Phases of the Heart

Cardiovascular Disease in Women

By Kathleen Yount

When you’re 17, it’s hard to imagine that the fries and Coke you’re enjoying with your friends could mean the difference between bouncing a grandchild on your knee at age 70 and dying before your first child graduates from high school. At 17, most girls haven’t given much thought to having kids at all—a teenage brain simply isn’t built to worry about health consequences 20 or 40 or 60 years down the road.

But between the soda and fast food something has to give, because heart disease is still killing women at a rate that outpaces all other diseases—as it has throughout the last century. And for most women, the first steps toward heart disease are taken in their teens.

“Everybody’s always looking for new ways to detect heart disease in women,” says Bonnie Sanderson, Ph.D., manager of cardiac rehabilitation at UAB Hospital. “But the bottom line is that most cases of heart disease can be prevented if we just focus on lifestyle factors: requiring physical education in schools, teaching our kids healthy nutrition, reducing obesity, and preventing smoking. If that’s established early in life, then the medical ambiguities of what to do later on will no longer be the big issues they are today.”

Researchers at UAB have been exploring those issues by taking part in a major study of women and heart disease—the WISE (Women’s Ischemic Syndrome Evaluation) study. But participating UAB cardiologist Vera Bittner, M.D., says she wants to focus on more than just the findings stated in the report, which was published in February. She and Sanderson want to talk about what’s not being said.

“We’ve all been studying and arguing about which test to use to detect heart disease in women in their thirties or forties,” says Bittner. “This research is very important, but it’s not changing the fact that the women in our study may have been 100 percent overweight for 30 years. We’re trying to find disease markers, which we must do, but we must also address the simplest solution: preventing disease by making lifestyle changes.”

Setting the Trends

Among its many nasty attributes, smoking is a major contributor to another condition that is underdiagnosed in young women: hypertension.

One lifestyle choice that remains all too fashionable among young women is smoking. “Even though public-health messages about smoking are reaching other groups, younger women are not getting the message,” says UAB cardiologist Salpy Pamboukian, M.D. To be clear, the rate of smoking among women is still lower than that of men, but the gap is shrinking. And according to the 2001 Surgeon General’s report, women who smoke double their risk of heart disease.

Among its many nasty attributes, smoking is a major contributor to another condition that is underdiagnosed in young women: hypertension. “A lot of women, unless they go for yearly physicals, are not getting their blood pressure checked,” says Pamboukian. “And because it’s asymptomatic, young women may not even realize they have hypertension. They should be getting screened in their thirties, twenties, or even teens, especially if they have positive family histories.”

The African-American community is particularly vulnerable to hypertension. “Even if they’ve been diagnosed with high blood pressure, African Americans often aren’t adequately treated,” says Pamboukian. “We hear people say, ‘I’ve been told I have high blood pressure,’ but they’re not on medication.” The effects of untreated hypertension may not be seen until a woman is 50, but if she’s been hypertensive since her teen years, she could be diagnosed with heart disease much earlier. “I’ve had patients in their 20s with congestive heart failure,” says Pamboukian. “And it’s because they’ve had high blood pressure for so long.”

Marriage, Motherhood, Role-Modeling

It’s been another long and grueling day at the office. Before you go home you have to pick up the kids: one from school by 5:30 and the other from day care before 6. Your palace awaits you: a house full of laundry, a bathroom that needs cleaning, dinner that needs preparing. And on top of that, the dog is sick. Will you be able to find time to take him to the vet tomorrow? What about your dentist appointment next week? What about tonight’s dinner? It could be that Pizza Hut is in your family’s feeding future.

Meanwhile, the treadmill you put in your bedroom—hoping it would make it easier for you to fit some exercise into your day—well, it makes a great place to hang the shirts that still need ironing and pile the socks that need sorting.

