Coronary Microvascular Dysfunction

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Topics: Heart Disease & Prevention Women's Health Transcript: Coronary Microvascular Disease (transcript)

Research supports that not only do men and women present with heart disease differently, they can also develop it differently. Coronary Microvascular Disease is predominantly a women's heart disease - one that is often overlooked and under-diagnosed. Is it possible to have heart disease and yet appear to have healthy coronary arteries? The surprising answer is a resounding "yes." What is Coronary Microvascular Disease? Up until about a decade ago, patients with cardiovascular disease symptoms, but with no evidence of blockages in their larger coronary arteries, posed a medical mystery for doctors.

Thanks to advances in diagnostic tools, researchers discovered the problem with these patients occurred not because of coronary artery disease (CAD) in the larger coronary arteries, but rather in the smaller coronary arteries. Thus the term "coronary microvascular disease" was born. Your body needs a flow of oxygen-rich blood to nourish it and your heart muscle is no exception. When the heart doesn't get enough oxygen to meet its needs (myocardial ischemia) one of two things can happen. If the deprivation is limited, chest pain or pressure called angina may occur. If the flow of blood is cut off, the result is a heart attack (myocardial infarction or heart muscle death).

Blood flows to the heart muscle first through three large coronary arteries, then through branches of thousands of smaller arteries called arterioles. Healthy arteries are hollow tubes and the inner lining is smooth and elastic, allowing blood to flow freely. When you exercise, a healthy artery can stretch to let more blood flow to your body's tissues. The transition from artery to arteriole is a gradual one, marked by a progressive thinning of the vessel wall and a decrease in the size of the passageway.

The job of the larger arteries is the distribution of blood. They range from 1.0 - 4.0 millimeters in size. The job of the arterioles is both blood distribution and resistance (pressure and flow regulation). Think of the arterioles as "taps" for circulation, turning the flow up or down to match the needs of your body. They range from 0.1 to 0.5 millimeters in size.

Symptoms of Coronary Microvascular Disease
The symptoms of heart disease, in both men and women, often result from traditional coronary artery disease (CAD). With coronary artery disease, the trouble begins when the inner walls of the larger coronary arteries are damaged from issues such as high blood pressure, high cholesterol, smoking and diabetes. When this happens, plaque (a substance made up of excess cholesterol, calcium, and other substances in the blood) starts to build up (atherosclerosis).

Plaque can slow and completely block the flow of blood to the heart muscle. It can also crack, causing blood cells called platelets to clump together and form blood clots. This type of heart disease can be seen with tests such as coronary angiograms and with noninvasive tests such as special CT and MRI scans.

Coronary microvascular disease is an elusive disease. It doesn't show up on many standard tests. When a doctor sees an angiogram with wide open arteries, he or she may assume that symptoms like chest pain, shortness of breath, light-headedness, diffuse discomfort in the chest or unusual exhaustion are caused by something other than heart disease. If the doctor isn't familiar with coronary microvascular disease, it's unlikely that additional tests will be ordered. Even if the large coronary arteries are clear, coronary microvascular disease can still be present. The angiograms of 50% to 60% of women and 20% of men with symptoms of heart disease show clear arteries on an angiogram.

Medical experts believe that the majority of those have coronary microvascular, a disease that's just as dangerous as coronary artery disease. Just like coronary artery disease, it increases the risk of heart attacks and heart failure.

The characteristics of microvascular dysfunction include: A build-up of plaque that spreads evenly throughout the walls of the small arteries. So while there may be no obvious blockages, blood flow to the heart is still low. (Coronary microvascular is also called non-obstructive CAD.) Vessels that don't expand or dilate properly during physical or emotional stress. Vessels that spasm (contract) abnormally. Coronary microvascular disease has some other unique features. Symptoms of angina with coronary microvascular disease may or may not be the typical chest pain seen in coronary artery disease.

Plus, coronary artery disease symptoms often first appear while a person is being physically active, for example while jogging or going up stairs, and coronary microvascular disease signs are often first noticed during routine daily activities and during times of mental stress. Diagnosing Coronary Microvascular Disease Doctors are refining their methods for diagnosing coronary microvascular disease and research is ongoing to find the best preventive strategies and treatments. In the meantime, doctors are following similar approaches to those used to prevent and treat coronary artery disease. Diagnosis remains the biggest hurdle for people with coronary microvascular disease.

