How Is Heart Disease Different in Women?

A woman in her 50s wakes up feeling nauseous. Dismissing it, she moves through her day, feeling a bit fatigued during her morning walk, even short of breath. But when she experiences shooting pain in her left arm, her friends urge her to get medical attention, and she goes to the emergency room. She is diagnosed with a mild heart attack and undergoes a battery of tests—only to be told her arteries look perfectly normal, and they don’t know exactly what caused the heart attack. So, she goes home unsure if she has heart disease.

For years, that woman’s experience wouldn’t have merited a second thought. That’s because our understanding of heart attacks was, until recently, primarily based on data gathered from men. And when men have heart attacks, they typically have chest pain due to blockages in the heart’s three main arteries.

But doctors are learning how different heart attacks and heart disease can be in women. For instance, their symptoms can be as subtle as a suspected case of heartburn with some dizziness and nausea, and testing may show none of those blockages. Instead, the small arteries may not function properly, or a large artery may have had a spasm.

We spoke with Yale Medicine cardiologist Erica Spatz, MD, MHS, a clinical investigator for the Yale Center for Outcomes Research and Evaluation (CORE), which focuses on health care quality, and interventional cardiologist Samit Shah, MD, PhD, about how the knowledge of women and heart disease is changing.

Chest pain is actually the most common symptom in both sexes, but women may not experience intense chest pain—the feeling of heaviness, like an elephant sitting on the chest. They may instead have tightness or a dull ache in the chest, and they may have shortness of breath, jaw pain, or nausea.

“Sometimes, women’s symptoms are more diffuse, like dizziness, clammy skin, or unusual fatigue when they are going for a walk or doing other physical activity. Symptoms may also occur during times of stress. All of this may result in both women and their doctors not recognizing the symptoms and missing the seriousness of the condition,” says Dr. Spatz.

Sometimes. A heart attack is typically caused by a blockage in the heart artery, and most women who come in with a heart attack will have this classic finding, Dr. Spatz explains. But in a significant number of women presenting with signs of a heart attack, there is no blockage.

Dr. Shah knows this firsthand. He performs coronary physiology testing during a standard angiogram to detect the underlying cause of heart attacks and chest pain syndromes in patients without obstructive coronary artery disease. Most of his patients are women. In April 2022, Dr. Shah and his colleagues presented findings to the American College of Cardiology that showed a median time of more than six years between initial symptoms and an accurate diagnosis in 64 patients (48 of whom were women) who did not have blockages, and who were later diagnosed with an expanded procedure called coronary physiology assessment.

There is greater recognition that women have non-traditional forms of heart attack. “Some of our newer imaging tests and catheter-based assessments can reveal disease in the small arteries of the heart [known as microvascular dysfunction], which can lead to heart attacks,” says Dr. Spatz. “In other cases, a cardiac event may be due to a rupture of a plaque or a spasm of the artery, which is dynamic. The rupture or spasm may have occurred at the time of the chest pain, but by the time women are in the catheterization lab, the problem has resolved and the artery looks normal.”

Microvascular dysfunction may go undetected, and the event may be dismissed as ‘not cardiac,’ Dr. Spatz explains, adding that this can also happen with a coronary vasospasm, which is a sudden tightening of the blood vessels that supply oxygen to the heart muscle; it is temporary but can be dangerous. “Doctors may attribute the symptoms to anxiety or a stomach-related problem,” she says. “Sometimes, women leave the hospital with a mixed message: ‘You had a heart attack, but the heart arteries were clean. Good luck.’”

The lack of a firm diagnosis can lead to uncertainty about treatment and prognosis. Women often feel unsure about whether to seek care the next time they have that kind of pain because doctors didn't find anything the first time, she adds.

Yes. Dr. Shah is leading a team to study how expanded diagnostic cardiac testing for women can help identify non-traditional forms of heart attack that are more common in women when major arteries are not blocked. Their testing includes a heart catheterization study that he says only a few hospitals in the country offer at this point. When an angiogram doesn’t show blockages, Dr. Shah injects a medicine called acetylcholine into the blood vessels that helps test for vasospasm. This is followed by testing for microvascular dysfunction with a specialized wire to assess the smaller heart vessels that carry most of the heart’s blood supply.

The team is studying 100 women over two years who are referred for coronary angiography to Yale New Haven Hospital and comparing the outcomes of patients who receive the standard care with those undergoing the new tests to detect coronary microvascular disease or coronary vasospasm. The goal is to show the value of using them so they can become the standard of care for patients with reduced blood flow without obstruction.

A proper diagnosis also means better treatment, Dr. Shah says, and this includes the prescribed medications—for instance, patients with microvascular disease respond better to different medications than those with coronary vasospasm. “Our advanced coronary physiology testing can reveal the diagnosis and allow us to get patients on the right therapy,” he says.

In addition, Harlan Krumholz, MD, the director of CORE, led a large study aimed at understanding the experiences and outcomes of patients after a heart attack, comparing men and women. The study demonstrated several unique risk factors among women, including depression, poor social support, and low socioeconomic status. It also showed that women recover from heart attacks differently than men.

The research reviewed nearly 3,000 charts from the VIRGO study and found that one in eight women in the study did not have evidence of a classic heart attack and, in fact, did not fit into the traditional classification system for different types of heart attacks. So, they developed an alternative system called VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) to capture the types of heart attacks and the biological and pathological mechanisms that underlie them.