In most households, the woman still runs the domestic show, and for many women that means stress. “Lots of women neglect their health because they’re busy looking after everybody else,” says Pamboukian. “They aren’t going to their doctors for well-woman visits or having their regular screenings. And a lot of women overeat when they have young children; when they take their kids to fast-food places, they end up eating the same food the kids eat—and sometimes finish off whatever the kids leave on their plates.”

This is a critical time to maintain a healthy diet and to exercise, but sadly, most young mothers tend to let those aspects of their lives slide. “Everybody has stress,” says Sanderson. “What’s important is how you deal with the stress. If you are active and you eat right and you don’t smoke, you’ll be better able to respond and to cope with stress—and enlist more productive problem-solving actions.”

Stress and a jam-packed schedule may also cause women to ignore the early signs of heart disease. “So many physicians see patients who say, ‘I’ve been having this symptom for two years, but I just ignored it because I assumed it was heartburn,’” says Pamboukian. “Women probably ignore their symptoms more often than men—and even when they do seek medical attention, they aren’t always taken seriously. When a woman comes in complaining of symptoms of heart disease, her doctor might tell her that it’s just stress or anxiety. If you’ve been brushed off before, you may think, ‘If I go to the doctor, they’re just going to tell me I’m anxious.’”

Pamboukian also says that women are at times more passive than men when describing symptoms to their doctors, asking questions, and requesting tests and screenings. “You really have to be your own advocate,” she urges. “If you’re concerned about your symptoms, if you feel that something isn’t right, you need to ask your doctor to do the screening tests.”

Sanderson says that mothers, in particular, must take the lead in promoting heart health. “Women, in my opinion, are the role models within their houses,” she says. “Most moms are the ones who cook, who do the grocery shopping, who arrange activities for the kids. Men are more involved with the children now than in generations past, but women are still often the major decision-makers. So they really have a huge responsibility, not only for their own health, but also for future generations.”

The Secret Syndrome

Obesity and poor nutrition will speed a woman toward a diagnosis that is not often mentioned but very often associated with heart disease: metabolic syndrome. “During the last few years, research has shown a clear association between metabolic syndrome and risk of heart disease, so our patients need to avoid being in that state,” says UAB cardiologist Salpy Pamboukian, M.D. She notes that “metabolic syndrome” isn’t a term that many physicians use with patients, although it’s estimated that more than 50 million Americans fit the grim profile:

  • established obesity, particularly excess fat around the abdomen;
  • insulin resistance, or glucose intolerance, in which the body is unable to properly use sugars in the bloodstream;
  • hypertension;
  • blood fat disorders—such as low HDL cholesterol and high triglycerides—that encourage the buildup of plaque in the arteries;
  • prothrombotic (blood-clot-promoting) states such as high fibrinogen or plasminogen activator inhibitor-1 levels in the blood; and
  • pro-inflammatory states such as elevated levels of C-reactive protein in the blood.

Although metabolic syndrome is frequently linked to type-2 diabetes, Pamboukian says that the two are not always intertwined. “Not all people with type-2 diabetes fit the criteria for metabolic syndrome,” she says, “but those who do are veritable powder kegs in terms of their susceptibility to cardiovascular disease.”

Doing What Works

By the time middle age sets in, decades of poor eating and lack of exercise weigh so heavily on many women that they’re simply tired and unmotivated to change. “When people have a certain lifestyle for a long time,” says Bittner, “they really have no recollection of what it’s like to feel good. We try to get the point across that if you exercise and lose weight, you’ll actually genuinely feel better.

“That should be the motivation. I don’t think we should be saying to people, ‘Exercise today to prevent a heart attack in 2025.’ The motivation should be, ‘If I sit around all day long, I’m going to feel terrible at the end of the day. So I’m going to get some exercise so that I’ll feel better.’ The problem is, people aren’t saying that to themselves—and maybe it’s because they just don’t remember what it’s like to feel good.”

“Maybe it’s that you think that exercising takes too long,” suggests Sanderson. “Or maybe you exercised today and you felt horrible so you’re not going to do it tomorrow. People don’t realize that it’s the everydayness of it—of eating right, exercising, not smoking—that provides the benefits. Pretty soon it just becomes a habit and you do feel so much better. But getting to that point is tough.”

