The Link between Migraine and Heart Disease

In 2006, a study focusing on the benefits of aspirin and vitamins for the prevention of cardiovascular disease (CVD) and cancer in women discovered something that would begin a new debate among headache specialists. The Women’s Health Study revealed that women with migraine with aura have a significantly higher risk of developing CVD. More trials found that male migraineurs were also at risk. These findings added to concerns raised by earlier studies that found that migraineurs with aura had a higher risk of stroke.

Because new findings regarding migraine and heart health are emerging rapidly, NHF Head Lines recently interviewed Glen D. Solomon, MD, FACP, to better understand the risks, who is affected, and what migraineurs can do to protect themselves. Dr. Solomon is the Chair of the Department of Medicine at Advocate Lutheran General Hospital in Park Ridge, Illinois, and Professor and Vice Chair of the Department of Medicine at the Rosalind Franklin University of Medicine and Science/Chicago Medical School.

What is the increased risk for cardiovascular disease?

In 1993, more than 40,000 women health professionals throughout the U.S. were enrolled in the Women’s Health Study. Just over 18% of them had migraine. Of those, 40% reported having aura. The women, whose average age was 45 when the study began, were followed for ten years.

”The results of the study were rather striking,” says Dr. Solomon, ”in that women who have migraine with aura have a significantly increased risk of having major CVD. They have a two-fold risk of having myocardial infarction (heart attack), an almost two-fold risk of having ischemic stroke, and a more than two-fold risk of dying from CVD.”¹

The Physician’s Health Study, which followed over 20,000 male health professionals over 15 years, had similar results. Just over 7% of the men had migraine; combined, they had a 24% increased risk for CVD.² Though the study didn’t differentiate men who had migraine with aura from those who didn’t, researchers believe that, as with women, the increased risk is concentrated in migraineurs with aura.
However, before readers panic, Dr. Solomon says, ”It’s important to put this into context. We’re looking at women who may be at lower risk than men for CVD.”

He also points out that people with migraine who don’t have aura (approximately 80% of migraineurs) have the same risk for heart disease as people without migraine. The study suggests, then, that there is something about aura that puts people who experience the flashing lights, tingling sensations, or other migraine-warning symptoms at a higher risk of developing cardiovascular problems.

Because migraine is such a common disease, the findings still do affect a large number of people. Eighteen percent of women (and 6% of men) in the U.S. have migraine and 20% of them have migraine with aura. ”So roughly one in ten women in the United States is at increased risk of heart disease because of migraine with aura,” says Dr. Solomon. ”There are a lot of people who are now at an increased risk who never thought they were at increased risk of heart disease.”

Why do individuals with migraine with aura have an increased risk?

”This is a place where we just don’t know the answer yet,” Dr. Solomon admits.
It’s possible that other risk factors that people with migraine tend to have play a role. Migraineurs are more likely to smoke, for example. They’re less likely to drink alcohol or eat chocolate, because both can trigger migraine attacksÅ|it is now believed that red wine and dark chocolate may be good for the heart. ”But these alone don’t explain it, because migraineurs without aura don’t have the increased risk,” says Dr. Solomon.

Perhaps, then, it’s because people with migraine with aura have their own set of risk factors. They tend to have elevated cholesterol and blood pressure, which are likely due to a genetic predisposition. People with migraine with aura also tend to have a higher use of oral contraceptives, which may contribute to their risk. ”But again,” says Dr. Solomon, ”I don’t think these factors alone are enough.”

Rather, he believes that the findings suggest that there is a link between the aura and the vascular system itself. ”Either it is directly related to the change in the brain that causes aura, thereby having a direct effect on blood vessels (such as affecting vascular inflammation),” explained Dr. Solomon, ”or it is genetically linked to the gene that affects vascular disease. That’s the only way you can realistically explain this.”

How can migraine sufferers keep their hearts safe?

”The bottom line is that if you are a patient who has migraine with aura, you need to consider this as one more risk factor for CVD and be diligent about reducing those risk factors that you can control,” says Dr. Solomon. In particular, he recommends monitoring blood pressure and cholesterol levels regularly and he’s adamant that people with migraine with aura should not smoke.

”It also means that you should exercise regularly and watch your weight, all of the good, healthy things that we tell people to protect their heart. You can’t change the fact that you have migraine with aura, but you can change your weight, your blood pressure and your cholesterol, and you can decide not to smoke. That’s not bad advice for everybody in the world.”

