Synonyms: microvascular angina
Anginal syndrome but with normal coronary arteries. There are two theories which explain cardiac syndrome X:
- The ischaemic theory where there is abnormal coronary microvascular function.
- The non-ischaemic theory where there is altered pain perception and myocardial hypersensitivity.
Kemp introduced the term 'cardiac syndrome X' (CSX) in 1973, to describe patients with exercise-induced angina and normal coronary angiograms. However, it is unsatisfactory. It implies uncertainty around the aetiology and perhaps an apocryphal status as a disease entity. It may also be confused with 'metabolic syndrome', sometimes referred to as 'syndrome X'.
Along with a better name, such as microvascular angina, firmer diagnostic criteria are desirable; first, to facilitate more meaningful research and secondly, to permit evidence-based practice. The classic diagnosis is effort-induced angina-like chest pain, ST-segment depressions on stress testing and normal coronary arteries on angiography.
There is no evidence of coronary spasm. It is thought that the pathology lies in the microvasculature and this is not demonstrated on coronary angiography. There also appears to be endothelial dysfunction.
Since the syndrome was first described in 1967, the incidence has been rising. This may represent a true rise in rate, a rise in the willingness of clinicians to make the diagnosis, or both. The literature comes from all over the world, suggesting that the disease has a universal distribution.
In contrast to coronary artery disease (CAD), it is rather more frequent in women than in men and tends to affect patients between the ages of 40 and 50. Women who present with acute coronary syndromes are more likely to have non-obstructive disease with prevalence rates of approximately 20%. Black and Hispanic women are more frequently affected.
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These are in common with CAD:
- Insulin resistance or overt diabetes - usually type 2.
- Patients tend to be more unfit and out of condition than others of similar age and sex.
- Low-grade chronic inflammation.
Hypertension and diabetes used to be regarded as criteria that exclude permission to diagnose cardiac syndrome X (CSX), as they are known to be associated with endothelial dysfunction; however, as this would seem to be an underlying pathology, such a provision is illogical. Chronic inflammation is also associated with microvascular dysfunction in the absence of coronary atherosclerosis. The association between diabetes and coronary heart disease (CHD) is very well known but what is less well appreciated is the similar association with rheumatoid arthritis.
- Chest pain occurs on exertion but it may not be typical of CAD in its site and provoking factors.
- Symptoms are often severe and disabling.
As mentioned above, the history of angina should be typical and precipitated largely or wholly by exercise.
There are no characteristic clinical signs but the patient is more likely to be:
- In poor physical condition
The whole spectrum of causes of chest pain must be considered; however, for special consideration are:
- Prinzmetal's angina
Investigations should be as for CHD:
- FBC (to exclude anaemia or polycythaemia).
- U&E (if starting an angiotensin-converting enzyme (ACE) inhibitor).
- LFTs (before starting a statin).
- Fasting lipids (with a view to adjustment by diet or drugs).
- Fasting blood glucose (may show impaired glucose tolerance or overt diabetes).
Cardiac syndrome X (CSX) is usually a diagnosis of exclusion. Non-cardiac aetiologies of chest pain, including musculoskeletal, psychiatric, gastrointestinal, and pulmonary disorders, must be excluded. Those with angina-like chest pain, and even some with atypical features, including more frequent or persistent pain and inconsistent response to sublingual nitrates, should undergo stress testing.
Coronary artery spasm should be excluded by appropriate provocation tests. Endothelial dysfunction can be shown by epicardial coronary artery diameter response to acetylcholine.
Down-sloping ST-segment depression remains a diagnostic criterion.
Other tests are used but many of these are still largely research procedures.
The goals of treatment are to improve symptoms. This may be by using anti-anginal therapies, but also through pain modulation. The response to treatment is somewhat variable.
- Exercise regimes have a beneficial effect.
- Weight loss reduces insulin resistance.
- Stop smoking if applicable.