A Hot Flash or a Heart Attack?

Your granddaughter has just learned to crawl, and boy does she keep her parents on their toes. You love to babysit her whenever you can, but sometimes you just don’t feel like yourself. You have heartburn and an upset stomach more often than you used to, and you can’t ever seem to get to a comfortable temperature. You don’t sleep well, and you’re more tired than you used to be. How do you know if it’s hormones, heart disease, or just a hectic day?

As women age, it often seems that hormones get all the attention. Between menopause and breast cancer—both of which are at their peak incidence in the age ranges of 50 to 65—issues such as high blood pressure and heart disease tend to take a back seat.

What effect do hormones—and hormone-replacement therapy—have on heart disease? “I think most people would say that there’s definitely a relationship between being either premenopausal or postmenopausal and the incidence of coronary disease,” says Pamboukian. “Estrogen seems to be protective; it’s associated with higher HDL [good] cholesterol and lower LDL [bad] cholesterol.”

But just replacing estrogen after menopause doesn’t appear to be the answer, she says. In the last four years, data released from the Women’s Health Initiative and the Heart Estrogen/Progestin Replacement Studies (HERS) have called into question the benefits of hormone-replacement therapy for postmenopausal women. “Right now hormone-replacement therapy is not indicated for prevention of heart disease,” says Pamboukian. “It is only indicated for women who are having severe symptoms of menopause.”

When trying to interpret all of the data, Bittner says it’s important to remember one thing: “You cannot disentangle age from menopause.” For that reason, she says, the exact relationship between hormones and the heart remains unclear.

How Low Must We Go?

Among the screenings women need to have beginning in their 30s—if not before—are their cholesterol levels. “Cholesterol-lowering medicines are pretty standard for someone who’s been diagnosed with coronary artery disease or who is at risk,” says Pamboukian. “Even if cholesterol is measured as normal, we’re still very aggressive about bringing it down to the newest goals. For patients with risk factors but no diagnosed heart disease, the revised LDL goal is less than 100. If you develop heart disease, the goal for LDL [bad] cholesterol used to be less than 100; now it’s less than 70. A lot of people probably aren’t meeting the new target because it’s a really aggressive target.”

And what about good cholesterol? “You want to try to get your HDL cholesterol levels as high as you can,” she says. “Medication can help raise it, but weight loss, quitting smoking, and exercise are really the best ways to raise your HDL.”

“Some people say that after menopause women have higher rates of heart disease than men. But that’s not true. If you look at absolute numbers of deaths, in the younger age groups, it’s four men to one woman. As women get older, the difference gets smaller and smaller. But even if you look at 80-year-olds, men still have a higher risk of dying from heart disease.

“What is true, if you look at absolute numbers of deaths, is that males die younger, so you’re left with a lot of older women. Many more older women die of heart disease than older men—but that’s because the men are already dead.”


Redefining the Disease

There’s always good news and bad news when it comes to heart disease and women. Women have a lower incidence of heart disease than men at any age—but women who develop heart disease often have a worse prognosis in terms of persistence of symptoms. As researchers get better at generating images of the body, they’re finding clues about why symptoms sometimes continue despite treatment.

While breast cancer gets a lot of press, it simply does not strike women with nearly the frequency of heart disease. So why do we hear so much more about “the C word”? “I think people don’t appreciate how bad heart disease can be,” says Pamboukian. “Maybe they don’t realize that when you develop heart disease, you have to live with it your whole life. With cancer, people know you have to take chemotherapy, and you get really sick. Not everybody realizes that heart disease is a chronic disease, and it can be very limiting, and you have to be on a lot of medicine all the time.”