Migraineurs also have increased risk for stroke

Perhaps not surprisingly, the elevated risk for stroke impacts a similar population and calls for similar strategies. Studies have found that the risk of stroke is doubled for migraineurs. The risk is particularly striking for young women with aura. ”The risk of stroke is probably three fold-greater in young women with migraine as opposed to women without migraine,” says Dr. Solomon.

Nevertheless, stroke is not something that migraineurs should generally be worrying about. The risk of stroke is very low in young women, ”so three times very low is still very low.” The absolute risk for stroke is 19 per 100,000 women migraineurs per year compared with 6 per 100,000 for women without migraine. ³

Factors that increase a woman’s risk are having migraine with aura, frequent migraines (more than 12 times per year), having migraine attacks for more than 12 years, smoking and using oral contraceptives. Because, once again, migraine is not a factor that people can control, Dr. Solomon advises patients to focus on the issues they can control (blood pressure, cholesterol, etc.), with the addition of avoiding oral contraceptives.

”The incidence of stroke for a 40-year-old woman with migraine with aura who is taking oral contraceptives goes up to 139 per 100,000 women per year. That’s a 12-fold greater risk. Women who have migraine with aura should probably look for another birth control method and definitely should not smoke.” Migraineurs who smoke face a 10-fold increased risk of stroke.

The good news is that the risk of stroke actually goes away as people get older and there is no association between migraine and stroke in the elderly. After age 40, a migraineur’s risk of having a stroke is the same as for the regular population. And because the people at the most risk of stroke are typically over 40, the elevated stroke risk turns out to not be of much concern.

Could migraine be caused by a heart problem?

Both cardiologists and neurologists have been interested in the relationship between a common heart defect and migraine since 2000. That was when Peter Wilmhurst, MD, and his colleagues reported that fixing the defect, known as patent formamen ovale (or PFO), serendipitously resulted in significant reduction or even cessation of migraines. All of the patients in the report, which was published in The Lancet, had suffered a neurological event, such as a stroke, which was why they had the surgery. It so happened that a number of them also suffered from migraine.

A PFO is a natural opening between the upper chambers of the heart that usually closes shortly after birth. In about 25% of humans, however, the flap, for unknown reasons, does not entirely scar shut, leaving a passage or tunnel between the right and left atria. Even in patients with a patent, or open, foramen ovale, there is typically little blood passage from the right side to the left side of the heart.
However, during hard coughing or sneezing, the pressure on the right side can increase and open the flap, sending unfiltered and unoxygenated blood directly into the left atrium of the heart and then out to the body. Strokes can occur when a clot from the veins, which would normally be filtered out by the lungs, passes directly to the left side of the heart and into the brain. For that reason, some stroke patients have undergone the procedure to close the PFO.

In Dr. Wilmhurst’s report, 18 of 21 patients who underwent PFO closure for stroke or decompression illness reported either complete disappearance or significant reduction in the frequency of their migraine attacks. Studies done since then have had similar results. Up to 60% of migraine patients reported complete resolution of their migraine, and a significant portion of other patients reported a reduction in migraine frequency.

Studies have also found that PFOs are more common in migraine sufferers, especially those with aura, than in the general public. The defect was found in 44% of migraineurs versus 16% of controls. PFO is associated with a 4-fold increased likelihood of migraine with aura.

Given these findings, a number of researchers have begun larger trials to ascertain whether closing a PFO is a viable and safe alternative for treating migraine. While the studies hold out some hope for patients with migraines who don’t respond to other treatments, Dr. Solomon, like many headache specialists, is not yet ready to embrace the procedure.

”PFOs are still really an unanswered question,” he says. ”We have more questions than we have answers. None of the studies that have been published so far have been randomized, controlled, clinical trials, though studies of the sort are underway. It’s hard to interpret the data that we do have other than to say that large percentages of patients have seen significant improvement in their migraines when they have had their PFOs closed.”

But Dr. Solomon is concerned that the surgery is not without risk. ”It’s an invasive procedure that requires cardiac catheterization, and use of aspirin and clopidogrel (to prevent blood clots) for at least three months.” Patients with nickel allergies have also been found to be more likely to have new or worsening migraine after the procedure.

