Cardiac research and the mystery of the missing facts

by Carolyn Thomas    @HeartSisters

Over the years, I’ve had to teach myself the bare bone basics of interpreting cardiac studies. I’m certainly no research scientist (although I did spend 20 years of my life with one – does that count at all?) but I can tell you that one good place I like to start is the methodology section of any study.

Wait!  Don’t leave yet!   I know, I know, this may seem crushingly dull. But the methods info is how I learned, for example, that out of over 5,000 participants recruited for the $100 million ISCHEMIA study in 2019, only 23 per cent were women. At the time, I offered a helpful editing suggestion to the Washington Post about their sensational coverage of ISCHEMIA (“Stents and Bypass Surgery are No More Effective Than Drugs!!” ) by requesting this important clarifier added to the end of that headline: FOR MEN!”       .        .    

The reality is that you simply cannot offer up credible scientific conclusions about how research results will affect women’s health care when you are deliberately under-representing over half the population in your study.

And yet this gender gap keeps happening – especially in heart research.

Despite growing awareness (and even funding requirements) that women must be represented equitably across all areas of medical research, we still see that women’s participation “has been the lowest in cardiovascular trials”, as McGill University researchers Drs. Louise Pilote and Valeria Raparelli wrote in 2018.

I often feel the urge to offer my own helpful clarifiers about many studies out there after reading their methodology sections. These typically include information about:

  • the participants (most researchers now prefer that word over the previously used “subjects”) such as age, race, gender, and the number of participants
  • the materials used by researchers to gather and analyze data from the study (plus a list of sources used and why these sources were essential for this study)
  • the procedures used (such as collection of data or the instructions given to participants)

Consider, for example, a study with a small number of participants. Ten people is considered the reasonably minimal number. But honestly, can a group of ten people really call itself a scientific study? Ten people is not a study – it’s a (pre-COVID) family birthday dinner at my house, which similarly has no business posing as research. The health journalism watchdog Health News Review shares this warning about small medical studies:

“Be vigilant when writing about them, and skeptical when reading about them.”

I feel a similar urge to offer helpful edits when reading about animal  or cell studies in the research laboratory (with an apologetic nod to my friends working in these labs). Whenever I see flashy headlines announcing yet another miracle medical breakthrough, but based only on furry subjects living in little metal cages, I try to correct this intentional obfuscation with a disclaimer, like:

“GOOD NEWS IF YOU’RE A MOUSE!”

Call me when you move into human trials.

There are a number of specific issues surrounding the experiences of laboratory animals vs. humans, but none are more frightening than this: animal models are poor predictors of treatment safety in humans. 

A review of 221 animal experiments, for example, found agreement in later human studies only 50% of the time, which means it’s essentially random.You could flip a coin with equal predictive accuracy.

Thalidomide was one of the most dramatic examples of this problem during my lifetime – a drug approved in Canada and other countries in the 1950s to treat morning sickness in pregnant women. Thalidomide didn’t cause limb deformity birth defects in baby animals in the lab, but those deformities did happen to over 10,000 babies of pregnant humans.

And don’t even get me started on the wholesale hyping of unpublished, non-peer reviewed medical study results, often distributed in a flood of press releases created by Communications Department staff, only to be picked up verbatim by understaffed and overworked media newsrooms. The trouble with most press releases is the tendency toward over-hyped benefits coupled with under-reporting of potential problems. Again, check out Health News Review for the dangers of questionable science delivered by press release. 

In a study published in the British Medical Journal (BMJ), we learned that exaggerated reporting of medical studies can be traced back to the press releases submitted by 20 leading U.K. universities where the study authors work. Forty per cent of the press releases they investigated included health advice that was not actually found in the original paper. And 36 per cent over-inflated the relevance of animal or cell studies to humans.

Here’s a cardiac study (submitted to, accepted by and published in a real cardiology journal) that I like to mention, mostly because I was so intrigued by its findings a few years ago. It was reported by senior researchers at Harvard and Massachusetts General Hospital in Boston, who called it the Gratitude Research in Acute Coronary Events (GRACE) study.2

Acute Coronary Syndrome (ACS) is a term used to describe any dangerous drop in blood flow feeding the heart muscle. If you’ve been diagnosed with a heart attack, it’s likely that the first potential diagnosis entered into your medical chart in the Emergency Department was ACS. Cardiac symptoms are assumed to be ACS until proven otherwise.

