Micro-vascular Angina: a Puzzling Form of Chest Pain and Unrecognized Danger

It's more common in women than men and often goes untreated

by Vinita Subramanya, M.B.B.S, M.P.H. and Erin Michos, M.D., M.H.S.

A type of cardiovascular disease known to physicians as micro-vascular angina affects the heart's tiniest arteries and causes chest pain. The disease is sneaky, in that it doesn't show up on traditional heart scans but is linked to serious health outcomes, like heart attacks. 

Here is what you need to know about micro-vascular angina, which is often unrecognized and under-treated and more common in women than men.

What Is Micro-vascular Angina?

When the oxygen supply to the heart muscle tissue cannot meet the heart's metabolic demand, it can sometimes (but not always) cause chest pain, known as angina. The more common form of angina is from blockages in the heart's arteries due to buildup of cholesterol plaque a condition called obstructive coronary artery disease that limits blood flow to the heart.

Physicians frequently evaluate people with chest pain by stress testing and sometimes with an angiogram a type of X-ray in which dye is injected into the heart's arteries to see blockages or narrowing. This test can help determine what type of treatment is needed.

But many individuals with angina don't show obstructions or blockages in their heart arteries when evaluated by an angiogram. This problem of chest pain without obstructive coronary artery disease or micro-vascular angina may be caused by problems with the small arteries of the heart instead of the large ones visualized in the traditional scans.

Mechanisms that contribute to micro-vascular angina aren't fully understood, but some potential causes have been identified. It can be due to temporary spasms of the larger heart arteries or from abnormal functioning of the endothelial cells that line the heart arteries.

Endothelial cells release chemicals that relax and contract the small arteries. This chemical release can become imbalanced in a diseased heart. Risk factors such as smoking, diabetes and inflammation can often cause these endothelial cells to malfunction. Patients with micro-vascular angina may also have an increased sensitivity to pain due to certain substances released from these cells.

What Are the Signs and Symptoms?

Micro-vascular angina, formerly known as cardiac syndrome X causes a constellation of symptoms and signs that include chest pain during physical exertion, signs of reduced blood supply to the heart as determined by stress testing or advanced cardiac imaging, and normal-appearing arteries on an angiography of the heart.

Micro-vascular angina diagnosis is often missed because it can show up in a more unusual fashion than chest pain from obstructive coronary disease. For example, micro-vascular angina episodes can occur during times of mental and emotional stress or even at rest, rather than just physical exertion; episodes can last longer than those from obstructive coronary disease, and they respond less well to standard therapies, like nitroglycerin.

Micro-vascular angina symptoms can sometimes be falsely blamed on other causes, like stress and anxiety, panic attacks or gastrointestinal troubles. For many years during chest pain assessments, physicians only looked for signs of obstructive coronary artery disease, and they dismissed chest pain if they found no obstruction. This led to missed opportunities for implementing the appropriate treatments for this condition.

Both men and women can develop micro-vascular angina, but it's much more common in women. Among patients with stable chest pain about 41 percent of women versus 8 percent of men show no large artery obstructions on angiograms.

Why Is Micro-vascular Angina Serious?

While micro-vascular angina is usually a stable condition, women are twice as likely as men to have normal-looking heart arteries (without apparent blockages) when they actually have a heart attack. This unusual type of heart attack is called myocardial infarction with non-obstructed coronary arteries, or MINOCA.

Spasms in the blood vessels can be one potential cause. In many instances, a special type of heart ultrasound can confirm plaque in the heart arteries that had eroded or ulcerated. These heart arteries aren't 'normal' despite the absence of blockages.

The Women's Ischemia Syndrome Evaluation, sponsored by the National Heart, Lung, and Blood Institute, was a landmark study that began back in 1996 and enrolled over 900 women with signs and symptoms of heart disease who underwent a coronary angiogram.

The outcomes of these women followed for more than a decade have contributed much of the knowledge that we know today about micro-vascular angina, including some of the mechanisms behind this puzzling condition and its long-term risks. 

For example, the WISE study found that the heart's arteries react with abnormal patterns of narrowing and relaxing in women with micro-vascular angina. More importantly, the WISE study concluded that even without evidence of major heart artery obstructions, micro-vascular angina is worrisome.

Patients with angina but without obstructed arteries still have increased rates of heart attacks, strokes, heart failure and death compared to women without angina. This is magnified among women with more cardiovascular risk factors. Micro-vascular angina increases death rates by 1.5-fold. People with angina also have higher hospital readmission rates for chest pain and repeat coronary angiographies.

