Why Heart Disease Research Still Favors Men

Published in partnership with The Fuller Project, a nonprofit newsroom dedicated to the coverage of women’s issues around the world.

Katherine Fitzgerald had just arrived at the party. Before she could even get a drink, she threw up and broke out in a sweat. “I was dizzy. I couldn’t breathe. I had heart pain,” Fitzgerald says.

She knew she was having a heart attack.

What she didn’t know then was that the heart attack could have been prevented. Fitzgerald, a health-conscious, exercise-loving lawyer, should have been taking statin drugs to stop the buildup of plaque in her arteries that caused the heart attack and two others that followed.

Fitzgerald’s case illustrates a dangerous gap in medical care between men and women. While they are equally likely to suffer heart attacks, women are more likely to die from theirs. It’s one of the many symptoms of the medical system’s neglect of women.

Life-saving statins, like so many other medications, have been developed based on clinical trials that primarily recruited men. As a result, many women like Fitzgerald don’t receive prescriptions for the drugs that could help them the most, says Dr. Laxmi Mehta, director of Preventative Cardiology and Women’s Cardiovascular Health at The Ohio State University.

“There were a lot of trials. But women weren’t included as much,” says Mehta, who serves on the American Heart Association’s Research Goes Red Science Advisory Group. When women need treatment for heart conditions, she says, “we are assuming we are providing the best care based on data from men.”

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More than 30 years ago, Congress directed the National Institutes of Health to include as many women as men in clinical trials. But while some progress has been made, equity remains elusive. And that’s dangerous for women. “Since 2000, women in the United States have reported total adverse events from approved medicines 52% more frequently than men, and serious or fatal events 36% more frequently,” research firm McKinsey & Company said in a report released in January.

Now, the Biden administration is taking a run at it.

Last year, the administration established a White House Initiative on Women’s Health Research and, in February, it announced it would be dedicating $100 million to the newly formed Advanced Research Projects Agency for Health (ARPA-H) to spearhead efforts to increase early stage research focusing on women.

“For far too long, scientific and biomedical research excluded women and undervalued the study of women’s Health. The resulting research gaps mean that we know far too little about women’s Health across women’s lifespans, and those gaps are even more prominent for women of color, older women, and women with disabilities,” Biden said in an executive order signed in March.

Heart disease should be a bright spot in this black hole of medical research. It was the recognition in the 1980s that heart disease was killing women at similar rates to men that kickstarted passage of the 1993 law requiring equity in clinical trials. The American Heart Association has spent decades funding research and leading awareness campaigns about women’s risks.

But gaps persist, says Dr. Martha Gulati, president of the American Society for Preventive Cardiology and a cardiologist at Cedars-Sinai Hospital in Los Angeles. “We don’t get represented in trials,” Gulati told a seminar sponsored by the Society for Women’s Health Research in February.

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One example: Dr. Safi Khan of West Virginia University and colleagues reviewed 60 trials of cholesterol-lowering drugs conducted between 1990 and 2018. Not even a third of the people enrolled—28.5%—were women, they reported in JAMA Network Open in 2020. The trials’ findings likely did not accurately represent the public as a whole, they say.

“Medical research is several steps behind on women and heart disease, and that is a major contributor to ongoing ignorance about the problem on the part of both the public and a range of medical professionals,” says Dr. Harmony Reynolds, a cardiologist at NYU Langone Health. “Everywhere along the way, there is different treatment for women, and there is some bias there.”

Statins have been widely described as wonder drugs, lowering the risk of major heart events such as heart attack or stroke by about 25%. Women are less likely than men to be offered these drugs. And when they do take them, women are more likely to stop using them because of perceived side effects. But no major study digs into the actual rate of side effects among females, or what might lie behind such differences.

Further studies might uncover additional benefits, says Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. There are hints that statins might lower a woman’s risk of dying from cancer, including ovarian cancer.

Failure of recognition

Fitzgerald was 60, had higher-than-optimal blood pressure, unhealthy cholesterol levels, and a family history of heart disease, says Reynolds, Fitzgerald’s new cardiologist. “Katherine had multiple risk factors. Many of my patients are told their blood pressure and cholesterol are ‘borderline’ when really they should be treated,” she says.

Doctors often blame women for failing to recognize their own heart disease symptoms, but the evidence shows medical professionals miss them, too. 

The symptoms of heart attacks in men are widely known: crushing chest pain, a telling sensation in the left arm, or sudden collapse. Women, on the other hand, often feel nausea, jaw pain, or lightheadedness,

Fitzgerald did recognize her symptoms. At the party where she suffered her first heart attack, she begged for an ambulance. But other guests, including a physician friend, said they didn’t think she needed medical attention.