The Boston team knew that within the first year post-ACS diagnosis, about 20 per cent of ACS patients will either be re-admitted to the hospital for cardiac emergencies – or they’ll be dead

They also knew from previous studies that positive psychological well-being is associated with reduced patient mortality.3    So they decided to focus on positive factors like optimism and gratitude for their GRACE study.

Here’s what the Boston researchers learned: the trait of optimism was independently associated with greater physical activity and reduced rates of cardiac re-admissions to the hospital after six months of follow-up. Gratitude was not associated with improved outcomes.

I was about to write a blog post about the GRACE study findings at the time,  but a couple of niggling limitations of this study were bothering me. For example, the researchers followed participants for only six months, despite current stats that suggest the first year is the time period we worry about.

Why weren’t the participants followed up for at least 12 months to address this limitation?  Astonishingly, this disconnect between medical interventions approved for longterm use in chronic illness and the short-term studies their approvals were based on are common (e.g. the Swedish drug study in which “longterm” meant just one year of follow-up).  See also: Our Cardiac Meds – in Real Life, Not Just in Studies

The most glaring limitation, however, was that 84 per cent of the GRACE study participants were white males. The researchers admitted that “the lack of significant differences in outcomes by sex and race may have been due to the relatively small number of women and non-White participants.”

Duh. . .

They further explained that, by the middle of study recruitment, they had even considered limiting the enrollment of white men, but decided that “having a greater number of total participants was the greatest priority.” 

Oh. Well then, okay. . .  

Does this excuse simply let researchers off the hook when they continue to submit papers for publication based on lopsided participant populations in which women and/or racial minorities are deliberately unrepresented?

I understand the pressure on medical researchers to “publish or perish”.  I really do. And I have long suspected that this relentless stress might help to explain why all the really good research topics have already been taken.

As my irreverent Mayo Clinic heart sister Laura Haywood-Cory (who survived a heart attack at age 40 caused by Spontaneous Coronary Artery Dissection) once asked in response to a 2011 Heart Sisters post:

“We really don’t need yet another study that basically comes down to: Sucks to be female. Better luck next life!’, do we?”

Well, Laura – apparently we do.  Because those studies just keep on coming.  

Like most published medical research, the GRACE study includes the standard CYA clause at the end: “future studies are required.”  Maybe those future studies will include an accurate acknowledgement of the difference between longterm and short term, and more attention to recruiting an adequately representative gender/racial balance.

But it’s not just me expecting this improvement. For all researchers counting on National Institutes of Health funding, it’s the law now, as the NIH/U.S. Department of Health and Human Services website warns:

“All NIH-funded clinical research must address plans for the inclusion of women and minorities within the application or proposal. The primary goal of this law is to ensure that research findings can be generalizable to the entire population.”

The entire population. Is it too much to expect that women and minorities must be considered part of the “entire population”?  

While you’re pondering that trick question, consider educating yourself.  Check out Health News Review’s excellent user-friendly toolkit called Tips for Analyzing Studies, Medical Evidence and Health Care Claims.

And until you do that, please don’t forward to your friends the latest medical miracle breakthrough that’s just been “published” on Facebook – because the fact is that it’s likely neither a miracle, nor a breakthrough.

1. P. Perel, I. Roberts, E. Sena, et al. “Comparison of treatment effects between animal experiments and clinical trials: systematic review.” BMJ, 334 (2007), pp. 197-203
2. Huffman JC, Beale EE, Celano CM, et al. “Effects of Optimism and Gratitude on Physical Activity, Biomarkers, and Readmissions After an Acute Coronary Syndrome: The Gratitude Research in Acute Coronary Events Study.” Circ Cardiovasc Qual Outcomes. 2016;9(1):55-63.
3. Chida Y, Steptoe A. “Positive psychological well-being and mortality: a quantitative review of prospective observational studies.” Psychosom Med. 2008 Sep; 70(7):741-56.
Image: Enrique Meseguer, Pixabay

Q:  What would you like to see future medical research focus on?

