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.1
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.1, 7 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.1, 8
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. 9 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.10 However, large trials have found that hormone therapy increases the risk of heart attack and blood clots.11, 12 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.13 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.14 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.15, 16
References
1. Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol. 1995;25:807-814.
2. Reis SE, Holubkov R, Conrad Smith AJ, et al. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001;141:735-741.
3. Buchthal SD, den Hollander JA, Merz CN, et al. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med. 2000;342:829-835.
4. Chauhan A, Mullins PA, Thuraisingham SI, Taylor G, Petch MC, Schofield PM. Abnormal cardiac pain perception in syndrome X. J Am Coll Cardiol. 1994;24:329-335.
5. Cannon RO, 3rd, Quyyumi AA, Schenke WH, et al. Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. J Am Coll Cardiol. 1990;16:1359-1366.
6. Pasceri V, Lanza GA, Buffon A, Montenero AS, Crea F, Maseri A. Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol. 1998;31:62-66.
7. Cannon RO, 3rd, Brush JE, Jr., Schenke WH, Tracy CM, Epstein SE. Beneficial and detrimental effects of lidoflazine in microvascular angina. Am J Cardiol. 1990;66:37-41.
8. Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. J Am Coll Cardiol. 1986;7:479-483.
9. Cox ID, Hann CM, Kaski JC. Low dose imipramine improves chest pain but not quality of life in patients with angina and normal coronary angiograms. Eur Heart J. 1998;19:250-254.
10. Rosano GM, Peters NS, Lefroy D, et al. 17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X. J Am Coll Cardiol. 1996;28:1500-1505.
11. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/ progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49-57.
12. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus Progestin and the Risk of Coronary Heart Disease. N Engl J Med. 2003;349:523-534.
13. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G. Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation. 2004;109:2518-2523.
14. Johnson BD, Shaw LJ, Buchthal SD, et al. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation. 2004;109:2993-2999.
15. Juelsgaard P, Ronnow Sand NP. Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography: a follow-up study. Int J Cardiol. 1993;39:49-57.
16. Lichtlen PR, Bargheer K, Wenzlaff P. Long-term prognosis of patients with anginalike chest pain and normal coronary angiographic findings. J Am Coll Cardiol. 1995;25:1013-1018.
