “The risk of cardiovascular events [also] increases with age as well as with body mass index, family history, and other variables. Cardiovascular events are more prevalent among men compared with women at each age strata; however, cardiovascular disease is both under-recognized and undertreated in women. Heart disease is the leading killer of women; more than 1 in 3 adult women has some form of cardiovascular disease. So while the magnitude of the cardiovascular risk remains lower for women at the level of the individual patient, it is important at a population level since migraine is highly prevalent, particularly in women,” she said.

Although the main risks associated with migraine involve ischemic and hemorrhagic stroke, new evidence from a 2018 population study by Adelborg, et al2 that included more than 51,000 patients from a Danish patient registry found that risks for venous thromboembolism and atrial fibrillation (but not heart failure or peripheral artery disease) were also higher. This study, published in the British Journal of Medicine, triggered an editorial by Kurth, et al,3 which posed the question of whether or not cardiovascular risks associated with migraine are due to the headache manifestations affecting blood flow to the brain, or whether there is an underlying shared etiology.

The migraine-CVD connection may be — at least in part — hormonally mediated. The hormonal mechanisms that protect premenopausal women from CV events are the same mechanisms that lead to a much higher rate of migraine in women (3:1 ratio).1

“For women, the risk of CVD increases after menopause. One reason may be the natural decline in estrogen that occurs after menopause,” Dr Buse said, noting that diminishing circulating levels of estrogen contribute to a higher risk for CV events through multiple mechanisms. “Estrogen helps keep the blood vessels flexible through a positive effect on the inner layer of the artery wall. There are likely other influences that increase cardiovascular risk after menopause. Blood pressure, LDL cholesterol, and triglyceride levels tend to increase, while HDL cholesterol levels tend to decline after menopause, leading to increased cardiovascular risk. An overall increase in heart attacks among women is seen about 10 years after menopause,” she said.

Several medications potentially increase the risks for CV events as well, as both ergot-based drugs and triptans are contraindicated in patients with high CVD risk, including a previous history of a CV event. Despite this, Dr McAllister stated that migraine-specific triptans are generally safe for most patients with migraines, with the exception of patients with uncontrolled CV risk factors. “Non-steroidal anti-inflammatory drugs [NSAIDs], used infrequently, are also felt to be safe, but very frequent or daily NSAID use has been associated with cardiovascular events,” he added.

Although a general trend was observed in the AMPP study toward increased risk for CV events in people older than 60, current recommendations for triptan use do not address this population.1 “There are no specific age guidelines or upper age limits for triptan use,” Dr Buse said, “however, people over age 50 face an increased risk of cardiovascular disease, and triptans and ergot alkaloids are contraindicated in people with existing cardiovascular disease, among patients with migraine and uncontrollable risk factors for cardiovascular disease and cardiovascular event history such as myocardial infarction.” She noted that in cases in which a patient has been using a triptan therapy for some time, it is wise to reassess cardiovascular history and health to determine whether triptans are still a safe choice for them. 

References

  1. Lipton RB, Reed ML, Kurth T, Fanning KM, Buse DC. Framingham-based cardiovascular risk estimates among people with episodic migraine in the US population: Results from the American migraine prevalence and prevention (AMPP) study. Headache. 2017;57:1507-1521.
  2. Adelborg K, Szépligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular disease: Danish population-based matched cohort study. BMJ. 2018;360:k96.
  3. Kurth T, Rohman JL, Shapiro RE. Migraine and risk of cardiovascular disease: action to reduce risk is long overdue. BMJ. 2018;360:k275.
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