Syndrome X

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The terms Syndrome X or Metabolic syndrome X may also be referring to metabolic syndrome.

Synonyms and key words: Microvascular angina

Overview

(Cardiac) syndrome X is angina (chest pain) associated with objective evidence of myocardial ischemia in the absence of epicardial coronary artery disease. The disorder has been hypothesized to be a disorder of the coronary microvasculature rather than the large caliber epicardial coronary arteries.

Pathophysiology

In a large percentage of patients, there is microvascular dysfunction. Specifically, the microvasculature cannot dilate to accomadate increased blood flow during exertion to meet the needs of myocardial metabolism.

Several other pathophysiologic mechanisms have been proposed with variable data to support them:

Adenosine as a Cause of Chest Pain

Both endogenous and exogenous adenosine can cause chest discomfort through stimulation of sensory nerves in the heart [1][2]. Huang et al have demonstrated that both A1- and A2-adenosine receptors are present on the cardiac sensory nerve endings of dorsal root ganglion neurons. These sensory neurons are active in the absence of ischemia, but become further activated during myocardial ischemia[2].

An Extension of Dysautonomias

Syndrome X has been associated with dysautonomias and with a greater frequency of autonomic symptoms such as tachycardia, dyspnea, dizziness, and paresthesias [3]. It has therefore been hypothesized that Syndrome X may be an extension of abnormalities of the autonomic nervous system.

"Female Pattern" of Atherosclerosis

It has also been speculated that although the coronary arteriogram may appear normal, there may in fact be diffuse atherosclerosis present in what has been termed "a female pattern" of disease.

Enhanced Pain Sensitivity

Patients with normal coronary arteries and myocardial ischemia have a lower pain threshold and a lower tolerance to pain induced by adenosine [4].

Panic Disorder

Approximately one third of patients with angina pectoris and normal coronary arteries are diagnosed with panic disorder [5].

Epidemiology and Demographics

Syndrome X occurs more often in young women. Some studies have found an increased risk of other vasospastic disorders in syndrome X patients, such as migraine and Raynaud's phenomenon.

Natural history, complications, and prognosis

Syndrome X does not appear to be associated with an excess of major coronary events.

The absence of significant coronary artery disease on coronary angiography is associated with a good prognosis. Among 3,136 patients with normal angiograms, the 7 year survival rate was 96%[6].

Risk Factors

Female gender and left ventricular hypertrophy are associated with an excess risk of Syndrome X. The onset in women often occurs after menopause.

Other Conditions to Distinguish Syndrome X From

Syndrome X should be distinguished from Prinzmetal's angina, a disorder which involves spasm of the main epicardial coronary arteries. Syndrome X involves dysfunction of the downstream microvasculature. Syndrome X must also be distinguished from esophageal spasm.

Diagnosis

Syndrome X is a diagnosis of exclusion. The diagnostic criteria are as follows:

ESC Guidelines for investigation in patients with Syndrome X (DO NOT EDIT)[7]

Class I

1. Resting echocardiogram in patients with angina and normal or non-obstructed coronary arteries to assess for presence of ventricular hypertrophy and/or diastolic dysfunction. (Level of Evidence: C)

Class IIb

1. Intracoronary acetylcholine during coronary arteriography, if the arteriogram is visually normal, to assess endothelium-dependent coronary flow reserve, and exclude vasospasm. (Level of Evidence: C)

2. Intracoronary ultrasound, coronary flow reserve, or FFR measurement to exclude missed obstructive lesions, if angiographic appearances are suggestive of a nonobstructive lesion rather than completely normal, and stress imaging techniques identify an extensive area of ischaemia. (Level of Evidence: C)

Treatment

The mainstay of treatment in patients with Syndrome X are calcium channel blockers, such as nifedipine and diltiazem. Other therapies include:

ESC Guidelines for pharmacological therapy to improve symptoms in patients with Syndrome X (DO NOT EDIT)[7]

Class I

1. Therapy with nitrates, beta blockers, and calcium channel blockers alone or in combination. (Level of Evidence: B)

2. Statin therapy in patients with hyperlipidaemia. (Level of Evidence: B)

3. ACE inhibitors in patients with hypertension. (Level of Evidence: C)

Class IIa

1. Trial of therapy with other anti-anginals including nicorandil and metabolic agents. (Level of Evidence: C)

Class IIb

1. Aminophylline for continued pain, despite Class I measures. (Level of Evidence: C)

2. Imipramine for continued pain, despite Class I measures. (Level of Evidence: C)

References

  1. http://www.nejm.org/doi/full/10.1056/NEJM200210243471717
  2. 2.0 2.1 Huang MH, Sylvén C, Horackova M, Armour JA (1995). "Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P.". Am J Physiol. 269 (2 Pt 2): R318–24. PMID 7544544.
  3. Katon W, Hall ML, Russo J, Cormier L, Hollifield M, Vitaliano PP; et al. (1988). "Chest pain: relationship of psychiatric illness to coronary arteriographic results". Am J Med. 84 (1): 1–9. PMID 3337115.
  4. Lagerqvist B, Sylvén C, Waldenström A (1992). "Lower threshold for adenosine-induced chest pain in patients with angina and normal coronary angiograms". Br Heart J. 68 (3): 282–5. PMC 1025071. PMID 1389759.
  5. Mukerji V, Beitman BD, Alpert MA, Lamberti JW, DeRosear L, Basha IM (1987). "Panic disorder: a frequent occurrence in patients with chest pain and normal coronary arteries". Angiology. 38 (3): 236–40. PMID 3565851.
  6. Kemp HG, Kronmal RA, Vlietstra RE, Frye RL (1986). "Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study". J Am Coll Cardiol. 7 (3): 479–83. PMID 3512658.
  7. 7.0 7.1 Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). "Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology". Eur Heart J. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367.

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