Why didn’t I know, until recently, that cardiovascular disease (CVD) is the number one killer of both women and men in the United States? As the leading cause of death, CVD takes one American life every 33 seconds. Still, most Americans aren’t aware about the extent of the impact of CVD—even though this is far from a new phenomenon! Heart disease has been the leading cause of death in the U.S. since 1921, and yet, over a century later, less than half of the respondents of a 2023 survey could name the nation’s number one killer. Perhaps most shocking is that heart disease causes more deaths in the U.S. than all types of cancer combined!
Women’s heart health remains particularly neglected and understudied. Over 60 million women in the U.S. live with some form of heart disease — that’s almost half of women above the age of 20. But despite the overwhelming need for better care, women remain underdiagnosed and undertreated, leading to worse health outcomes. For many of them, their symptoms don’t fit the traditional understanding of heart disease that was developed primarily through research conducted on men.
According to cardiologist Dr. Lisa Freed, director of Yale New Haven Hospital’s Women’s Heart and Vascular Program, “Women just don’t always get the same care that men get. So they don’t always get the same labs drawn. They don’t always get the same advice. And that’s not every practitioner. But if you look at the literature, you’ll see it’s repetitive: underdiagnosed, underrecognized, undertreated.”
This longstanding discrepancy is nothing new. CVD had historically—and mistakenly—been considered a ‘man’s disease. For example, in the 1960s, the name of an American Heart Association conference in Oregon was “How Can I Help My Husband Cope with Heart Disease?” It should be no surprise, therefore, that misperceptions about CVD have had and continue to have far-reaching implications for women’s health.
Despite the important progress that has been made in the decades in between, why are women still being underdiagnosed and undertreated for CVD when they account for nearly half of all CVD deaths in the United States? How is it that, in comparison to men, women are 50% more likely to be misdiagnosed while having a heart attack—many of them sent home from the emergency room mid-heart attack? And most concerningly, how is it that maternal deaths due to CVD have more than doubled in the U.S. since 1999? These gaps in women’s CVD care require persistent attention.
The Female Heart: Anatomy, Hormones, and Overlooked Risk Factors
Although research has made it increasingly clear that we can’t continue transferring knowledge derived from decades of male-centered research to female patients, blind spots in treating women persist. The female cardiovascular system differs fundamentally from males in ways that medicine has only recently begun to comprehend.
On average, the female heart is 25% smaller than a man’s heart, and even after scaling for body size, the difference in physiology persists. Since women have, on average, a lower cardiac output than men—meaning they pump less blood—women tend to have a higher resting heart rate than men to compensate for this difference. In other words, women’s hearts must beat faster to pump the same amount of blood as men’s hearts.
Women’s hormones also play a significant role in heart health. Estrogen and progesterone are essential for maintaining a healthy heart. Estrogen, for example, is thought to prevent CVD in premenopausal women by relaxing blood vessels and promoting healthy cholesterol levels. Given such protective effects, when hormone levels fluctuate, women become particularly susceptible to developing CVD. This explains why postmenopausal women—whose estrogen and progesterone levels are diminished—face higher risks of developing CVD and related conditions like hypertension, as I explored in my previous blog post about menopause.
Pregnancy remains one of the most critical yet understudied areas within women’s cardiovascular health. A woman’s heart and blood vessels work harder during pregnancy to support fetal development. Often called the ultimate “stress test,” pregnancy puts women at risk for developing various cardiovascular conditions—supposedly offering a glimpse into the future of her cardiovascular health. According to a 2019 study, women who experience heart complications during pregnancy have twice the risk of developing CVD later in life. Alarmingly, these same pregnancy-related cardiovascular complications are contributing to staggering rates of maternal mortality in the U.S., with maternal deaths from such complications more than doubling over the past two decades.
Autoimmune diseases, which disproportionately affect women (as my first article explores), are also a significant and overlooked risk factor for developing CVD. Conditions including lupus and rheumatoid arthritis can trigger inflammation and damage blood vessels, putting individuals at a greater risk for developing heart complications. As Dr. Margaret Furman, Co-Director of the Cardio-Rheumatology Program at Yale New Haven Health, explains, “It is important to make women aware of what their risk factors are that could be unique to them, such as pregnancy, autoimmune diseases, and family history.”