.

NOTE FROM CAROLYN:  I wrote more about what to look for in cardiac research in my book, A Woman’s Guide to Living with Heart Disease , published by Johns Hopkins University Press.  You can ask for it at your local library or favourite bookshop, or order it online (paperback, hardcover or e-book) at Amazon, or order it directly from my publisher (use their code HTWN to save 20% off the list price of my book).

See also:

– Educate yourself! Health News Review’s excellent user-friendly toolkit called Tips for Analyzing Studies, Medical Evidence and Health Care Claims

Understanding Clinical Trials: A Jargon Busting Guide –  a useful non-scientist’s glossary of medical research terminology from Marie Ennis- O’Connor

Is it enough to have “enough” women in cardiac studies?

Our Cardiac Meds – in Real Life, Not Just in Studies

Are women being left behind in cardiac research?

The ‘bikini approach’ to women’s health research

Cardiac research: where did all the women go?

12 thoughts on “Cardiac research and the mystery of the missing facts

  1. Another post that casts light in an insufficiently understood truth. This demonstrates not only the need for much broader participation in studies, but designing the study so that data will reveal significant differences in outcomes.

    Larger numbers of women, of broader ethnic and social groupings, is good, but much more useful if data is not homogenized soup.

    As you have demonstrated so well, little scientific research has been done on women’s bodies, and, when done well, often points to departures from the status quo. This adds urgency to a current discussion that advocates replacement of biological sex in medical records with self-identification.

    Better understanding of biological reality is a matter of life and death, and particularly for women.

    Liked by 1 person

    1. Hi Kathleen – thanks for raising such an important point!! A common criticism of previous cardiac research is that results were NOT always analyzed in sex-specific ways. That meant the essentially useless homogenized soup you mention.

      As Dr. Thais Coutinho, a female cardiologist and researcher at the University of Ottawa Heart Institute said in a very interesting CBC interview in 2019: “2/3 of the clinical cardiovascular research ever done has either excluded women or if it did include them, did not or could not analyze them separately. As a result there is no way to know if the findings of those studies apply as much to women as men.”

      You’re so right – better understanding of biological reality is a matter of life and death for women. Well said!

      Take care, stay safe. . . ♥

      Like

  2. I would like to see some heart focused studies that are exclusively about women. Taking previous male-dominated studies and replicating them with women.

    The ISCHEMIA study was particularly disturbing to me … having a stent placed right around the same time the research was published.

    I asked my cardiologist if that meant I could have just skipped the stent and went on my merry way? He smiled and shook his head. He is a firm believer in knowing the newest research that is out there but making individual decisions based on his knowledge of his patients. The Interventional cardiologist discussed the research and my case and he said that because of my diabetes and inability to take statins, I was just too high a risk to not put in a stent.

    Research is important to move any field of science forward but it will never substitute for an astute intuitive clinician weighing all the nuances of an individual case.

    I never asked my cardiologist if he considered my sex in making the decision…. I’ll have to ask him at my check up next month!

    Liked by 1 person

    1. Hello Jill – I think you’re 100% correct in choosing to trust the expertise of your own physician. This makes sense, and if you do have trustworthy clinicians, that’s a bonus.

      The response on social media to the ISCHEMIA study was not surprising after it was published: generally the interventional cardiologists (the ones who implant stents for a living) and the cardiac surgeons (the ones who do bypass surgery for a living) were more likely to react negatively to the results than the preventive cardiologists (the ones whose first line of defense would be the OMT, “Optimal Medical Treatment” as described in the study – like behaviour modifications and cardiac medications) loved it!

      An even more volatile response was reported by BBC News in the U.K. last year after another study called EXCEL was published, which I described at the time as “dueling heart specialists engaged in a very public pissing contest over how best to treat heart patients diagnosed with blockages in the left main coronary artery.” This time, more conflict-of-interest complications in that EXCEL was funded by the stent manufacturer, Abbott. I wrote more on this in Stents vs. Bypass Surgery vs. Trust“.