Many people spend years going undiagnosed and some never are. If you have recurrent chest pain and your doctor says you're fine because you have clear coronary arteries, don't give up. Sometimes doctors get it wrong. Seek a second opinion and if that doesn't help, seek a third. You're the expert on your own body. When it's trying to tell you something, listen. Most importantly, if you think you're having a heart attack call 9–1–1. Acting fast at the first sign of heart attack symptoms can save your life and limit damage to your heart.
Treatment is most effective when started within 1 hour of the beginning of symptoms.

Quick Facts
• Coronary microvascular disease (MVD) affects the heart's smallest coronary arteries, called arterioles.
• Coronary microvascular disease is more common in women than in men.
• Heart disease, in general, is a different disease for women than it is for men.
• Signs and symptoms of coronary microvascular disease often differ from those of traditional coronary artery disease (CAD).

Typical signs and symptoms of cornary artery disease include angina (chest pain), feeling pressure or squeezing in the chest, shortness of breath, excessive sweating, and arm or shoulder pain.
Women with coronary microvascular disease may also have shortness of breath, sleep problems, fatigue (tiredness), and lack of energy.
Symptoms are often first noticed during routine daily activities and times of mental stress.

• Coronary microvascular disease occurs when plaque forms in the arteries, when the arteries spasm (tighten), or when the walls of the arteries are diseased or damaged, preventing enough oxygen-rich blood from getting to the heart muscle.
• In coronary microvascular disease, plaque doesn't always lead to blockages as it does in traditional coronary artery disease (CAD). For this reason, coronary microvascular disease is called non-obstructive coronary artery disease.
• Women with chest pain and other heart symptoms are more likely than men to have clear coronary arteries when diagnostic tests are performed.
• The same cluster of risk factors that cause coronary artery disease may cause coronary microvascular disease. These include unhealthy cholesterol levels, high blood pressure, smoking, insulin resistance, diabetes, overweight and obesity, lack of physical activity, age, and family history of early heart disease.
• Coronary microvascular disease is difficult to diagnose.

Your doctor may start with a questionnaire called the Duke Activity Status Index, which measures how well you're able to do your daily activities.
Other tests include pharmacological stress testing and a special type of coronary angiogram used to measure coronary artery flow reserve.

• If you have coronary microvascular disease, you can take steps to stop it from getting worse. These may include lifestyle changes, medicines, and regular medical care. Ask Your Doctor This list of questions is a good starting point for discussion with your doctor; however, it is not a comprehensive list.
What is my risk for heart disease?
What is my blood pressure, and is it at a healthy level?
What is my blood cholesterol, and is it at a healthy level?
What lifestyle changes (such as diet, exercise, etc.) should I make to prevent heart disease?
Do I need screening tests, even though I don't have heart disease symptoms? What sorts of symptoms should I be watching for? I've noticed these symptoms: . . .
What medical tests should I take to get an accurate diagnosis?
Are the diagnostic tests that are most effective in detecting coronary MVD available locally?
I've heard heart disease is different for women than for men.

What are the differences? What are the differences in how you diagnose and treat coronary MVD versus coronary artery disease (CAD)?

How familiar are you with coronary microvascular disease?
Have you treated other patients with the condition?
Should I be referred to a specialist? If your doctor finds evidence of heart disease: How serious is my condition?
What are the treatment options, and what are their benefits, risks, and side effects?
Am I a candidate for a heart attack, even after taking medication?
When should I suspect that I am having a heart attack?
Should I get involved in a clinical trial? Key Point 1 When it comes to heart disease, not only are the symptoms sometimes different for men and women – but the disease itself may be different.

There's an entertaining theory that men and women are from different planets. It's a not-so entertaining fact that men and women experience heart disease differently. It's not always clear why, but women are less likely to survive a heart attack than men.
Women have a 50 percent greater chance of dying during heart surgery. And, they're more likely than their male counterparts to develop heart failure, a weakening of the heart muscle that can be incapacitating and ultimately fatal.
Heart disease kills 500,000 women every year – ten times more than breast cancer and more than all other cancers combined. It's also a leading cause of disability. Eight million women are currently living with it.
While women develop cardiovascular disease about ten years later than men, it's estimated that one in ten American women 45 to 64 years of age has some form of heart disease, increasing to one in four women over the age of 65.