Between differences in anatomy, hormones, and life stages such as pregnancy and menopause, caring for women with CVD demands a fundamental shift in how we approach diagnosis and treatment—especially since women are more likely than men to develop certain rarer forms of CVD.
Coronary Artery Disease: A Textbook Diagnosis
The most common type of CVD for both men and women in the U.S. is coronary artery disease, the leading cause of heart attacks in the U.S. This condition occurs when arteries become clogged with plaque, restricting blood flow to the heart. When blood flow becomes blocked, it results in a myocardial infarction—the medical term for a heart attack.
When we think of a heart attack, we’ve long thought of the “Hollywood heart attack.” A TV character suddenly experiences chest pain; he clutches his chest and falls to the ground. This is, in many cases, overly-dramatic. But one aspect of the stereotype is true: chest pain or pressure is in fact the predominant symptom of a heart attack—regardless of sex.
In recent years, you may have heard that women are more likely to experience other symptoms such as nausea, vomiting, or shortness of breath—symptoms which are not intuitively associated with a heart attack, or may be attributed to anxiety. Over the past two decades, healthcare professionals and public health campaigns have emphasized the importance of recognizing these heart attack symptoms in women.
For example, in 2004, when the American Heart Association launched their campaign Go Red for Women to raise awareness about heart disease in women, a major goal was to raise awareness about these types of symptoms in women. As public interest in women’s cardiovascular heart health grew, media outlets began running headlines like “Same Disease, Different Symptoms,” or “Women: Heart Attacks Can Mimic Flu Symptoms,” spreading important information about the variation in heart attack presentation.
However, according to Dr. Freed, this effort to increase awareness has had unintended consequences; a necessary correction became an overcorrection. She explains, “We promoted the fact that so-called ‘atypical’ symptoms are more common in women—which they are—but that translated in people’s minds that women only experience these symptoms. And so, when women were having chronic chest pain, they would sit home and reflect, ‘Well, that’s not really the kind of symptoms that women have.’ And practitioners would do the same thing. And so that was a huge mistake.”
Considering that around a third of women experiencing a heart attack don’t experience chest pain or discomfort, a balanced approach is essential: while chest pain remains the most common heart attack symptom for both sexes, healthcare providers and women should remain alert to other, less obvious warning signs.
Research By My Peers in the Women’s Health Research at Yale Fellowship
The Under-Researched Heart Disease: Assessing INOCA
Although coronary artery disease (CAD) is the most well-known type of heart disease, recent research has revealed that many women suffer from a different cardiovascular condition altogether. INOCA, or “ischemia with no obstructive coronary arteries,” describes conditions where patients have reduced blood flow to the heart, but without the blocked arteries typical of CAD. The most common forms of INOCA are coronary microvascular disease (CMD), also called small vessel disease, and coronary artery spasm (CAS).
Unlike coronary artery disease, which affects the heart’s larger arteries, CMD involves the heart’s smallest blood vessels. When the walls of these tiny vessels become damaged, they struggle to deliver sufficient oxygen to the heart, causing spasms that typically present as chest pain. Remarkably, more than half of women who experience chest pain have dysfunction in these tiny vessels rather than in their larger arteries. Despite its higher prevalence in women, INOCA remains difficult to diagnose in both men and women, leaving patients to navigate a healthcare system ill-equipped to detect conditions beyond traditional CAD.
Diagnosing INOCA remains a significant challenge in providing women with access to care. Common diagnostic tools like resting electrocardiograms or echocardiography often fail to detect microvascular dysfunction, and more accurate tests such as coronary function tests require invasive and expensive procedures, often involving injection and catheterization.
Andrea’s Project: Diagnosing INOCA in Women
The challenge of reaching a diagnosis is deeply personal for Women’s Health Research at Yale Fellow Andrea Rix. At just three months old, Andrea underwent open-heart surgery to repair a congenital heart defect. Two decades later, when she developed concerning symptoms—shortness of breath and chest pain—her healthcare providers were puzzled by this sudden deterioration. Through a series of inconclusive appointments and tests, Andrea experienced the uncertainty of knowing something was wrong with her health but not having answers or a clear treatment path forward.