”This is one of those things that patients will find very appealing—an operation that will take away migraine,” worries Dr. Solomon. ”But at this point our data just doesn’t quite support it yet. We just don’t have controlled clinical trials to show that the benefits outweigh the risks. I think this is very promising, but based on the data that we have today, I don’t think we can legitimately recommend this to our patients.”

Could migraine medications be increasing the risks?

The issue of whether triptans or nonsteroidal anti-inflammatory medications (NSAIDs) can carry cardiovascular risks has also been raised, particularly since it was found that Vioxx(R) and other cox-2 inhibitors may increase the risk of heart attack. So do migraineurs need to be concerned about the medications they take, too?

Most people can rest easy about taking the triptan medications for relief of migraine, says Dr. Solomon. Patients who already have cardiovascular issues are advised not to take triptans. For everyone else, no association has been found between triptans and stroke, heart attacks, ischemic heart disease, or cardiovascular mortality.

”What we see from the data is that when triptans are used appropriately in people with little or no risk for cardiovascular disease, they appear to be very safe from a cardiovascular standpoint and not a cause for increased risk,” says Dr. Solomon.

Dr. Solomon does sound a note of caution regarding taking triptans later in life, when people’s cardiovascular risks typically rise. ”We don’t know the long-term risks of any of these drugs yet because they haven’t been out long enough. We need to reassess whether patients should remain candidates for these drugs as they turn 50 and enter high-risk groups for cardiovascular disease. Just because they’ve been on these drugs in the past doesn’t mean we don’t need to take a step back.”

As for NSAIDS, there may be some risk with long-term use. ”It was said that NSAIDS were a safer alternative to patients with triptan risk factors,” says Dr. Solomon. ”Now there’s some evidence that NSAIDs carry the same risk.”

Dr. Solomon points out that ”all NSAIDs are not the same.” He advises choosing wisely and adds that, from a cardiovascular standpoint, naproxen appears to be the safest.

Don’t worry, but do make healthy choices

It turns out that, despite the media coverage and burgeoning studies, most migraine sufferers are ”really pretty safe.” The bottom line, says Dr. Solomon, is that ”like everyone else walking the street, we all have to be concerned about heart disease. We all should exercise and eat right and get our blood pressure checked.

”But people should not live in worry of having a stroke or heart attack. We have never seen an epidemic of cardiovascular disease or stroke in this population. The clinical reality is most people with migraine will never have to be worried. They should not take this on as a unique burden; rather, they should factor it into their overall healthy lifestyle issues.”

1 Kurth T, et al, JAMA, 2006; 296:283-291
2 Kurth T, et al, Archives of Internal Medicine 2007; 167:795-801
3 Tietjen G., CNS Drugs 2005; 19(8):683-692

—Lesley Reed

Help for Pregnancy-Induced Headaches
Q. I am 15 weeks pregnant with my first child and have been having severe headaches almost every day throughout my pregnancy. On the two headache-free days I’ve had, my head was tender and sore. I did not experience headaches on a regular basis prior to getting pregnant.

The pain is on my left side, often in my left eye, and travels down the left side of my head to the base of my head and neck. Sometimes I wake up with these headaches and they last all day. The headaches start as a very light pain, but the pain quickly increases and can last several hours. Sound, light and even smell, along with motion, intensify the pain. I have looked for triggers for these headaches, but cannot find any obvious ones.

These headaches make me very tired and irritable and incapacitate me. I only find any sort of relief by lying perfectly still in a pitch black room with no noise or smells.

Concerned by these headaches, I called my OB/GYN and asked for advice. She referred me to a neurologist, who diagnosed me with migraines induced by pregnancy and prescribed Inderal(R). He also scheduled trigger point injections for later this month. Being pregnant, I am concerned about medications and treatments, so I read all I could find on Inderal and discovered that it is a class C pregnancy drug. I am concerned by what I read, but both my neurologist and my OB/GYN told me it is safe for my baby. Should I take Inderal or not? I wonder if other non-drug options exist. Would massage or a chiropractor be safe and helpful?

I want to do what is best for my baby, but at the same time I realize I have 25 weeks of pregnancy to go and I am already exhausted and drained from the past 15 weeks of pain. I am honestly not sure I can take it.