Historically, studies that set the standard for detection and treatment of heart disease were mostly done on men. But researchers found the results didn't always apply to women. Now, thanks to new research sponsored by National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI), more attention is being directed toward a better understanding of the unique features of heart disease in women.
Here's what scientists are finding out about gender differences and heart disease. Women with heart disease may have different symptoms than men. Women may experience the classic symptoms of gripping chest pain, sweating and shortness of breath, but they also may present with vaguer symptoms like generalized discomfort in the chest, breast, back, shoulders, jaw, neck or throat; indigestion; nausea; light-headedness; palpitations; sleep disturbances; and unexplained fatigue.

Tests that reliably pick up signs of heart damage in men don't always work in women. These range from simple blood tests to exercise stress tests to standard angiograms.
Some women don't have the strength to do a full exercise stress test and an incomplete one doesn't work the heart enough to yield truly useful results.
Single-vessel heart disease, which is more common in women than in men, may not be picked up on a routine exercise stress test.
Women with chest pain and other heart symptoms are more likely than men to have coronary microvascular disease even though tests show clear large coronary arteries.
(See More About Women and Coronary MVD below.)

Women tend to have heart attacks later in life. As a result, they're more likely to have other health issues. Symptoms of heart disease might be attributed to existing conditions such as arthritis or diabetes. Problems like high blood pressure, high cholesterol and diabetes may make surgery a riskier proposition for them. Women have smaller hearts and arteries than men.
One reason women haven't fared as well as men after bypass surgery and balloon procedures may be that their smaller vessels clog up again more easily after the procedures. In addition, surgeons performing bypasses in women are less likely to use an artery from inside the chest wall, because it's smaller and harder to work with, even though using the chest artery gives most patients better odds of long-term survival.

There may be fundamental differences in the way women's hearts work. Researchers believe that women have a different intrinsic rhythm to the pacemaker of their hearts, causing them to beat faster. They also hypothesize that it may take a woman's heart longer to relax after each beat. Several recent landmark studies have revealed that more women than men suffer from coronary microvascular disease. It's estimated that of the 8 million women in the U.S. with heart disease, as many as 3 million of them have coronary microvascular disease.
The diagnosis of coronary microvascular disease poses a unique challenge. Chest pain and other symptoms that the heart muscle isn't getting enough blood have traditionally signaled a narrowing or blockage in one or more of the heart's large arteries – a condition that's easily seen on an angiogram. But, in about 50% to 60% of symptomatic women and 20% of men, the problem lies not in the major arteries but in the smaller branches which are virtually invisible on a standard coronary angiogram.

Bottom line, coronary microvascular disease, like traditional coronary artery disease (CAD), increases a woman's chance for a heart attack. Researchers are just beginning to understand coronary microvascular disease. The same risk factors that cause problems with the larger coronary arteries – heredity, age, race, blood pressure, blood cholesterol, obesity and smoking – may also contribute to coronary microvascular disease. Women appear to be more affected by certain factors, such as high blood pressure, smoking and diabetes than men. In addition, there are a host of other risk factors unique to women.

Only women become pregnant, experience menopause and are prescribed contraceptive pills and postmenopausal estrogens. Theories on why the disease may differ in women include the following:
• Low levels of estrogen. Because estrogen plays a role in processing nitric oxide, which helps arteries function properly, the endothelium may suffer when natural estrogen levels wane.
• More inflammation (an overreaction by the immune system). Inflammation stimulates the body to use cholesterol in the bloodstream as a band-aid to cover up irritated areas in the blood vessels.
• Higher incidence of anemia. Anemia is thought to slow the growth of cells needed to repair damaged blood vessels.
• Lower levels of hemoglobin (a protein in red blood cells that carries oxygen). Hemoglobin deficits may starve the heart muscle and also reduce nitric oxide levels.
• Lower HDL ("good" cholesterol) levels. There is evidence that having low HDL is more predictive of the development of coronary heart disease in women than high LDL ("bad" cholesterol) levels are.