- In patients refractory to other forms of treatment, transcutaneous electrical nerve stimulation (TENS) or spinal cord stimulation (SCS) may be of value.
- Beta-blockers are regarded as first-line. There may be a variable response in improving chest pain. They work by lowering adrenergic tone and reducing myocardial oxygen demand, as well as enhancing endothelium-dependent vasodilation.
- The efficacy of calcium-channel blockers hasn't been proven yet, but they could be used in combination with beta-blockers.
- Sublingual nitrates may benefit symptomatic episodes, but long-acting nitrates have proven disappointing.
- Xanthine derivatives such as aminophylline, have been shown to improve the time to exercise-induced angina, time to ST depression, and the magnitude of ST depression in patients with cardiac syndrome X (CSX). They could be used where chronic airways disease and CSX co-exist.
- ACE inhibitors are beneficial for endothelial dysfunction, as demonstrated by their effect on microalbuminuria. However, there is a lack of consistent well-constructed evidence to support their use.
- Statins are used where cholesterol is elevated but they also stabilise the endothelial membrane.
- Imipramine may be beneficial in pain modulation.
- Even in women without diabetes, metformin may improve vascular function and decrease myocardial ischaemia. Larger trials are required.
The pathology is in very small arteries that are too small for reconstruction.
- The quality of life is generally poorer than life expectancy. Symptoms will improve in about a third, but 10-20% become worse. With such a low mortality but high morbidity, questions are invariably raised about the psychological component to this disease.
- Prognosis may be adversely affected by concomitant coronary microvascular dysfunction. Cardiac syndrome X (CSX) patients with this accompanying condition are more likely to develop atherosclerotic CAD in the future and have higher cardiovascular event rates. Patients who have myocardial ischaemia on magnetic resonance spectroscopy have significantly greater frequency of adverse cardiovascular events.
The aim of management is to improve the quality of life.
The BMA recommends that, for the purpose of the Quality and Outcomes Framework, CSX should not be included in the CHD register.
Presumably, avoiding obesity and keeping physically active would protect against the condition.
Further reading & references
- Seiden SW; Evaluating patients with persistent chest pain and no obstructive coronary artery disease. JAMA. 2009 Aug 12;302(6):622; author reply 623-4.
- Banks K, Lo M, Khera A; Angina in Women without Obstructive Coronary Artery Disease. Curr Cardiol Rev. 2010 Feb;6(1):71-81.
- Vermeltfoort IA, Raijmakers PG, Riphagen II, et al; Definitions and incidence of cardiac syndrome X: review and analysis of clinical Clin Res Cardiol. 2010 Aug;99(8):475-81. Epub 2010 Apr 21.
- Management of Stable Angina Pectoris, European Society of Cardiology (2006)
- Lanza GA; Cardiac syndrome X: a critical overview and future perspectives. Heart. 2007 Feb;93(2):159-66. Epub 2006 Jan 6.
- Cannon RO 3rd; Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol. 2009 Sep 1;54(10):877-85.
- Shaw LJ, Shaw RE, Merz CN, et al; Impact of ethnicity and gender differences on angiographic coronary artery Circulation. 2008 Apr 8;117(14):1787-801. Epub 2008 Mar 31.
- Solomon DH, Goodson NJ, Katz JN, et al; Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006 Dec;65(12):1608-12. Epub 2006 Jun 22.
- de Vries J, Dejongste MJ, Durenkamp A, et al; The sustained benefits of long-term neurostimulation in patients with refractory chest pain and normal coronary arteries. Eur J Pain. 2007 Apr;11(3):360-5. Epub 2006 Jun 9.
- Jadhav S, Ferrell W, Greer IA, et al; Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2006 Sep 5;48(5):956-63. Epub 2006 Aug 17.
|Original Author: Dr Hayley Willacy||Current Version: Dr Hayley Willacy||Peer Reviewer: Prof Cathy Jackson|
|Last Checked: 20/02/2012||Document ID: 1909 Version: 23||© EMIS|
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