A.The description of your headaches certainly sounds like they are migraine. Such frequent headaches cause the nerves, muscles, vessels and scalp of the head to become sensitized and that is why the scalp is tender.

I agree that Inderal is relatively safe in pregnancy. It has been around a long time and I am not aware of any reported effects on the fetus. You should avoid the calcium channel blockers and the anti-epileptic drugs that are often used for migraine.

The trigger point injections that are planned are safe and may help. Learning biofeedback and other relaxation techniques may also help. If you have a lot of neck and shoulder tightness, massage and/or physical therapy might also help and would be very safe.

Robert Kunkel, MD
Cleveland Clinic Foundation
Cleveland, OH

Do Headache Medications Affect Fertility?
Q. My daughter has migraine headaches and takes Imitrex(R). She and her husband plan to start a family soon and I’m concerned that over-the-counter pain (OTC) medications or Imitrex might impair fertility. Do they?

A. Neither Imitrex nor OTC pain medications impair fertility. However, Imitrex should not be used during pregnancy. Different OTC pain medications have different restrictions for use during pregnancy and your daughter should consult her obstetrician or headache specialist about their use once pregnant.

Stewart J. Tepper, MD
Cleveland Clinic Foundation
Cleveland, OH

Doubts about Feverfew
Q. I’ve read about a product of a standardized dose of feverfew combined with vitamin B-12 and magnesium. Is this product still on the market? Do you know of products of standardized doses of feverfew?

A. The combination product of Vitamin B2, magnesium and feverfew is called Migralief(R), and the dose is two tablets per day. The recommended supplement for migraine is actually Vitamin B2, which is riboflavin, and not Vitamin B12.

The evidence for the effectiveness or safety of feverfew is actually very poor, and I no longer recommend it for my patients. Recent placebo controlled studies on the purified derivative of feverfew have been negative and there are safety concerns regarding a post-feverfew withdrawal syndrome involving muscle aches. So I would not take feverfew in any form, as I don’t think it works and may not be safe.

The dose for Vitamin B2 for migraine prevention has not been established. One study suggests that a dose as low as 25 mg may be active; another study suggests a 400 mg dose. Because the dose is not clear, I usually tell my patients to take 100-200 mg/day.

The dose for magnesium migraine prevention is 400-600 mg/day of chelated magnesium, available as magnesium oxide, magnesium taurate, magnesium glycinate, and sometimes just as chelated magnesium. The limiting side effect can be diarrhea.

Stewart J. Tepper, MD
Cleveland Clinic Foundation
Cleveland, OH

Vitamins Have Side Effects, Too
Q. I read on your Web site that some vitamins can cause headaches. I have been off vitamins now for three weeks and feel much better.

If I wanted to take a multivitamin supplement without niacin or excessive amounts of vitamin A, what do you recommend?

A. You are raising an important issue—vitamins, like every drug, have potential side effects. One should never assume that just because an agent is ”natural,” it is entirely safe. High doses of vitamin A and niacin, in particular, can be associated with headache. Sometimes, agents that are used to manufacture the vitamin tablet, like some of the sweetening agents and dyes, can cause headaches in susceptible individuals. You can discuss this with your pharmacist, who can suggest another product, but you should also consider whether you need to take multi-vitamins at all.

Mark Green, MD
Columbia-Presbyterian
Headache Center
New York, NY

Recommendations for Migraine Preventives
Q. I suffer from migraines and was taking Depakote(R) as a migraine preventive for several years until it eventually didn’t work as well. I am now on Topamax(R), but as I increased the dose it upset my stomach. I still have a bit of an upset stomach, though it seems to be improving. My doctor has suggested that I try Keppra(R) if it doesn’t improve. However, my blood pressure tends to lean toward low and I’ve read that Keppra can lower blood pressure. My other concern is that I heard it wasn’t FDA approved.

Can you tell me what you know about this drug? What other preventive drugs are available?