When paramedics finally arrived, they, too, dismissed her fears and diagnosed a panic attack. They sent her home. “If I had been a man, there is no way the paramedic wouldn’t have taken me to the hospital and I wouldn’t be in the mess I am now,” Fitzgerald says.

Fitzgerald waited two days to visit an emergency room. By then, some of her heart muscle had died. She received two stents to hold open clogged arteries, but suffered two more heart attacks in the following months. She now stays out of the courtroom and sticks to less-stressful desk work.

“I take care of all these young women with heart attacks and I hear so many stories about people saying they were ignored,” says Reynolds.

Waiting for attention

The problem is not just anecdotal. Reynolds and colleagues studied the problem by looking at more than 29 million emergency room visits by people under 55 reporting chest pain. 

“In that study we show young women coming in with chest pains and they are waiting longer to be seen,” Reynolds says. “The women are waiting too long and women of color were waiting even longer. So we know there is some subtle bias there.”

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Doctors can use risk calculators to try to forecast a patient’s future likelihood of heart disease and treat accordingly. But Dr. Stephanie Faubion, medical director of the Menopause Society, says they do not work well for women.

“That is because we are still using those that were developed and made for men,” says Faubion, who is also director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

Women have many specific heart risks. They have smaller coronary arteries, thinner heart walls, and suffer more heart damage from diabetes. Pregnancy can raise risks in various ways. Autoimmune diseases such as rheumatoid arthritis also add heart disease risks, and women are far more likely than men to have these conditions. 

Women who start menstruation early, or who reach menopause early, have higher heart disease rates. Birth control pills can raise the risk for blood clots, strokes, and heart attacks.

Perhaps the most recent instance of women being left out of heart disease research can be seen in the trials of highly popular diabetes drugs such as semaglutide, sold under the brand names Ozempic and Wegovy.

The drugs cause dramatic weight loss, which made researchers wonder if they might lower heart disease rates, too. They do, according to several studies, and the U.S. Food and Drug Administration now approves their use to prevent heart disease.

But none of the weight-loss trials, published in prestigious medical journals such as the New England Journal of Medicine and the Journal of the American Medical Association, break out separate data on men and women. And while the weight-loss studies did include far more women than men, many of the follow-on heart disease trials did not.

“They report the sex. They report ‘we have this many men, this many women,’” says Faubion. “They didn’t disaggregate the data on sex so they don’t know if it works better, the same, or worse in women than it did in men.”

Left out

Dr. Robert Kushner, a professor of medicine at Northwestern University who led some of the weight-loss studies, says he was surprised at the discrepancy between the enrollment of women in the obesity trials of semaglutide—in which about three-quarters of volunteers were women—and in the heart disease trials, in which women represented fewer than 28% of participants.

He says researchers recruited people already being treated for heart disease. “Predominantly, the ones who are getting care and being seen around the world were men,” Kushner says.

Kushner says he has yet to analyze results in his trial of semaglutide and weight loss by sex.

Missing out on breakthroughs

Harvard Medical School’s Manson has been sounding the alarm on discrepancies in medical research for decades.

“Raising more questions is what leads to the major breakthroughs,” she says.

Yet she has been mostly ignored, even though she helped lead the largest-ever study looking specifically at women’s health—the Women’s Health Initiative, which involved more than 160,000 women over 15 years.

The study was initially designed to see if hormone therapy in women past menopause could reduce their rising rates of heart disease and breast cancer. It also later looked for evidence of effects on bone strength, other cancers, dementia and quality of life.

The first results were startling. The hormone therapy used in the trial raised the risk of breast cancer and failed to reduce heart disease.

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“Many clinicians stopped prescribing hormone therapy altogether. Many women tossed their pills and patches,” Manson says. When the trial started, an estimated 40% of menopausal women used hormone therapy. Now, Manson estimates, only about 4% do.

The study has since been shown to have been flawed. The average age of the women in the study was 63—well past menopause. And the hormone therapy used was a high-dose hormone distilled from horse estrogens.

Later studies have indicated that lower doses and different formulations such as patches, given to women as they start menopause, may be much less harmful while reducing hot flashes, sleep loss and other symptoms. “These formulations don’t go to the liver and should be safer,” Manson says. There’s also tantalizing evidence they may lower the risk of heart disease.

Meanwhile, the lack of data means that many women who would benefit from hormone therapy are not getting it, says Faubion. 

Back in 1993, it took the considerable efforts of Dr. Bernadine Healy, the first female director of the NIH, to persuade Congress to directly fund medical research on women and heart disease.

“They are just not going to do that again. It’s too expensive,” says Faubion.

Biden asked Congress for $12 billion to improve research planning and to set up a network of research centers to focus on women’s Health. And NIH has encouraged requests for money to study women in particular.

But when Congress passed a last-minute spending bill in March, it kept Health funding flat. The Republican-led House did not address Biden's request or allocate any cash for additional research into women's Health.

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