The WISE study led to great improvements in diagnosing and treating micro-vascular angina, but gender differences still exist in the clinical outcomes, with women still being under-diagnosed and under-treated.

How Do We Test for Micro-vascular Angina?

Since we can't determine the causes of chest pain solely from the symptoms, we look to additional ways of diagnosing angina. Physicians classify symptomatic women by their risk as either low, intermediate or high, and evaluate them based on cardiovascular risk factors.

Low-risk women don't usually need further testing. Low to intermediate and intermediate-risk women should be further evaluated using an exercise treadmill test that measures a woman's exercise capacity and an electrocardiogram that measures electrical activity of the heart.

Intermediate to high-risk women with an abnormal ECG will need further imaging using any of the following techniques: myocardial perfusion imaging (or nuclear stress testing), stress echocardiography and cardiac MRI or cardiac CT-angiography.

High-risk women may be given a traditional coronary angiogram which may even be paired with an invasive test considered a gold standard the coronary flow reserve measurement. The coronary flow reserve test measures how much the heart arteries can dilate and increase blood flow above the normal volume when given a specific drug that relaxes the arteries. Revealing the exact cause of the micro-vascular dysfunction requires more in-depth testing.

How Do We Treat Micro-vascular Angina?

An important step to improve outcomes among women with micro-vascular angina is to recognize that they are at risk for some of the same outcomes as people with obstructive coronary disease. Physicians' treatment goals include a combination of strategies aimed to both increase blood flow and reduce workload in the heart.

While there aren't set regimens to treat micro-vascular angina, two therapeutic mainstays use medications that aim to improve chest pain and prevent plaque buildup in the arteries. Responses to treatments aren't consistent among men and women and may be related to the differences in the disease mechanisms. Anti-angina medications are used to improve symptoms of chest pain. 

These include beta blockers that improve the heart's blood flow by reducing its workload, calcium channel blockers that improve the blood flow and decrease blood pressure (thereby further reducing the workload) and nitroglycerin that works to improve blood flow. 

Aspirin prevents clot formation and decreases inflammation. Other newer drugs act on the heart's cellular processes and improve their functioning during temporary periods of low blood flow.

Other medications to treat micro-vascular angina include statins that lower cholesterol levels and prevent cholesterol from building up in the arteries, and the angiotensin converting enzyme inhibitors that improve the function of the endothelial cells lining the heart's arteries. 

Newer therapies under investigation include the class of drugs known as phosphodiesterase inhibitors that act at the cellular level and transcutaneous electrical nerve stimulation, both of which improve arterial blood flow.

How Do We Prevent Micro-vascular Angina?

The well-established (and largely preventable) risk factors that contribute to obstructive coronary disease such as high blood pressure, high cholesterol, diabetes, smoking and sedentary lifestyle are just as important for developing micro-vascular angina. 

Autoimmune conditions like rheumatoid arthritis and lupus may also raise the risk of developing micro-vascular angina. And young women with lower than normal levels of estrogen are at risk. 

Prevention strategies include reducing one's risk through appropriate medical and lifestyle changes, like controlling high blood pressure, cholesterol and blood sugar levels. Improvements in diet and physical activity levels can go a long way in reducing micro-vascular angina frequency.

People should eat a diet rich in omega-3 fatty acids, fruits, vegetables and whole grains, and minimize processed foods and foods with higher saturated fat, sodium and refined sugars. 

It's important to maintain a healthy weight and better manage stress levels through physical activity, stress management, relaxation programs, and meditation. Quitting smoking also should be a top priority.

Take-Home Points:

1) Micro-vascular angina is a form of chest pain due to abnormalities in the tiny arteries of the heart that cause decreased blood flow.

2) Since micro-vascular angina occurs in the absence of blockages or obstructions in the large heart arteries, it is often under-recognized and under-treated.

3) If you have chest pain after exerting yourself and get an abnormal result on a stress test but have no evidence of blockages on an angiogram, it is likely you have micro-vascular angina.

4) Women have this condition more often than men, and their symptoms can be different from men's symptoms.

5) People with micro-vascular angina have an increased risk of heart attacks and death in the next five years compared to patients without angina symptoms.

6) Controlling risk factors, such as not smoking, as well as managing blood pressure, blood sugar and cholesterol and other blood fats, are important for preventing and controlling symptoms of this disease.

7) Eating a healthy diet and getting plenty of physical activity are also very important for preventing and treating micro-vascular angina