Do Women Suffer ‘Broken Heart Syndrome’?

Sex-Specific Differences Observed in Symptoms and Effective Treatments of Cardiovascular Diseases

It’s inspiring to see State Street adorned with American Heart Association flags in celebration of American Heart Month. For a cardiologist, every month should be heart health month, but it does help our cause to intensify the message once a year.

February is also the month when we celebrate the Go Red for Women campaign, a remarkably successful cause campaign launched in 2003 aiming to raise awareness about cardiovascular diseases in women. I remember when I was first captivated by the emerging story surrounding women and cardiovascular diseases. It was at the turn of this century, and there was no denying the data. It had been the most common cause of mortality in the United States for more than 50 years, but it wasn’t till two decades ago that we noted a disturbing trend — one that could no longer be ignored.

Each year, the American Heart Association updates heart disease and stroke statistics in the United States. It is a comprehensive and exhaustive evaluation of the impact of cardiovascular diseases on the U.S. population as a whole.  The document is rich with data on everything from mortality trends to survey results regarding all the known risk factors that drive these diseases. It breaks down data by type — six different diagnoses make up cardiovascular diseases, of which coronary heart disease and stroke are the two most prevalent — sex, age, and race.

The figure I remember most vividly was one that compared the disease-related mortality in men and women over time. Starting in 1979, with the help of research improving our understanding of these diseases and development of advances in drug therapy and mechanical treatment of coronary heart disease, men derived a drastic and steep decline in mortality. The trend was good reason to celebrate.

In complete contrast, the mortality trend among women was climbing; it reached its peak in 2000. The mortality gap in cardiovascular diseases between men and women was widening and caught us, the medical community, completely off guard. We would spend the next two decades first deconstructing the possible explanations for this trend and then using the power of science, education, and social media, among other things, to construct solutions.

The Campaign

The Go Red for Women campaign became the microphone through which we would spend the next two decades disseminating the message about the under-recognized risks of cardiovascular diseases in women. In addition to spreading the word about the risk, the campaign has had immense impact through various other avenues.

Advocacy efforts led to passage of the congressional Heart Disease Education, Analysis, Research, and Treatment (HEART) for Women Act in 2011 mandating that there be adequate representation of women and racial and ethnic minorities in clinical studies, that studies be powered to examine sex-specific outcomes, and that quality and access of care for women with such diseases be reported.

This act was much needed given that majority of groundbreaking trials, which led to approval of many of the lifesaving treatments, extrapolates data from predominantly white male cohorts to apply to females and minorities. What has become clear is that women are not small white men and that sex-based differences do play a role in determining the impact of treatments.

Improving representation of women in trials is now a mandate by the FDA. This directive has and should continue to help us better understand sex-specific differences in the treatment of cardiovascular diseases. Thanks to the campaign, messaging remains strong, now existing in over 50 countries, and continues to help to shape the cause.

The Differences

Over the last two decades, we have uncovered many striking differences in the diseases that are specific to women. First, it didn’t take a deep dive to realize that part of the explanation for the worrisome mortality trends was related to perception. Women did not perceive themselves at risk for cardiovascular diseases, and furthermore, providers did not think women were at risk for cardiovascular diseases, in particular heart disease. Women who were at risk were unaware. Even when they had more pressing symptoms, they were more likely to present late in the course of what often was a heart attack.

Second, there was concern that women did not have classic symptoms of what is infamously known as the “Hollywood heart attack” — a man clutching his chest and falling to the ground. Thanks to detailed study on sex differences in symptoms, we now know that women are more likely to have atypical symptoms, but the vast majority actually do have more classic symptoms at the time of their heart attack. Women need to pay attention to symptoms that are not usual for them and occur with exertion or stress.

Third, we have discovered that women are not only at risk for what is considered a traditional heart attack where there is atherosclerosis resulting in visible narrowing of the heart arteries. They are also having heart attacks with open arteries. Women can have chest pain symptoms with testing suggesting impaired blood flow to the heart muscle without narrowing of the main heart arteries. These two entities, “myocardial infarction with open arteries” and “microvascular angina,” are almost always seen in women. The observation has led to the hypothesis that there are sex differences in how atherosclerosis effects blood vessels — women may be more likely to have diffuse disease of the major heart arteries and are more likely to have problems with the small microvessels. This becomes important when considering treatment options, as medical and lifestyle therapy plays a larger role in treating these entities.

In addition, we have uncovered two fascinating diagnoses that are not new but have been underappreciated until recently. Both are almost exclusively seen in women. First, the “Broken Heart Syndrome” (also known as Takotsubo Syndrome) has been described now in thousands of cases. It is a heart attack usually triggered by an emotional event. The usual presentation is a woman presenting with classic signs and symptoms of a heart attack after experiencing something emotional and or tragic. The heart arteries have no blockages but the heart muscle appears to be stunned. Most patients are treated supportively and make a full recovery.

The other is known as Spontaneous Coronary Artery Dissection or SCAD. SCAD occurs in younger women and presents like a heart attack. When the heart arteries are evaluated, there appears to be a spontaneous tear of one of the heart arteries. Though the exact cause of SCAD is not confirmed, we have learned through large patient registries that conservative treatment is preferred over mechanical treatment and safest.

Lastly, as the treatment armamentarium — or medicines, equipment, and techniques — has expanded for women presenting with a heart attacks, we started to notice sex-specific risks of treatments. For example, women undergoing invasive treatments such as heart catheterizations and stent placement were noted to have increased risk of procedural bleeding and with it were having worse outcomes. This sex-specific risk is thought to be multifactorial and possibly related to anatomical differences in arteries and in the effects of blood thinners and their metabolism in women. In an attempt to mitigate the bleeding risk, current practice has evolved away from using drugs that are associated with increased bleeding. Most importantly, we have transitioned to using the smaller, safer artery in the wrist (radial artery) as the default site for procedural access. This has had enormous impact on bleeding complications and has preferentially improved outcomes among women given their predisposition.

These are just a few of the many lessons we have learned trying to navigate our way to answers about women and cardiovascular diseases in the 21st century. With 20/20 hindsight in the year 2020, it is remarkable to see where we were and how far we have come in two decades. The colossal team effort speaks to the power of science, community, advocacy, and unwavering commitment to ensure that we study and treat all at risk for cardiovascular diseases, especially women and minorities. Though much more work is needed, there is no doubt that our heart is in the right place when it comes to women and these diseases.

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