On that November Sunday in 2015, Stephanie Thomas Nichols was 40 miles into her drive home to Townsend, Del., from her vacation cabin in Western Maryland when she felt an odd sensation in her upper body.

“No pain, just pressure, heaviness,’’ recalls Nichols, who owns a software company. She couldn’t catch her breath. Within minutes, her left arm went numb.

She remembers thinking, “Something’s not right here.” She pulled off I-68 at the next exit, near Cumberland. She asked a man working in his yard where she could find a hospital, and he led her straight to an emergency room.

Nichols, then 47, was having a heart attack.

[‘The night my heart stopped beating’]

She has no family history of heart disease, she doesn’t smoke, and her cholesterol and blood pressure are normal. She doesn’t have diabetes, and she experiences little stress. Tests showed clear arteries with no blockages, the most common cause of heart attacks. “I left them shaking their heads,” she says.

In all likelihood, her heart attack was caused by one of several conditions that tend to afflict women more often than men. Those conditions produce less dramatic symptoms, such as the chest pressure that Nichols felt, rather than stunning pain, so they may be overlooked by doctors who mistake them for lesser ailments. Researchers still are trying to better understand these disorders, especially why women are so prone to them.

Nichols’s physicians believe she may have suffered a temporary coronary artery spasm, which is more common in women who have heart attacks than in men, or a minor blood clot. Both are capable of stopping blood flow to the heart. Coronary arteries power the heart by carrying oxygen-rich blood to the heart muscle.

In the United States, 1 woman in 4 dies of heart disease, the same proportion as in men, according to government agencies. The American Heart Association puts the toll for women higher, at 1 in 3. In fact, coronary heart disease, which is the most common type of heart disease, is the No. 1 killer of both men and women in the United States.

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Research has begun to recognize “that men and women are different in many ways besides our reproductive systems,” says Janine Clayton, director of the office of research on women’s health at the National Institutes of Health. This is especially true with heart disease, where the differences between men and women can be striking.

The most frequent sign of heart attack in a man is chest pain. Women also experience chest pain, but they are more likely than men to have nausea, shortness of breath, dizziness, indigestion, pain in the shoulder or jaw or even in the back, and fatigue that can persist for days, according to the National Heart, Lung, and Blood Institute.

Also, as with Nichols, women more often than men have heart attacks where there is no coronary obstruction, and the danger is hard to detect ahead of time, according to the NHLBI. In such cases, plaque doesn’t accumulate to form major blockages; rather, it spreads evenly throughout the walls of blood vessels, producing “clear” tests. Nevertheless, research indicates that these women are at a high risk of having a heart attack that results from a narrowing in the very small arteries of the heart.

“Women’s cells and lungs are different from men’s,” Clayton says, and women have smaller coronary blood vessels. “If you have multiple very small blood vessels involved [in a heart attack],” she adds, “it won’t give you crushing chest pain.” But it may give you coronary microvascular disease, which affects the walls and inner lining of tiny blood vessels that branch off from the larger coronary arteries. These small vessels typically do not have plaque, but they sometimes trigger spasms and decreased blood flow to the heart muscle, impairing the heart’s ability to pump blood throughout the body, according to the American Heart Association.

[A $10,000 blood test?!? Yes, really.]

Coronary artery spasms such as those Nichols probably suffered occur “when the muscle that surrounds the wall of the artery has a spasm . . . obstructing the flow of blood, although it is not a typical obstruction,” says Nakela Cook, chief of staff to the director of the NHLBI.

Clayton agrees, saying: “Women tend to have a kind of heart disease where the vessels go into spasm for a short period of time, then go back to normal. If you have a stress test, for example, and you’re walking on a treadmill and you aren’t in spasm, your test will be normal.”

Women also are vulnerable to takotsubo cardiomyopathy, a type of heart muscle weakness also known as “broken heart syndrome,” which was first described in 1990 in Japan and is related to extreme emotional stress. More than 90 percent of reported cases are in women age 58 to 75, according to Harvard Medical School. “It’s rare, but when it does occur, it’s predominantly among women,” Cook says.

Finally, spontaneous coronary artery dissection, or SCAD, another condition more common to women, occurs when an artery that supplies blood to the heart spontaneously tears, sometimes forming either a blood clot or a flap near the tear, causing acute, very intense pain, according to Cook.

SCAD may be related to fibromuscular dysplasia, a disorder that results in reduced blood flow to several organs, not just the heart, according to Pamela Ouyang, director of the Johns Hopkins Women’s Cardiovascular Health Center.

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“A high percentage of people [with SCAD] have this abnormality in other blood vessels,” she says. “It’s much more common in women than in men.”

It also may have a hormonal connection. “Men are much less likely to get a tear,” Cook says. “It seems to show up at times of higher levels of estrogen, such as during pregnancy. We are trying to see if hormone therapy can also trigger this. We have seen it in older women, although we don’t necessarily think the mechanisms are the same.

“The question that still remains is how hormones matter during the course of a life span,” Cook adds. “It’s an active area of investigation that really speaks to the need to have specific studies in women asking sex-specific questions.”

To be sure, hormones long have been the focus of scientific scrutiny in women and heart disease, particularly because women tend to get heart attacks later in life than men, typically after menopause; they also live longer than men. The hormonal relationship may be a factor in why Nichols had a heart attack at such a young age: She underwent early menopause, at 42.

“It’s clear that premenopausal women have less cardiovascular disease than men, but once they become post-menopausal, they become equal to men,” says Elizabeth Murphy, head of the NHLBI’s cardiac physiology section. The thinking has been “that there is something protective about estrogen.”

(The Women’s Health Initiative, which has followed nearly 162,000 women since 1993, concluded there was no protective effect against heart disease from hormone replacement therapy, or HRT. Scientists speculate, however, that this finding may be the result of timing: Many women in the study had been menopausal for a decade or longer before beginning HRT. Subsequent research indicated a “critical window” when hormone replacement therapy could be protective in women age 50 to 59 while harmful for women age 70 to 79 who begin HRT later. )

Scientists think the estrogen-related protection occurs because, among other things, the hormone stimulates an increase in an enzyme that produces nitric oxide, which promotes a healthy vascular system. “It seems to be involved in helping the coronary arteries dilate to bring more blood to the heart, and in regulating ion channels, which are important for how the heart beats,” Murphy said. She and others are studying whether this estrogen “signaling” changes with age and becomes less effective, possibly producing substances “that are detrimental rather than beneficial,” she says.

Historically, heart disease was regarded as a disease of men, with most studies conducted solely on them. This is no longer the case. But old assumptions persist among many clinicians and women, experts say.

“Doctors need to raise their index of suspicion when women have these vague symptoms,” Clayton says. “If we have evidence that sex matters, which we do, we need to act on that knowledge when making treatment decisions.”

Women, too, never should dismiss odd or suspicious symptoms as no cause for concern. “It’s important for a woman to recognize she is having a heart attack because time is critically important,” Ouyang says.

Nichols agrees. She knows she was smart to act when she did, and she realizes how lucky she was. “Don’t think I don’t think about that every morning,” she says.

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