Cardiac Syndrome X

What is Syndrome X?

Syndrome X describes chest pain ( angina) in people who do not show signs of blockages in the arteries of their heart ( coronary arteries) after an angiogram, or X-ray of these arteries. It is not clear what causes Syndrome X, but there are several theories. Syndrome X patients do not seem to have a higher risk of dying early or having a heart attack, but they often continue to suffer from chest pain even after treatment.

Syndrome X is more common in women than men: about 70% of patients are women who are approaching or have already gone through menopause. In the WISE study of 936 women undergoing cardiac catheterization for chest pain, 60% did not have a major blockages in the arteries of their heart. Some of the women in this study may have had chest pain that was not heart-related.

How does Syndrome X differ from other types of chest pain?

Syndrome X is different from stable angina because an angiogram from a stable angina patient will show major blockages or narrowing in the coronary arteries. People with stable angina also typically experience chest pain during exertion that is alleviated with rest. The chest pain associated with Syndrome X is less predictable and can occur during exercise or at rest. Syndrome X patients may experience chest pain more often, more intensely, and for longer periods than people with stable angina. In addition, a medication called nitroglycerin usually relieves chest pain in stable angina patients, but often does not work in people with Syndrome X.

Strictly speaking, Syndrome X is a type of unstable angina because the pain may occur at rest; however, people are usually diagnosed with unstable angina as opposed to Syndrome X when they have major narrowing or blockages in the arteries of the heart, putting them at increased risk of having a heart attack or dying from heart disease.

You should not confuse Syndrome X with the metabolic syndrome, which used to be called Metabolic Syndrome X. The metabolic syndrome refers to a grouping of certain heart disease risk factors (including a large waistline and higher than normal blood sugar or blood pressure) in one person.

What causes Syndrome X?

No one knows exactly what causes Syndrome X and it is unlikely to have a single cause. Two factors that may be involved are lack of blood flow caused by microvascular dysfunctionand enhanced pain perception.

The term “microvascular” refers to very small blood vessels and, in this case, very small arteries of the heart. The major arteries of the heart are spaghetti-thin, but these tiny arteries are smaller still. When these tiny blood vessels narrow, oxygen cannot reach some areas of the heart muscle, which can cause chest pain. Restricted blood flow to the heart is called myocardial ischemia; myocardial refers to the heart muscle and ischemia is a combination of the Greek words for “restrain” and “blood.” About 50% of women with Syndrome X have evidence of microvascular dysfunction, but only about 20% to 25% show signs of restricted blood flow to the heart, suggesting that there are other factors involved. Syndrome X patients generally have good survival rates whereas people with true myocardial ischemia are at increased risk of having a heart attack or dying from heart disease.

Studies have also shown that people with Syndrome X have enhanced pain perception, meaning they feel chest pain more intensely than the average person. It is not known whether Syndrome X patients feel all types of pain more intensely or only chest pain.

Why are women more likely than men to have Syndrome X?

It is not completely clear why women are more likely than men to suffer from Syndrome X; however, hormones and other risk factors unique to women may play a role.

Women’s blood vessels are exposed to changing levels of estrogen throughout their lives, first during regular menstrual cycles and later during and after menopause as estrogen levels decline with age. Estrogen affects how blood vessels narrow and widen and how they respond to injury, so changes in estrogen levels mean changes in the behavior of the blood vessels. Women’s vessels may be “programmed” for more changes than men’s vessels, which could increase the risk of having problems in the lining of the arteries ( endothelium) and the smooth muscles in the walls of the arteries. Many women in the WISE study had evidence of damage to the smooth muscle in the small arteries. In addition to changing hormone levels, there are several other risk conditions for blood vessel problems that are unique to women, such as preeclampsia (a problem caused by high blood pressure during pregnancy) and delivering a low-birthweight baby.

Cardiac Syndrome X – Diagnosis, Treatment, Prognosis

How is Syndrome X diagnosed?