This personal experience with diagnostic uncertainty now energizes Andrea’s research with Dr. Samit Shah, a Yale interventional cardiologist whose pioneering work on INOCA is transforming cardiovascular care for women.
Together, Andrea and Dr. Shah are working to address a fundamental gap in cardiovascular medicine: The standard questionnaire currently used for assessing ischemic chest pain, developed in 1994, was validated on a population of 95% men. By using data collected from Dr. Shah’s female patients with confirmed INOCA diagnoses, Andrea is helping Dr. Shah develop an updated questionnaire that more accurately captures the full spectrum of cardiovascular symptoms in women.
The team hopes their more inclusive, holistic questionnaire—one that considers physical symptoms alongside changes in quality of life and psychological factors—will improve how patients' symptoms are assessed and help them access more personalized, comprehensive treatment.
Zaharaa’s Project: Understanding the Treatment Gap in Women’s Heart Care
While Andrea focuses on improving diagnostic tools, Zaharaa Altwaij, another excellent colleague within the Women’s Health Research at Yale Fellowship, addresses the other side of the equation: treatment of those who are diagnosed. Under Dr. Freed’s mentorship within the program, Zaharaa is investigating the following question: why do some women refuse treatments that could save their lives?
Recent research has repeatedly shown that women face a double burden in cardiovascular care. Not only are they underdiagnosed, but they are also undertreated—less likely to receive beneficial medical procedures, less likely to be counseled by a healthcare professional to reduce cardiovascular risk factors, and less likely to be prescribed medication. This pattern of undertreatment spans the wide spectrum of cardiovascular care—from preventive interventions to emergency treatments.
Use of statins is a particularly concerning example of this treatment gap. By lowering levels of unhealthy cholesterol, statins prevent buildup of cholesterol in the arteries. These medications have been proven by numerous studies and years of clinical experience to reduce the risk of a heart attack and improve cardiovascular health, with a review of 40 studies finding that they reduce deaths from cardiovascular disease by 21%. And yet, despite their proven efficacy, women are less likely than men to be prescribed statins, even when facing similar conditions.
However, as Dr. Freed emphasizes, the issue extends beyond prescribing patterns. Even when statins are prescribed, many women are choosing not to take them and are twice as likely as men to discontinue use. Zaharaa’s project this year is to figure out why.
Adverse effects (“side effects”) of these drugs likely play a significant role in this hesitancy, with studies showing that women more frequently than men report adverse reactions, such as fatigue or muscle pain. Meanwhile, statins have also gained a negative reputation through online health forums and medical publications, exemplified by provocative headlines such as a 2007 study titled “Should women be offered cholesterol lowering drugs to prevent cardiovascular disease? No.”
Dr. Freed finds this pushback ironic. She explains, “Statins were the first cardiac medications to include women in the studies. It wasn’t in the same proportion as men, but actually women were included from the beginning. So it’s odd that statins get picked on more than anything. That’s not to say there aren’t adverse effects from statins. There are…No medicine is perfect. Everything is potentially going to have an effect that people don’t like. But, with statins, it’s no worse than the other medicines we use. But they have gotten kind of the bad rap on the Internet.”
Conclusion
Zaharaa’s research provokes an important question not only about the barriers women face in receiving care but also about the cultural forces that inform their health decisions. In a time when health headlines appear constantly on our screens, women face the challenge of making decisions about their health while sorting through a barrage of contradictory warnings and recommendations that seem to change daily.
The research projects being conducted by Andrea and Zaharaa are important contributions to women’s heart health precisely because they are willing to ask these difficult questions that have long gone unaddressed. Hopefully, with more research and collaborations like theirs, Andrea and thousands of other women will benefit from a healthcare system that recognizes and addresses women’s unique cardiovascular needs, giving them answers past generations were too often denied.
Ultimately, as Dr. Freed reminds us, “The best approach is to treat everybody the same in that you listen to everybody as they tell you about their symptoms and you work them up appropriately. You're not assuming that it's a woman's anxiety and a man's heart. Just treat everybody like their heart health may be at risk until proven it either is or it isn’t.”