Study reveals major differences between women and men in cardiovascular disease traits and treatment

University of Michigan Health System
Sunday, 9 November 2003

Women have more diffuse yet less obstructive blood vessel blockage, which leads to less aggressive treatment of symptoms, U-M researchers find

A new study shows just how different men and women really are when it comes to their hearts, that is. It also helps solve several mysteries about women and heart problems, and highlights the need for better treatment of the No. 1 killer of women.

The study, led by researchers from the University of Michigan Cardiovascular Center, shows that women who suffer chest pain or a heart attack are more likely than men with the same conditions to have only mild and more diffuse blockages in their major arteries. This means that for these individuals, their symptoms are most likely caused by blockages in smaller, less flexible vessels.

But even when men and women with similar rates of heart attacks were compared, the women were less likely to get aggressive drug treatment, according to the new results from the Global Registry of Acute Coronary Events being presented here today at the American Heart Association's Scientific Sessions 2003.

Since women's large blood vessels were more likely to be clear when examined via angiography, the authors think they may have found the reason why so many women leave the hospital without a firm diagnosis and with a less aggressive therapy regimen after experiencing acute heart symptoms.

And, the finding may explain a long-known but mysterious disparity between men and women in the rate of angioplasty and bypass surgery, which are most often done only after severe blockages or narrowings are spotted on an angiogram.

But the researchers were especially surprised by the disparity in drug therapy, including the use of aspirin, beta-blockers and clotbusters in the hospital, and aspirin and beta-blockers at discharge. Such drugs are recommended for nearly all people who suffer heart attacks.

"The question of whether there is some sort of bias against women in heart treatment has been around for some time, and in fact our data do show a bias against giving women more aggressive therapy," says Sujoya Dey, M.D., the U-M cardiology fellow who led the analysis.

"But, our findings also suggest the bias may be understandable, because women's coronary artery disease on average appears to be different," she adds. "It's more likely to be diffuse, occurring in vessels too small for angiography, angioplasty or bypass."

Explains Kim Eagle, M.D., the senior author on the study and clinical director of the U-M Cardiovascular Center, "This actually may help debunk the theory that women are being offered less treatment because of bias based solely on their gender. The bias may stem from the disease."

And, he adds, "This means medical management, with aggressive drug therapy, becomes even more important for women. We still have a way to go on making sure both men and women get the drugs that can help them."

Coronary heart disease, which includes heart attack and angina, is the single leading cause of death among American women, killing 254,630 in the year 2000, according to AHA. About 210,000 women will have a heart attack this year, and angina affects 4.1 million women (compared with 2.5 million men). In all, 6.6 million American women alive today have a history of heart attack, angina or both.

But still, Dey and Eagle say, women tend to think of heart disease as a man's problem.

The study examined data from 33,202 men and women who enrolled in the GRACE trial between April 1999 and August 2003, at 100 hospitals in 14 countries. Eagle, Dey and researchers from Austria, England, New Zealand, Australia and the University of Massachusetts prepared the report.

GRACE is an observational database of patients hospitalized with suspected acute coronary syndromes, which includes several kinds of heart attack and unstable angina (chest pain). The data collected include demographics, disease symptoms and presentation, in-hospital management and outcomes.

The researchers focused on data from 10,500 of the patients who underwent coronary angiography. This approach, common in the U.S. but less common in other countries, sends a tiny tube called a catheter into the groin, up through a patient's arteries and into the vessels surrounding the heart. The catheter releases dye that's visible on X-ray images allowing doctors to see blood vessels and determine if they might be blocked or narrowed.

The extent of blockage, called stenosis, is classified according to the percentage of the vessel's cross-section that has been filled by plaque or clots lining or clinging to the vessel's inner walls. For the study, patients were considered to have mild stenosis if less than 50 percent of a major blood vessel's cross-section was blocked, and to have coronary artery disease if they had a 50 percent or greater blockage in at least one major vessel.

The study also looked at the levels of certain enzymes that can be measured in the blood to determine if a heart attack really occurred. Women in the study tended to be older and to have more health problems than the men, but their rate of cardiac enzyme release was about the same.

Despite similar rates of enzyme release, women were more than twice as likely as men to have normal or mild stenosis evident on their angiograms.

"This lack of clear evidence of blockage, even in the presence of elevated enzyme levels and a positive stress test, may be what causes so many doctors to scratch their heads about female patients with chest pain," says Eagle.

Women were also statistically less likely than men to undergo percutaneous intervention (PCI) such as angioplasty, or bypass surgery. This may make sense in light of the fact that they were less likely to have severe obstructive blockages on their angiograms the kinds of blockages targeted by such therapies. Not surprisingly, women also had a lower rate of previous PCI or bypass than men.

Overall, people of both sexes who had normal-looking vessels or mild stenosis were less likely than those with more advanced disease to get either interventional or medical therapy.

But when women and men with the same mild level of stenosis were directly compared, the women were statistically less likely to get in-hospital aspirin. They were also less likely to be prescribed beta-blockers on discharge.

Six months after discharge from the hospital, there was no difference overall between the genders in the number of patients who had experienced one of the following: death, a non-fatal heart attack, a stroke or other cerebrovascular accident, or readmission to the hospital. But women who had had an angioplasty were slightly more likely than men to meet a combined endpoint that included all those outcomes.

The bottom line, says Dey, is that there's a difference in disease and treatment that both doctors and patients need to pay attention to.

"Women may on the whole have more mild-looking disease than men, but even when they had similar-looking disease they were still under-treated," she says. "If your angiogram looks the same you should be getting the same medical therapy. Even the differences in age between the two gender groups shouldn't make a difference in medical management, though it may affect the use of interventional procedures."

Over all, Eagle emphasizes, the findings mean that physicians should be more aggressive with prescribing medications to women with signs of heart disease, because those drugs can help keep blood vessels clear, prevent clots, and keep vessels from hardening.

And women should speak up for themselves, adds Dey. "Believe yourself and your symptoms, and bring them to the attention of your physician to figure out how to help you," she says. "Don't be afraid to ask what else they could be doing for you."

As for the root cause of the difference between the genders in which vessels get blocked and how blocked they get, Dey and Eagle say only more research will tell. Simply the fact that women's bodies and blood vessels are smaller and therefore more vulnerable to blockages in tiny vessels may account for some of it but there may be something going on at the molecular level too.

And, the researchers note, the findings point to the urgent need for a new imaging method or other way of seeing blockages and narrowing in smaller blood vessels.

In the meantime, they hope to evaluate the GRACE data and other data they're collected from U-M patients, to study the effect further. They hope they can develop a risk-prediction tool that will tell doctors which women are most likely to have small-vessel disease and resulting symptoms.

Reference: American Heart Association Scientific Sessions, "Coronary Disease in Women is Different from that in Men with Acute Coronary Syndromes" Abstract 3247, Abstract poster session 97.1, Sun., Nov. 9, 8:30 a.m., Hall A.

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