There are several steps for diagnosing Syndrome X. First, you must have a positive exercise ECG (usually a treadmill test), meaning the test showed that your heart was not getting enough blood during exertion. The second step is to have an angiogram, which is an X-ray of the arteries of your heart, to see if any of the major arteries are blocked. If there are no major blockages or narrowings in the blood vessels of your heart and other causes of chest pain are ruled out (including heart valve disease, muscle problems, or throat problems), then you will probably be diagnosed with Syndrome X. An angiogram cannot detect problems in the tiny arteries of the heart involved in microvascular dysfunction. In some cases, your doctor may recommend tests to see if blood vessel problems (vascular dysfunction) are responsible for your chest pain and to rule out coronary artery spasm (Prinzmetal’s Angina).

Can Syndrome X be cured?

Most people with Syndrome X do not have an increased risk of having a heart attack or dying from heart disease. However, they often must undergo repeated hospital visits and tests for chest pain, so treatment generally focuses on relieving this chest pain.

What are the first drugs used to treat Syndrome X?

Various medications are usually given to patients with Syndrome X, often with mixed results. Nitrates are usually given first; they relax the muscles of the heart and blood vessels, lowering blood pressure and improving blood flow and oxygen supply to the heart. Unfortunately, one study showed that less than half of all Syndrome X patients experience relief from chest pain after taking nitrates.

What are the next drugs used to treat Syndrome X?

Blood pressure drugs, including calcium channel blockers and beta blockers, may be tried next if nitrates don’t work. Calcium channel blockers work by relaxing the muscle cells lining the artery, which in turn improves blood flow to the heart and lowers blood pressure. Studies have shown that calcium channel blockers reduce episodes of chest pain in about one third of people with Syndrome X. Beta blockers lower the heart rate and allow more blood to flow to the heart. Beta blockers are effective in relieving chest pain in up to two thirds of Syndrome X patients, although responses vary.

What other drugs may be used to treat Syndrome X?

Since one of the possible causes of Syndrome X is enhanced pain perception, an antidepressant called imipramine(Tofranil) has also been used to treat this condition. In one small study of 18 female Syndrome X patients, imipramine reduced the frequency of chest pain episodes compared to placebo. However, most patients (83%) experienced side effects, and in 3 people the side effects were so severe that they had to stop taking the drug. Overall, taking the drug did not improve quality of life compared to placebo.

Women tend to develop Syndrome X around menopause when estrogen levels decline, so hormone therapy has also been studied. In a study of 25 women, estrogen patches reduced chest pain episodes from an average of 7 per 10 days to fewer than 4 over 8 weeks. However, large trials have found that hormone therapy increases the risk of heart attack and blood clots. No large studies on hormone therapy involved women with Syndrome X, and it is not known whether the benefits of chest pain relief outweigh the increased risk of heart and blood clotting problems.

Can Syndrome X be prevented?

Since it is not known exactly what causes Syndrome X, there is very little information on how to prevent it. However, it is always a good idea to maintain a heart healthy-lifestyle that includes:

  • Quitting smoking
  • Having healthy cholesterol levels
  • Lowering high blood pressure
  • Being physically active
  • Eating a heart-healthy diet

What is the prognosis for patients with Syndrome X?

Most older studies found that men and women with Syndrome X are not at increased risk of dying early or having a heart attack. However, more recent findings indicate that Syndrome X may not be as harmless as was once thought, particularly in patients who test positive for problems in the artery lining ( endothelial dysfunction). In one study of 42 women with Syndrome X, those with severe endothelial dysfunction had a 30% increased risk of developing heart disease at 10 years. Syndrome X patients often must undergo repeated hospital visits and tests for chest pain. Many men and women have multiple angiograms to be sure their chest pain isn’t due to blocked arteries. Even after treatment with medications, many Syndrome X patients continue to have chest pain. Several studies have found that most patients still suffer from persistent chest pain even 12 years after their initial diagnosis.



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