      Another reminder to read the fine print about financial conflict-of-interest disclosures (and the Methodology section!) in all clinical trials.

      Take care, stay safe. . . ♥

      Like

  3. Carolyn, I can’t help but ask what your thoughts on COVID vaccines are in light of your information about research tips. I took a quick look at the site —- seems there are many warning signs connected to information about vaccines….. there aren’t to my knowledge any solid long term studies…. and I wonder about the under-reporting of symptoms as well…. A whole different topic than heart issues….. but… my curiosity got the best of me.

    Thanks for your post and the links! I can’t believe that medical studies are in the dark ages…..still – how about not funding studies for white males anymore…. and catching up on the other entire population!!!!

    LisaMarie

    Liked by 1 person

    1. Hello LisaMarie – I can tell you my personal opinion, but with one important disclaimer: I’m NOT a physician so cannot offer any medical advice to individual readers, and my own vaccination decisions cannot be considered as a substitute for medical advice from a trained physician.

      I’m a person living with complex cardiac issues – which means I’m regarded as high risk for catching the corona virus, and at high risk for a very poor outcome if I do.

      So I decided that I simply cannot get sick. I closely follow the public health directives of experts like Dr. Fauci and Dr. Bonnie Henry (our own top doctor here in BC) – both are physicians whose long careers have been devoted to the study of infectious diseases and pandemics (AIDS, Ebola, H1N1, SARS, etc.) I tend to disregard what conspiracy theorists, or political appointees at press conferences, have to say. I think this tendency helps me to cut through the noise.

      At first, I thought that I’d likely wait-and-see until the vaccinations were well underway before I’d decide, because of the competitive hyper-speed of vaccine research, but I’ve been following the progress of those who have been vaccinated so far and feel reassured. In fact, I’m now a bit alarmed by the delay in promised vaccine delivery here in Canada and elsewhere. In answer to your questions, it’s true there’s clearly no longterm data yet on current vaccines. There is so much we don’t know about a virus that behaves so differently than other viruses – the experts are learning as they go, and now we have these variant mutations to think about.

      What I’m increasingly convinced of by now is that the risks of me getting sick with COVID are far worse than a vaccine side effect might be at this point. It goes back to trust: I look to those I regard as trustworthy for their opinions.

      And YES, let’s catch up with the OTHER “entire population” in all of our research!

      Take care, stay safe. . . ♥

      Like

      1. I am very high risk with multiple co-morbidities. I too thought at first I would wait and see. But when my health plan contacted me because I qualified for Vaccination Phase 1B …I signed up immediately without hesitation. I’ve had my first dose of the Moderna Vaccine, I get my second dose in a couple weeks.

        I took care of patients intubated and on ventilators for 2 decades. No one wants to go through that if at all preventable.

        Liked by 1 person

    1. I’d like to see more research on this issue too, Holly! Most heart-related pain research seems to be focused on new-onset chest pain in order to rule out a diagnosis of acute coronary syndrome. The British Medical Journal (BMJ) did an interesting review of such studies in 2017 that concluded: “Our evidence map suggests that while much is known about the differing presentations of obstructive cardiac pain in middle-aged women, little research focused on young and old women, on non-obstructive cardiac pain, or on pain self-management interventions to assist women to manage their cardiac pain.”

      What IS encouraging however is the number of academic hospitals that have established a Women’s Heart Clinic that focuses specifically on women’s cardiac issues – and thus can attract researchers to join their teams. I live in hope!

      Take care, stay safe. . . ♥

      Like

  4. It’s especially fun being a female heart patient in the midst of the pandemic. It’s even more fun when you can’t have the vaccine because of your severe allergies.
    GRRRR!

    Liked by 1 person

    1. That sounds like NO fun at all, Sandra. There’s no good way around those two realities for heart patients with allergies, or with medical exemptions that might make the vaccine impossible, other than the careful public health precautions we’ve been practicing since early 2020.

      Ideally, if enough of us do get vaccinated, that herd immunity we’ve been hearing about will protect people like you.

      Meanwhile, take care and STAY SAFE! ♥

      Like

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