When Nancy Larko, aged 84, went to see her doctor in Meadville, Pennsylvania, earlier this year, she thought her stomach pains was the result of something she’d eaten. Her symptoms had begun on Friday afternoon, but Larko, unconcerned, didn’t contact her doctor until the following Tuesday, after four days of discomfort. Her doctor said that it was a gallstone, but nothing to worry about; he kept her in observation overnight, then sent her home on Wednesday afternoon.

No one seemed to have noticed that Larko had had a heart attack.

Soon after she got home on Wednesday, Larko began experiencing chest pains. This time, she called her family and her doctor immediately. At the hospital, she was told that she had had two heart attacks over the past five days—and the first one had created a hole in her septum between the left and right ventricles, weakening her heart and almost completely killing the bottom part of the muscle. Two days later, Larko died.

The fact that Larko and her doctors missed her first heart attack is not an unusual occurrence—thousands of American women with heart disease are misdiagnosed every year, often with fatal consequences. Heart disease is currently the number-one cause of death among women in the U.S., killing more than all cancers combined. While men are more likely to be diagnosed with heart disease, according to the American Heart Association, women still made up slightly more than half of all its fatalities in 2011, the most recent year for which data was available. Women are also more likely than men to die in the year following a heart attack. In part, these disparities can be traced back to a bias older than modern medicine itself.

In the 1700s, the heart was linked to emotion—a vestige from the days of Aristotle, who believed that the heart was the seat of all feelings, particularly anger. The Scottish surgeon John Hunter was one of those who linked heart disease to emotional excesses. His own fatal heart attack was caused, according to his doctors, by his angry temperament.

In the late 19th century, the influential Canadian physician William Osler challenged this idea, arguing that heart disease was caused by stress, not anger. The typical heart patient, he believed, was a “keen and ambitious man, the indicator of whose engine is always ‘full speed ahead’”—a “well ‘set’ man from 45-55 years of age, with a military bearing, iron-gray hair, and a florid complexion.” For Osler, heart disease was almost a badge of honor, the mark of a hardworking capitalist man.

For the next 100 years or so after Osler’s writing, that was the image that stuck. Throughout the 19th and early 20th centuries, doctors believed that the people most prone to heart attacks were of the type that Osler described: ambitious, successful, and most importantly, male.

It wasn’t until the 1950s that heart disease was linked to diet, exercise, and other physical factors rather than emotional causes—but even then, it remained a man’s condition. The American scientist Ancel Keys, who authored several landmark studies on diet and heart disease in the 1960s and ‘70s, used middle-aged men in most of his research, a pattern that repeated itself in many of the most important cardiology studies of the next few decades. For example, the 1982 Multiple Risk Factor Intervention Trial, one of the first to establish a link between cholesterol and heart disease, involved 12,866 men and no women; the 1995 Physicians’ Health Study, which found aspirin to reduce the risk of heart attack, involved 22,071 men and, again, no women.

The focus on men extended to medical education as well. “When we were taught about it at medical school [in the 1970s and ‘80s], no one explicitly said, ‘This is a man’s disease,’” said the New England Journal of Medicine editor Harlan Krumholz, who started studying heart disease in young women in the early ‘90s as a medical researcher. “The case studies at that time, 20 or 30 years ago, were focusing on the man as the prototype of the problem.” Krumholz recalled the iconic drawings of Frank Netter, arguably the most famous medical illustrator of the 20th century—Netter’s illustrations, which medical students still use to learn about human anatomy and a variety of diseases, only rarely depicted women with heart disease.

The absence of female subjects in medical textbooks and in research papers means many doctors simply didn’t know how to treat heart disease in women, or even how to recognize it. Symptoms can differ by gender: Men are likely to get chest pains when they’re having a heart attack, for example, but women may instead feel discomfort in the neck, jaw, shoulder, back, or arm. Many women also experience nausea, vomiting, or a feeling similar to indigestion, as Larko did.

In a study published last month, Krumholz and his colleagues found that women under 55, in particular, may have symptoms that fall outside what’s currently considered typical. Among the women they interviewed, Krumholz said, “Almost all of them reported that they almost had to convince people, almost ‘sell’ the idea that they might have something serious. So many were telling us that their symptoms had been going on for a while but were neglected by the health-care system.”

Other research supports this idea. One 2005 study, for example, found that women are less likely to get tests to diagnose heart-related illnesses. And in 1999, a survey of physicians published in the New England Journal of Medicine found that doctors are roughly half as likely to recommend cardiac catheterization, a test that determines the severity of heart disease, when the patient is female. The same survey also found that women are less likely than men to get bypass surgery or balloon angioplasty to unclog blocked arteries.  

Even so, the past two decades have seen some improvement. In 1991, the cardiologist Bernadine Healy became the first woman to head up the National Institutes of Health. Her appointment signaled a quiet but wide-reaching shift in how the medical establishment thought about women and heart disease: Under her leadership, the NIH began funding more studies focused on women with heart disease; meanwhile, campaigns like the American Heart Association’s Go Red for Women, founded in 2003, gathered momentum. In a 1991 editorial in the New England Journal of Medicine, Healy wrote: “Heart disease is also a woman’s disease, not just a man’s disease in disguise.”

But even with the increasing attention paid to heart disease in women over the past couple decades, it could still take some time to erase centuries of bias—not only within the medical community, but among women themselves. Many patients, like Larko, fail to realize that something is seriously wrong until it’s too late.

After Larko died, her grandson Evan Woods said, he talked to doctors and nurses about how his grandmother’s first heart attack could have gone undetected. Her symptoms were unusual, they told him; stomach pains weren’t enough to diagnose a heart attack. “How can they be unusual,” he said, “when it is more than half the population?”