“The VIRGO study acknowledges that we often don’t know what caused the heart attack,” says Dr. Spatz. “This is important because it can open the door to further research and discoveries.” VIRGO isn’t in practice at this time, but the concept is out there, and more and more clinicians are attuned to women’s heart disease and employing newer detection approaches, she adds. Additionally, more studies are being done to evaluate prognosis and optimal treatment strategies for different types of heart attacks.

Estrogen is protective of the heart in the pre-menopausal years—it relaxes the arteries and promotes good cholesterol. “But as menopause approaches, estrogen declines, and we see more cardiovascular risk factors, such as high cholesterol and hypertension, in women,” Dr. Spatz says. “The incidence of heart disease in women starts going up around age 65—about 10 years later than in men—and that’s likely due to the lingering positive effects of estrogen.”

An ongoing question has been whether hormone replacement therapy (HRT) protects against heart disease. HRT is used to replace the estrogen a woman’s body stops making after menopause; in women who still have their uterus, it’s usually prescribed with another hormone called progesterone. In the 1980s and 1990s, estrogen was used liberally to prevent heart disease in women. Then the Women’s Health Initiative, a series of clinical studies initiated by the National Institutes of Health, tested the effects of estrogen alone and found a higher risk of heart attack and stroke.

More recently, the pendulum has been swinging back—but not fully. When prescribed properly, estrogen is considered mostly safe and may help lower cardiovascular risk, but only in women younger than 60 or who are less than 10 years into menopause and do not have heart disease.

Statins are medications that lower LDL (bad cholesterol); they are a mainstay for preventing heart attack and stroke—resulting in about a 30% to 40% reduction in risk. One reason there is backlash is that statins are recommended to so many people, especially as they get older, Dr. Spatz explains. “Our job as cardiologists is to figure out who is and is not likely to benefit from statins because they were never going to have a heart attack in the first place,” she says. There is also concern about side effects such as muscle pains. Although these can occur, we now know that they are relatively uncommon, occurring in less than 5% of people, she adds.

Historically, women have been under-prescribed preventive medications because doctors see women as being at low risk for heart disease. While this is sometimes true, doctors need to ask about a family history of heart disease, preeclampsia (characterized by high blood pressure and signs of damage to another organ system during pregnancy), early menopause, and other risk factors that increase a woman’s risk for heart disease, which may change the value equation for taking a statin, Dr. Spatz says, adding that for women with established heart disease, there is a strong recommendation to take a statin since there is a big reduction in risk of future heart attacks.

“Ultimately, we need to engage women in shared decision-making, which involves discussions with their doctor about their personal risk for developing heart disease and the potential for statins to lower that risk,” Dr. Spatz says, adding that some of her research is aimed at encouraging these conversations with women around what contributes to cardiovascular risk and how much statins can impact that risk.

Women are about as likely as men to develop high blood pressure at some point during their lives, according to the Centers for Disease Control and Prevention (CDC)—and they are more likely than men to have it over the age of 65. Menopause has been associated with a twofold increase in risk for the condition.

Coronary microvascular disease, one of the difficult-to-detect conditions that many women develop, may be associated with high blood pressure, Dr. Shah explains.

“Hypertension is the most important risk factor we can control,” Dr. Spatz says. Yale New Haven Health Heart & Vascular Center and Yale Medicine are working to improve blood pressure control with a strategic focus on the New Haven community, she adds. “We are collaborating with pharmacists and implementing more person-centered ways of monitoring blood pressure, including remote monitoring [measuring blood pressure at home] and telemedicine visits.”

Yale Medicine doctors also are working to identify and address barriers to poor blood pressure control—such as poor diet, financial stress, and transportation—and have expanded the program to include postpartum women who’ve had hypertension or preeclampsia and who are at risk for having high blood pressure after they deliver.

Broken heart syndrome, also known as stress-induced cardiomyopathy, is an acute but temporary condition that mimics a heart attack. It typically occurs in response to extreme emotional or physical stress, leading to chest pain, shortness of breath, and in some cases, heart muscle failure. While the syndrome also occurs in men, it is most common in post-menopausal women.

The good news is that most people who experience broken heart syndrome have a quick and complete recovery and no lasting damage. But scientists are still studying the long-term effects of this syndrome.

“We just wrapped up a grant from the Alpha Phi Foundation in which we conducted peer sessions with women about their cardiovascular health,” Dr. Spatz says. Together with an organization called the Patient Revolution, Yale Medicine providers facilitated conversations for women to better understand heart disease and to provide opportunities to think, feel, and discuss the personal factors contributing to their heart health. “The goal was to empower the participants with the knowledge and skills to have better discussions with their clinicians about their cardiovascular health,” she says.

“Women should expect a personalized approach and accept nothing less,” says Dr. Spatz. “Personalized medicine means taking the time to understand the patient—and how their biology and biography may contribute to their cardiovascular health.” Medical providers now use calculators to estimate people’s risk of developing a heart attack in the next 10 years, which is a good starting place, she adds.

Providers should also ask about diet, activity level, daily stressors, experience with depression and trauma, and general well-being, she says. It’s important to know about pregnancy experiences, including issues such as diabetes, preeclampsia, high blood pressure, or pre-term delivery, she adds. And it’s important to take a detailed family history of early heart disease occurring in a first-degree relative before the age of 60. More information may need to be collected through advanced lipid testing, a calcium score, and genetic testing.

“As a doctor, I want women to feel comfortable saying to me, 'Knowing what you know about me, what is my risk, and what can I do to modify my risk?' Then, we can work together to find a personalized plan,” says Dr. Spatz.

Information presented in this interview was supported by studies funded by Women’s Health Research at Yale (WHRY) and the Alpha Phi Foundation.