Findings so far have raised as many questions as have been answered, but the work represents a good start in zeroing in on ways to tailor diagnosis specifically for women. Progress has already been made in educating doctors about symptoms that, in the past, were under-recognized or misinterpreted in women.

Scientists are now focusing on how diagnostic and treatment techniques may need to be changed to improve women's outcomes.

Key Point 2
Coronary microvascular disease is tough to diagnose.

If you are experiencing symptoms that concern you, don't ignore them. You need to continue a dialog with your doctor until you're both satisfied. If your doctor suspects you are at risk for heart disease, there are a number of traditional diagnostic tests used to look for blockages that affect blood flow in the large coronary arteries (coronary artery disease or CAD).

However, standard tests for cornary artery disease, such as electrocardiograms, exercise stress tests, echocardiograms and angiograms don't always detect coronary microvascular disease (MVD), a disease where the smallest coronary arteries are affected.

For more information about tests to diagnose heart disease, see the Second Opinion episode on Cardiac Breakthroughs
As more is learned about coronary microvascular disease, new protocols and tests are emerging. Since symptoms of coronary microvascular disease often first appear during routine daily tasks, a questionnaire called the Duke Activity Status Index (DASI) that asks about an individual's ability to perform certain daily tasks can prove useful.
It yields information about how well blood is flowing through coronary arteries and also helps doctors select appropriate next steps.

Duke Activity Status Index Activity Points Can you take care of yourself (eating, dressing, bathing, etc.)?
0.8 Can you walk around your house?
0.5 Can you walk a block or two on level ground?
0.8 Can you climb a flight of stairs or walk up a hill?
1.6 Can you run a short distance?
2.3 Can you do light work around the house (washing dishes, etc.)?
0.8 Can you do moderate work around the house (sweeping, carrying groceries, etc.)?
1.0 Can you do heavy work around the house (scrubbing floors, moving heavy furniture, etc.)?
2.3 Can you do yard work (raking leaves, pushing a mower, etc.)?
1.3 Can you have sexual relations?
1.5 Can you participate in moderate recreational activities (golf, dancing, etc.)?
1.7 Can you participate in strenuous sports (swimming, singles tennis, skiing, etc.)?
2.1 Circle the points for a question only if you can answer "Yes, with no difficulty."
Add up the circled points. The lower the score, the greater the risk.
Total scores of 4.7 or below are considered higher risk.

Stress Tests
Stress tests are performed to determine whether there's enough blood flow to the heart during physical activity. They involve performing simple exercise, usually with a treadmill or a stationary bike. Sometimes pharmacological agents are used to simulate the heart's reactions to exercise. Standard stress tests tend not to be as reliable in women as in men, but using imaging such as echocardiograms or nuclear scans in conjunction with an exercise stress tests improves their accuracy.

• Adensosine Coronary Flow Reserve and Acetylcholine Endothelial Function Test with Cardiac Magnetic Resonance Imaging (MRI)

This is a pharmacological stress test. During the two-step test, the drug adenosine, which causes the small vessels of the heart to dilate, is injected into one of the coronary arteries and the amount of blood flow is measured. Next, the drug acetylcholine, which causes dilation in the large arteries, is injected and the amount of blood flow is again measured. The superior resolution of magnetic resonance imaging is used to get images of the beating heart and to look at its structure and function. MRIs can show poor blood supply to the innermost areas of the heart and can detect changes in the small coronary blood vessels. If either test shows decreased blood flow to the heart muscle, a diagnosis of microvascular disease can be made.

• Dipyridamole Positron Emission Tomography (PET) This cardiac PET scan also shows how much blood flow the heart receives at rest and under stress. During the first stage, fluorodeoxyglucose (FDG) is administered while the patient is at rest. The images that are produced from this first PET scan are checked with a second PET scan after the patient is administered dipyridamole, a drug that produces an effect in the body similar to the effects of strenuous exercise. Doppler Wire Coronary Angiogram The most definitive test for microvascular disease is a special type of coronary angiogram used to measure coronary artery flow reserve or coronary reactivity. It involves threading an ultrathin wire with blood-flow sensors at the tip deep into a coronary artery (called cardiac catheterization).

