Monday, December 2, 2013

Women, ACS, and "atypical" symptoms - new study

I was excited to read the new study "Sex-Specific Chest Pain Characteristics in the Early Diagnosis of Acute Myocardial Infarction." My excitement was tempered when I saw Ryan Radecki's take on the article, however.  

"Fundamentally flawed" - ouch.

True, the study by Gimenez et al. cannot prove, because of study design, that men and women have similar rates of atypical symptoms of ACS. However, I’m not sure that this makes the study fundamentally flawed, let alone “comical.” It’s too easy to criticize a study for not being a highly-powered, well-controlled (yet externally valid!) “gold-standard” investigation. But how do we proceed until that rare trial is conducted? In the meantime, why not analyze this study on its own terms? 

Most importantly, this was a prospective study of undifferentiated chest symptoms. Too much of the literature that is cited on this topic uses registry data, or only enrolls patients with confirmed ACS, or interviews subjects long after the onset of symptoms. While the study by Gimenez et al. may not be perfect, its methods are far more robust than most other literature in this area. Importantly, the results triangulate well with other kinds of evidence out there.

1. In most diseases, women have the same symptoms as men. 

How many other diseases are said to show a gender-based difference in presentation? Not many, it seems - I’m pressed to come up with another example where the literature even suggests a significantly different symptom complex.

Indeed, many studies point to the absence of differences in various condition. For example, men and women with pulmonary embolism seem to have similar rates of various symptoms. Interesting, since PE often produces the same sort of vague, poorly localized symptoms as ACS. Along the same vein, at least one study suggests that pancreatitis presents much the same in women as in men

Well, instead of symptom differences in heart attacks, how about “brain attacks?” Again, it seems that there are few clinically significant differences in the way men and women describe their stroke symptoms.

Even in appendicitis, a condition that manifests in protean ways, and involves anatomy that sits right next to gender-defining organs in the pelvis, it seems that women have pretty much the same symptoms as men!

So, if there are few (no?) other conditions in which men and women are understood to have clinically significant discrepancies in their symptoms, why should we believe that heart disease should be the rare (sole?) exception?

2. Evidence from the cath lab suggest men and women have similar symptoms. 
Balloon occlusion during PCI is, essentially, a temporary MI. The lumen is occluded for however long it takes to open the artery and deploy the stent, and people can have significant ischemic symptoms during this period. This makes for a great study setting - although we aren’t studying symptoms associated with ACS sensu strictu, we are able to prospectively survey the patients about their symptoms not only after artery occlusion, but before and during as well.

A team in Japan did just that, and found that men and women had chest pain-free occlusions at about the same rate, 35%. Another study, in Canada, also found no difference between men and women in the cath lab.

3. Many studies in this area are not designed to address the crucial question. 
Most of the data looking at men’s and women’s symptoms in ACS come from studies that enrolled patients with confirmed ACS. For example, in the Gimenez et al study, they cite a number of studies that suggest that women present with atypical symptoms more often. Unfortunately, Goldberg 1998, Goldberg 2000, and Dey 2009 all examined only patients with diagnosed ACS. As such, they can answer the question “In patients with an existing diagnosis of ACS, do women and men have different symptoms?” They cannot speak to how to approach the patient with undifferentiated chest pain. 

For example, many of these retrospective studies find that women describe back pain somewhat more often than men. But, what if women without ACS also describe back pain more often than men? If this were the case, back pain would not really be useful as an “atypical” symptom. 

It's worth pointing out that one of the few prospective studies, looking specifically for atypical symptoms in men and women, found that women presented typically more often than men!

Wrapping up...
So, while this study may not be the last word on the subject, it provides yet another high-quality element of evidence pointing towards the same conclusion: Both men and women - old and young, diabetic and not - can have typical or atypical symptoms of ACS.


  1. I'm such a sucker for, "women and diabetics present differently!" I wonder if I spend a little extra time hunting down that subtle ACS in a female or diabetic and am missing something in a less than run of the mill male.

  2. If I had a nickel for every time the cardiologist and I both shook our heads and said "Boy, you never can tell..."

  3. As a female heart patient, I'm puzzled by the dismissive tendencies of some docs towards atypical cardiac symptoms - in either men OR women.

    We know that women are underdiagnosed - and then undertreated even when appropriately diagnosed. It's hard enough for women to be taken seriously even when presenting with textbook MI symptoms (as I did - before being misdiagnosed with GERD and sent home from the ER feeling very embarrassed for having made a fuss over "nothing") - never mind convincing women (or men!) to seek immediate medical help even with atypical symptoms.

    Yet researchers continue to dine out on small or flawed or questionable studies, each one claiming to finally put to rest any further debate on men's vs women's symptoms.

    For example, consider the Canadian cath lab study you cite here (McKay 2009)

    After grad student Martha McKay presented her study at the Canadian Cardiovascular Congress that year (to massive media coverage of her so-called "Women's Heart Attack Myth!"), I contacted cardiologist Dr. Sharonne Hayes, founder of the Mayo Women’s Heart Clinic in Rochester, Minnesota, for her take on Martha's study. Here's what she told me:

    “This (cath lab) study demonstrates that men and women experience similar symptoms when they have ischemia due to an acutely occluded coronary artery (which is what happens during MI in many but not all people).

    “What it does NOT translate to is that there are no sex differences in heart attack symptoms. Not every heart attack occurs as a result of sudden, complete blockage such as this.”

    I agree with Ryan Radecki's perspective on the JAMA Intern Med paper, which was yet another study looking only at chest pain. And if you're still convinced that there are "no gender-based differences" in presentation of either cardiac or non-cardiac disease, please take a look at cardiologist Dr. Nieca Goldberg's book 'Women Are Not Small Men' for ample evidence to the contrary.

    1. PS I didn't mean to say that ALL women are "underdiagnosed and then undertreated". There are of course many women who are correctly diagnosed and appropriately treated for cardiac conditions. I meant to add "compared to our male counterparts" after that line. My apologies.

  4. Thanks for commenting Carolyn!

    I think we're 100% in agreement on the most important matter - identifying ACS in everyone, both men & women.

    First off, I think the whole of the evidence (the cath studies, retrospective, and prospective trails) point to the conclusion that the AVERAGE male and the AVERAGE female may have small differences in symptoms (may!), but that these differences are far smaller than the variation in symptoms you see within ALL women or ALL men. That is to say, the within-gender variation in symptoms is far broader that the between-gender variation.

    With that in mind, I don't think that it's clinically useful to teach things like "women typically present atypically." Since everyone can present atypically, we have to be on guard with every patient.

    An example: Say a patient denies chest pain, but has an odd neck and back pain. How should my test-ordering be different for a man versus a women with these symptoms?

    As for the cath lab studies, I agree that these are not "true" MIs. Perhaps my language was a little, uh, arcane, so it wasn't clear ("ACS sensu strictu"). Nonetheless, while these studies can't be definitive, they add to the rest of the evidence out there.

    I haven't had the pleasure of reading Dr Goldberg's book, but I think the available evidence doesn't suggest that we have to view men & women differently in terms of the questions we ask, or the value of different symptoms. I'd be happy to talk about this more - it's a fascinating intersection between medicine and culture. Great to have you as a reader!

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