A. Gastrointestinal upset in some form is not highly unusual with Topamax. When it comes to adverse events, there are several things about dosing Topamax that are important to recognize. First, the dose that has been studied and shown to have the best combination of efficacy as well as tolerability is a total of 50 mg twice a day. In some cases even taking 100 mg at bedtime can be effective and may improve tolerability. Next, once you attain a stable dose of Topamax, the likelihood is that any side effects you may experience will fade out fairly quickly, usually within a month or two. You can take the medication with food. It does not appreciably alter the absorption of the medication from the intestines.
Keppra is also in the family of medications originally used to treat seizures. Clinical studies of Keppra as a migraine preventive have not shown the same level or consistency of effect as either Depakote or Topamax. Both of these medications have multiple trials demonstrating efficacy and good tolerability. None of the other antiseizure class medications measure up in that regard. While change in blood pressure may be reported as a side effect of Keppra, it is not one that is commonly seen (I never have).
There are five medications that have the best combination of effectiveness and tolerability and should be considered as first-line preventive medications. These are the beta blockers propranolol and timolol, the two antiseizure medications previously mentionedÅ|divalproex sodium (Depakote) and topiramate (Topamax)Å|and the oldest of the migraine preventive medications, amitryptiline.

Frederick Freitag, DO
Diamond Headache Clinic
Chicago, IL

Head Pain Is Gone, but Aura Lingers On
Q. I was first diagnosed with migraine in 1980. The attacks were typical and for the last 10 years I had only a handful of them. Recently, however, there has been a change. I am experiencing frequent aura but the severe pain is mostly gone. I only feel a slight heaviness in my head. Is it something that I should be worried about?

A. It is common for the headache part of migraine to improve or disappear with aging even if the aura symptoms do not. Actually, it is common for the elderly to have auras without headache, often for the first time, and be shocked when they are diagnosed as having migraine.

Mark Green, MD
Columbia-Presbyterian
Headache Center
New York, NY

Dizziness Is Primary Symptom
Q. I suffered for years with migraines with aura, but that stopped after menopause. Now the migraines have returned, but vertigo is my main symptom (along with sensitivity to light/sounds and nausea). I have been diagnosed with basilar migraine.

Can you tell me any effective prescription medication for basilar migraines? Most medications to treat vascular migraines have dizziness as side effects.

A. Dizziness and related symptoms are common in migraine. True vertigo tends to occur as an aura in basilar migraine but not as part of the headache phase in this form of migraine. Basilar migraine also tends to occur in teenagers, not in older adults.

The development of new neurologic symptoms associated with migraine, especially in the middle years of life or later, requires careful evaluation to ensure that something more serious is not mimicking migraine. After you have had a comprehensive examination and appropriate diagnostic tests that reaffirm that this is basilar migraine, then a variety of treatments might be possible. These include the use of nitroglycerin or sublingual nifedipine to attempt to eliminate the aura, and triptans to treat the acute migraine attack.

Frederick Freitag, DO
Diamond Headache Clinic
Chicago, IL

What’s in a CT Scan
Q. My son is suffering from vascular headaches and he has been referred for a CT scan.
What are they looking for?

A. CT scans are performed to make certain an individual’s headaches are not due to a structural abnormality within the head, such as a tumor or other mass. In the most common headaches, like migraine, no abnormalities are seen. MRI scans are also sometimes done in those with migraine to exclude causes of headache that involve the structure of the head, but again, migraine is not associated with significant abnormalities on these scans.
The term ”vascular headaches” is no longer used and I suspect the doctor is referring to migraine.

Mark Green, MD
Columbia-Presbyterian
Headache Center
New York, NY

Treating Paroxysmal Hemicrania
Q. I was diagnosed with paroxysmal hemicrania and was prescribed a medication that is usually used for epilepsy. I tried a weaker anti-inflammatory, but it didn’t work while the new drug does seem to be working. Have you ever heard of someone taking an antiepileptic for paroxysmal hemicrania? Can you give me any other information on the condition?

A. Paroxysmal hemicrania is a rare condition of one-sided head pain that lasts 5 to 45 minutes and may recur several times a day. It occurs more often in women and is accompanied by tearing and redness of the affected eye as well as nasal congestion on the affected side. It is shorter in duration than a cluster attack, but shares similar symptoms. The cause is unknown and scans are usually normal, but there have been a few cases of reported paroxysmal hemicrania due to an abnormality in the brain, so imaging is essential to rule out any underlying cause.

Indomethacin, an anti-inflammatory drug, is the most effective medication for paroxysmal hemicrania, though some of the antiepileptic drugs have also been reported to be beneficial for this condition.

Robert Kunkel, MD
Cleveland Clinic Foundation
Cleveland, OH