Pamboukian notes that heart disease doesn’t have to obliterate a person’s lifestyle. “Some people have a heart attack, they take it as a warning sign, do the things they’re supposed to do to modify their lifestyle, take their medicine and follow their doctor’s advice regularly, go back to work and all their old activities, and have a fine life. But there are also people who become so debilitated that they can’t walk across the room, they’re on a bunch of medicines, and they have a very bad quality of life.” She says it often comes down to the patient: Those who address the disease early and aggressively will fare much better.

When a woman has chest pain, she’s likely to receive an angiogram, a test in which a cardiologist injects dye into her arteries to look for blockages. If a blockage is found, often the vessel is opened through angioplasty and placement of a stent. It’s becoming clear, however, that a blocked blood vessel is only one scenario for life-threatening heart disease.

“It’s so difficult to get a handle on heart disease because we use the same names for different types of things,” says Bittner. “Our current definition of coronary artery disease is that you get a blockage in a major coronary artery that feeds smaller blood vessels throughout the heart. We call that condition ‘stenosis.’ If it’s a complete blockage, then you have a heart attack. If it’s not a complete block but a critical blockage, you may find that you’re less able to tolerate exertion, so you get symptoms associated with heart disease because this area doesn’t get enough oxygen.

“The question is, should we define heart disease anatomically, as we have been doing, or do we define it physiologically—in terms of what happens to the tissue being fed by the blood vessel?” asks Bittner. “In other words, shouldn’t the question be, is the tissue oxygen-deprived—what we call ‘ischemic’—or not?”

Bittner says it’s important to distinguish between stenosis and ischemia, because the two don’t necessarily coincide. “It turns out that the vascular system is incredibly complicated—the extent of heart disease is not simply a matter of how much blockage is in one given segment,” she says.

Thanks to intravascular ultrasound, an improved way of imaging blood vessels, researchers are exploring a whole range of processes in the heart that decrease blood flow, and thus oxygen, to body tissue. And none of these conditions will show up on an angiogram:

  • Plaque buildup: Instead of having one blockage, a person could have plaque buildup throughout the artery wall, which could impede blood flow. “But if you shoot an angiogram,” says Bittner, “you wouldn’t see a blocked artery; you would see something that looks like a small normal blood vessel. And unless this 60-year-old patient happened to have a baseline angiogram when she was 20, you’re not going to know how big that blood vessel has been in the past.”
  • Abnormal function of vessels: Blood vessels are lined with a single layer of cells called the endothelium. These cells are metabolically active and allow the blood vessels to adapt to different demands and prevent the blood from clotting. “The body is designed so that when you are under physical stress, your blood vessels dilate to accommodate blood flow. When the endothelium has been injured, it could respond inappropriately, and instead of getting bigger, your blood vessels might get smaller with exercise or emotional stress.” Such blood-vessel spasms also cut off vital blood flow to heart tissue.
  • Microvascular disease: Clogging isn’t just for major arteries. Vessels that are too small to see on an angiogram can also become blocked or dysfunctional. And blockages in these small vessels, known as the microvasculature, can cause a lack of blood flow that will be evident during a stress test but never visible on an angiogram.
  • Collateral vessel dysfunction: “You don’t have just one blood vessel going out from your heart,” notes Bittner. “There are links between the different vascular areas in the heart. So one person might have 99 percent blockage in a coronary artery and still have perfectly good blood flow to her heart tissue because she has well-developed collaterals. But the next person might have 60 percent blockage in the same blood vessel and get symptoms during a stress test, because she doesn’t have good collaterals.”

Essentially, says Bittner, there are many different ways in which blood flow to the heart can be disrupted. “And in many of those cases, patients will have stress tests that show areas of poor blood flow, but then when they have angiograms, their blood vessels will look okay—so physicians assume the stress tests must have been false-positives.

“My gut feeling is that women and men have all of these disease processes, and maybe the relative importance of each one differs by gender. So maybe the reason women tend to have ‘atypical symptoms’ [see box on page 33] is that they’re not really atypical—maybe different types of disease processes simply have different symptoms. Maybe the outcomes between men and women differ because angioplasty will fix a blocked artery, but it won’t fix clogs in the microvasculature. All of this is further complicated by the fact that these disease processes are not mutually exclusive, so you could have a diffusely narrowed blood vessel and then a severe blockage on top of that.”