Blood flow in the artery is then measured before and after injections of one or more medications to cause the microvessels to dilate. The smaller the change in pressure and flow, the stiffer the vessels. This test is done only at a small number of cardiac centers in the country. Cardiac catheterization procedures are invasive and expensive, but the risks of doing them have to be weighed against the risks of not being accurately diagnosed. A great deal remains to be learned about coronary MVD, especially in women. In the meantime, there are some basic strategies that you can use to get an accurate diagnosis and the best possible medical care.
Listen to your body and believe in your instincts. If you feel strongly that something is wrong but your doctor can't find a problem, get a second opinion.
Find a specialist who is familiar with coronary MVD.
Ask questions. If you don't fully understand the answers, ask more questions until you do. There's nothing more important than your health.
By balancing assertiveness with respect for your physicians, you can get the information you need.

Key Point 3
If you've been diagnosed with coronary microvascular disease, getting adequate blood flow to your heart is critical.

Lifestyle changes are the most effective treatment. Treatment goals for coronary microvascular disease are three-fold – stop it from getting worse, improve quality of life by relieving symptoms, and prevent a heart attack. Standard invasive treatments for coronary heart disease (CAD), such as angioplasty, stenting and bypass surgery, aren't used to treat coronary microvascular disease. Instead, treatment focuses on reducing risk through managing underlying conditions. Talk to your doctor about your risk factors for heart disease and how to control them. Know your numbers-ask your doctor for these three tests and have the results explained to you. Lipid profile.

This test measures total cholesterol, LDL cholesterol (often called bad cholesterol), HDL cholesterol (often called good cholesterol), and triglycerides (another form of fat in the blood).

Blood pressure. Fasting blood glucose. This test is for diabetes. Know your body mass index (BMI) and waist circumference.

BMI is an estimate of body fat that's calculated from your height and weight. You can use the National Heart, Lung, and Blood Institute'sonline BMI calculator to figure out your BMI.

To measure your waistline, stand and place a tape measure around your middle, just above your hipbones. Measure your waist just after you breathe out. Know your symptoms and how and when to seek medical help.

Be able to describe the usual pattern of your symptoms. Know how to control them.
Know which medicines you take and when and how to take them. K
now the limits of your physical activity. Make heart-healthy lifestyle changes to reduce your risk factors.
You can't control some risk factors of heart disease such as age and family history. However, you can take aggressive steps to lower or control other risk factors such as high blood pressure, overweight and obesity, high blood cholesterol, diabetes and smoking.
Follow a heart healthy eating plan. Two heart healthy eating plans are the Dietary

Approaches to Stop Hypertension (DASH) diet (for people who have high blood pressure) and the Therapeutic Lifestyle Changes (TLC) diet (for people who have high blood cholesterol). Increase your physical activity.
Aim for at least 30 minutes of moderate-intensity activity on most, and preferably, all days of the week.
If you're trying to manage your weight and keep from gaining weight, try to get 60 minutes of moderate-to-vigorous-intensity physical activity on most days of the week.
Quit smoking, if you smoke.
Lose weight, if you're overweight.
Learn ways to avoid or cope with stress Take medicines as your doctor prescribes.
Standard anti-angina drugs that work by relaxing blood vessels, such as nitroglycerin, can help ease symptoms.
Nitroglycerin is prescribed to relax blood vessels, improve blood flow to the heart muscle, and treat chest pain.

High cholesterol and high blood pressure are almost certainly among the causes of microvascular disease. In addition to diet and exercise, lipid-lowering drugs like statins can be used to improve cholesterol levels and beta blockers, calcium-channel blockers or vasodilators to lower blood pressure and decrease the heart's workload.

If you have diabetes, check your blood sugar level every day to make sure your medicines and diet and exercise are working to keep it in a normal range. Two out of three people with diabetes die from heart disease and stroke.

Low-dose aspirin can be used to help prevent blood clots or control inflammation. Other blood clot reducers include anticoagulants and antiplatelets.

Treat anemia. It slows repair of damaged blood vessels. Anemia treatment depends on the cause and can involve iron supplements, folic acid or hormone injections, and blood transfusion, or antiplatelet drugs.

Although a great deal of new knowledge about coronary MVD has been uncovered in the last decade, more work needs to be done. Watch for new findings from the federally funded Women's Ischemia Syndrome Evaluation (WISE) study Medline Plus Conduct an off-site search for Coronary Microvascular Disease information from MedlinePlus

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