“We see migraine as black and white: You either have it or you don’t. If you had it before but you don’t have it now, are you then back in the pool of patients who never had migraine and never will? Or should this be considered a separate pool that we should also look at? Right now, we are not looking at people who have had migraine and now do not have it, and to fully understand the relationship between migraine and cardiovascular disease, we need to be more sophisticated in how we collect information on migraine.” – Tobias Kurth
Tobias Kurth, MD, ScD, is a professor of public health and epidemiology at the Institute of Public Health at Charité – Universitätsmedizin Berlin, Germany, and an adjunct professor of epidemiology at the Harvard T.H. Chan School of Public Health, Boston, US.
His research focuses on the relationship between neurological and cardiovascular disease, particularly emphasizing the association between migraine and the risk of stroke and myocardial infarction. He recently co-authored a Clinical Outlook article in Nature Reviews Cardiology highlighting the challenges involved with understanding this association and is calling for continued research to guide future risk assessment and treatment.
In this Migraine Science Collaborative interview, Kurth spoke with freelance writer Kayt Sukel about why we still don’t know what is behind the association, the need for better classification of migraine to understand the link, and much more. The interview has been edited for clarity and length.
What first piqued your interest in studying the connection between migraine and cardiovascular disease?
Cardiovascular diseases are major chronic conditions, and they are quite common at the population level. If you have a factor, like migraine, that may be linked to those diseases, it’s of obvious importance to understand the link. Migraine itself is also very common. But there is a lot of uncertainty about what might explain the association.
Scientists have known about this association for decades. Why don’t we have a better understanding of the mechanisms that connect migraine and cardiovascular disease?
That’s the key question. Yes, we see this link, but the question we need to answer is why. There are several mechanisms that could explain this. Or it could be a factor that is not causally related to migraine.
Scientists are looking at many different things that may connect migraine to the vascular system. But so far, we haven’t identified a clear mechanism. There are many thoughts about biomarkers, inflammatory markers, genetic markers, vascular function – this and that. But the big issue, from my perspective, is that we are not really looking at migraine as many patients experience it.
Often, we categorize a person as having migraine during a one-time assessment and then project that they will continue to have it in the future. But migraine, of course, can change across the lifespan, and we are not currently considering that in terms of measuring migraine or how we analyze its relationship with cardiovascular health.
We see migraine as black and white: You either have it or you don’t. If you had it before but you don’t have it now, are you then back in the pool of patients who never had migraine and never will? Or should this be considered a separate pool that we should also look at? Right now, we are not looking at people who have had migraine and now do not have it, and to fully understand the relationship between migraine and cardiovascular disease, we need to be more sophisticated in how we collect information on migraine.
What we need to understand is whether people have migraine across a certain time frame – the pattern of migraine attacks that occur. I hope we can get information on people who once had migraine but now their migraine pain has gone away. Currently, large-scale studies do not collect this information.
What work are you doing in this area?
We are currently doing studies where we have proxy information on the time frame and we see a different pattern when it comes to cardiovascular risk. The data suggest that if you have active migraine, your vascular risk score is actually quite low. But it changes when you move from “I have migraine,” to “I no longer have migraine.” There appears to be something happening there that is linked to vascular health, and it’s something we would like to understand, especially since the data we are currently examining suggest that if you have active migraine, you likely have a rather healthy vascular system.
Researchers have studied everything from hormones to inflammation to explain the link between migraine and cardiovascular disease. What do you think about that research?
The results from hormone studies are not consistent. There is some evidence that hormones may play a role, but I am not convinced that’s because more females have migraine. But that, too, may be indicative of biases at play. Far too often, when a woman reports a headache, we classify it as a migraine. When a man has headache, we look for some other cause. I think part of the stark difference we see between males and females may be attributed to biases in collecting information, but, even so, the hormone work hasn’t consistently demonstrated that a higher level of one hormone or a lower level of some other hormone is somehow linked to the association between migraine and cardiovascular disease.
Certainly, the link may be more complex than that; we may be completely missing some other factor that is linked to migraine and cardiovascular disease. But, as I mentioned, we need to first look in more detail at the migraine activity state. Is it active migraine? Non-active? In the past?
I don’t think the link is related to migraine-specific treatments, or to hormones or genes. We’ve been looking at this link for decades but haven’t figured it out yet. I don’t think we are missing something big; otherwise, it would be very obvious. Moving forward, we should be more open in our thinking about what we may be missing as we try to understand this interaction.
We need to be better in getting data that allow us to measure migraine correctly at the population level and follow people over time. You have to follow people for a long time before they experience a cardiovascular disease event – and it’s likely, if they have a heart attack or stroke, that they don’t have active migraine anymore. When did they stop having migraine? What happened to their vascular system since then? This is just pure speculation, but it’s possible that whatever stopped the migraine is also affecting the vascular system over time, causing an exponential increase in vascular disease.
Might people with active migraine have some kind of protective factor that gives them a healthier vascular profile?
Maybe you need to have a healthy vascular system to actually feel the migraine pain or to have some kind of triggering threshold where the migraine cascade improves circulation. We don’t know. We need to turn all the puzzle pieces face up and try to put them together.
Given that primary care physicians get so little training in migraine, what should they be telling their patients with migraine with regard to reducing their risk of stroke or myocardial infarction? And what should patients do?
First of all, the most important thing is that doctors provide good treatment for acute migraine or some type of preventive medication for people with frequent migraine. That said, over the long run, if you are a primary care physician and are seeing a patient for many years, it’s important to understand the pattern of their migraine across the life course. If you see something is changing – perhaps the pain goes away or something else changes – it might make sense to check the cardiovascular health status of the patient, which the doctor should be doing anyway. I think it is also important, given the stroke link, that doctors educate patients about stroke symptoms, how they differ from their migraine aura symptoms and tell them that, if they experience those symptoms, they should go to the hospital immediately.
As for what patients with migraine should do to reduce the risk of cardiovascular disease, to the best of my knowledge there’s nothing they should be doing differently than anyone else. Live a healthy lifestyle, eat healthy foods, and exercise regularly. This is a no-brainer.
Right now, we treat migraine as a predictor for cardiovascular disease. What does that mean for the migraine patient, above and beyond making the lifestyle changes that we know can help lessen the impact of major drivers of cardiovascular disease like hypertension? Should the migraine patient be treated differently? Because we know that not everyone with migraine will get cardiovascular disease. We need to understand who does, and then be able to communicate what they can do to lessen their risk of dying from stroke or myocardial infarction.
You work at the population health level. How can epidemiological researchers like you work best with basic scientists and clinical researchers to solve this puzzle?
My collaborations with basic scientists are very fruitful, as they see things in a very similar way. They use a different framework or different methods, but they share a fundamental understanding of the questions we should be asking and how to answer them.
Ideally, when we can address this problem from different perspectives, applying different tools and methods to the right data, we can get the answers we are looking for. I appreciate all the work I do with pharmacologists, basic science researchers, epidemiologists, and clinicians. All of us working together is important to address this very big question; the more we discuss the issue, the better we can come up with ways to address it. And, frankly, science only happens when you disagree because then you must provide evidence to support your views. When we disagree, we can detect where things are missing and try to find ways to fill in the blanks as we move forward.
Kayt Sukel is a freelance writer based outside of Houston, Texas.
Image credit: altitudevisual/123RF Stock Photo.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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