The Cardiac Rehab Program at UAB

Learning to prefer salads over Big Macs is hard. So is learning that walking around the neighborhood not only gets easier with time but also makes you feel better the next day. The cardiac rehab program at UAB, now in its 10th year, is designed to be the friend and counselor that helps people with heart disease succeed in making these crucial lifestyle changes. It helps patients change their habits in ways that make them permanent, while providing follow-up care and monitoring for those who’ve had heart attacks.

“From the patient’s perspective, all of this requires work. It’s not like lying on a table and having some discomfort for half an hour while you get angioplasty and then walking away feeling ‘cured,’” says Sanderson. “Patients have to make a commitment to go walking every day, to eat healthy, and to not smoke. They have to make a commitment to go to their doctors and to take their medicines regularly. And that’s hard work.”

But it’s worth it. “I think that as a society we have to put more emphasis on being accountable for the choices we make,” says Sanderson. “To enhance public health, we need to create an environment that’s more conducive to healthy lifestyles. When you go to your favorite steakhouse, you don’t see a two-for-one special for spinach salads; you’re offered twice the ribs for the same low price. Right now, society is designed to encourage you to eat more and do less.”

Vessels Great and Small

“So a woman comes in with chest pain,” says Bittner, “and you see the angiogram, and you go in and put this nice little stent where you find a blockage in her artery. And then the blood vessel looks absolutely gorgeous, and the blood flows through. But she’s still having chest pain.

“Well, it may be that the woman had chest pain in the first place not because she had this nasty blockage but because she had blockages in her smaller blood vessels. And all you’ve fixed with angioplasty is the big blood vessel, so she’s not going to be symptom-free.”

Currently, our entire treatment system is focused on fixing this one kind of blockage, says Bittner. “That is what angioplasty does; that is what bypass does,” she says. “But it seems likely that we are dealing with a mixture of diseases, and we don’t have a good handle on what the distributions of these different diseases are between genders. Even the medicines that we’re using are largely designed to treat blockages in the big blood vessels or to dilate the blood vessel. But if your blood vessels are behaving like lead pipes, are those medicines going to open them up? Maybe.”

Bittner is optimistic that as imaging techniques improve, researchers will find treatments that address the full range of coronary artery dysfunction. But for the hundreds of thousands of potential patients in the meantime? “Again, why are we looking for the magic bullet? Why are we completely focused on finding the serum marker, a female-specific stent, or special scanning just for women?” she asks. “All of these things are important from a research standpoint, but we should be doing just as much work to address the risk factors that we know about. We know that healthy eating is protective. Physical activity is protective. Normal blood pressure and cholesterol are protective. Why don’t we focus on the things we already know are good for us?

“We can talk and talk about care disparities and atypical symptoms and why women are not responding to treatment as well as men. But preventing the disease—and preventing the disease from progressing—still boils down to controlling the classic risk factors that we know will make a difference. Lifestyle changes and medications for hypertension and high cholesterol do work. We simply have to apply them to all women at risk.”

Atypical Symptoms

As they grow older, many women find that fatigue and an upset stomach are constant companions. So how do you know if these are normal signs of aging, hormonal changes, or potential signs of heart trouble?

Some symptoms of a heart attack are reported more commonly among women than among men. While chest pain is still the cardinal sign of an attack, any combination of the following could indicate an imminent heart attack:

  • shortness of breath
  • nausea and/or vomiting
  • severe sweating
  • pain in the jaw and/or arm
    abdominal pain
  • dizziness and/or fainting
  • difficulty when walking or during other physical exertion

UAB cardiologist Salpy Pamboukian says patients should seek prompt medical attention if symptoms are severe, especially if they are associated with difficulty in breathing, feeling faint, or actually fainting.