Migraine: A New Cardiovascular Risk Factor?

I’m going to get personal here.  I had my first migraine - in my life - about three weeks ago. For those of you who have been longtime sufferers, I am truly sorry.  I was literally testing my own neck stiffness to make sure I didn’t have meningitis. But aside from the blistering pain knocking you out of commission for several hours (or several days), a new study appearing in the BMJ suggests there is something else migraine sufferers need to worry about – cardiovascular disease.

For the video version of this post, click here.

Researchers used data from the Nurses Health Study 2, a large, questionnaire-based prospective cohort study that began back in 1989 and enrolled over 100,000 nurses. The idea here was that the nurses (all female by the way) would be more reliable when answering health-related questionnaires than the general public.

In 1989, 1993, and 1995 the questionnaire asked if the women had been diagnosed, by a physician, with migraine. That’s it. No information on treatment, severity, or the presence of aura – a factor that has been associated with cardiovascular disease in the past.

This response was linked to subsequent major cardiovascular events including heart attack, stroke, and coronary interventions.

The researchers found a higher rate of this outcome among those who had been diagnosed with migraine. In fact, even after adjusting for risk factors like age, cholesterol, diabetes, hypertension, smoking, and more, the risk was still elevated by about 50%. So those of us with migraines – is it time to freak out?

Not too much.  The overall rate of major cardiovascular events in this cohort was just over 1% - not exactly common. That means the absolute risk increase is 0.5%, which doesn’t sound quite as dramatic as the 50% relative risk increase.  Putting that another way, for every 200 patients in this cohort with migraine, there was one extra case of cardiovascular disease.  Not exactly a risk factor to write home about.

But, to be fair, cardiovascular disease gets more common as we age – had the study had even longer follow-up, we might have seen a higher event rate.

Other studies have found similar findings with migraine. The women’s health study, for instance, found a nearly two-fold increased risk in cardiovascular events, but only in those who had migraine with aura – a covariate missing from the current dataset.

Should women with migraine take precautions against cardiovascular disease? The jury is out. Since we don’t know the mechanism of the link, if any, we don’t know the best way to treat it.  But clearly any studies of migraine therapy would do well to keep an eye on cardiovascular endpoints.

Being a woman versus being womanly: the implications after heart attack

For the video version of this post, click here. There are two elements you can expect to see in almost any study: the first is some effect size - a measure of association between an exposure and outcome. The second is a subgroup analysis - a report of how that effect size differs among different groups. Sex is an extremely common subgroup to analyze - lots of things differ between men and women. But a really unique study appearing in the Journal of the American College of Cardiology suggests that sex might not matter when it comes to coronary disease. What really matters is gender.

The study, with cumbersome acronym GENESIS-PRAXY, examined 273 women and 636 men of age less than 55 who were hospitalized with Acute Coronary Syndrome (ACS). Sex was based on self-report, and was binary (man or woman). But gender isn’t sex. Gender is a social construct that represents self-identity, societal roles, expectations and personality traits, and can be a continuum - think masculine and feminine.

The authors created a questionnaire that attempted to assign a value to gender. Basically, questions like - “how much of the child-rearing do you perform” or “are you the primary breadwinner for your household” - in other words these are based on traditional gender norms - but that’s as good a place to start as any. A score of 100 on the gender scale was “all feminine”, and a score of 0 “all masculine”.  Most of the males in the study clustered on the masculine end of the spectrum, while the females were more diverse across the gender continuum.

What was striking is that the primary outcome - recurrence of acute coronary syndrome within a year, was the same regardless of sex - 3% in men and women.  But a greater degree of “femininity” was significantly associated with a higher recurrence rate. Feminine people (be they male or female) had around a 5% recurrence rate compared to 2% of masculine people. This was true even after adjustment for sex, so we’re not simply looking at sex in a different way - gender is its own beast.

What does it all mean?  Well, it shows us that our binary classification of sex may be too limited in the biomedical field. Of course, there will always be hard and quantifiable physiologic differences between men and women. But what is so cool is that it’s the more difficult to quantify gender-related differences that may matter most when it comes to health and disease.

Of course, this conclusion is way too big to be supported by one small study with a 3% event rate. But given the surprising and really interesting nature of the results, I’m sure we’ll have many more studies of this sort following close behind.