Coronary Artery Vasospasm 

  • Author: Stanley S Wang, MD, JD, MPH; Chief Editor: Eric H Yang, MD   more...
 
Updated: Jan 24, 2011
 

Background

Coronary artery vasospasm, or smooth muscle constriction of the coronary artery, is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. It also plays a key role in the development of atherosclerotic lesions.

In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation.[1] Unlike patients with typical angina, exercise tolerance in these patients was characteristically normal and pain patterns tended to be cyclical with most episodes occurring in the early morning hours without regard to cardiac workload. This syndrome became known as Prinzmetal or variant angina, and was believed to be due to vasospasm in coronary arteries without obstructive lesions. Subsequently, Maseri et al described the clinical, electrocardiographic, and angiographic features of 138 patients with variant angina and concluded that the syndrome is considerably more polymorphic than initially inferred by Prinzmetal.[2]

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Pathophysiology

The pathophysiological mechanisms leading to coronary artery vasospasm are incompletely understood at this time. Coronary arterial tone varies normally through physiological mechanisms, but the degree of vasoconstriction can range along a spectrum from undetectable constriction to complete arterial occlusion. In some patients with partial vasoconstriction, symptoms can arise with activities that exceed a threshold of myocardial demand.[3] In other patients, constriction may be so severe that myocardial ischemia develops at rest. Many observers use the presence of constriction-induced ischemia as the threshold for defining clinical coronary artery vasospasm[4] , which has also been called vasospastic angina or variant angina.

Coronary artery vasospasm can be induced through stimulation of alpha receptors[5] or intracoronary injection of the parasympathetic neurotransmitter acetylcholine[6] , implicating different mechanisms of action.

Acetylcholine causes coronary vasodilation in healthy coronary arteries through the release of endothelial nitric oxide; however, in atherosclerotic arteries, vasoconstriction ensues instead. Patients with coronary artery vasospasm appear to have a heightened vasoconstrictor response to acetylcholine as well as an enhanced response to the vasodilator effects of nitrates, an observation that is consistent with a deficiency of endogenous nitric oxide activity.[4] Thus, nitric oxide deficiency is believed to play an important role in the development of coronary artery vasospasm. This may also explain the correlation between coronary artery vasospasm and increased intimal thickening, as nitric oxide deficiency results in enhanced activity of potent vasoconstrictors and stimulators of vascular smooth muscle proliferation, such as angiotensin II and endothelin 1.[4]

Several genetic polymorphisms that compromise endothelial nitric oxide production have been found to be significantly associated with coronary artery vasospasm.[7] Some have even been found to have prognostic value, including the -786T/C polymorphism.[8]

However, additional studies showing that nitric oxide levels are not decreased at the sites of coronary artery vasospasm dispute the primacy of the role of nitric oxide.[9] Alternative (or coexisting) mechanisms of coronary artery vasospasm include enhanced phospholipase C activity.[10] In addition, coronary artery vasospasm is associated with increased markers of oxidative stress and inflammation, including thioredoxin, C-reactive protein, and monocyte levels.[4] Interestingly, certain behavioral traits (such as type A personality, panic disorder, and severe anxiety) have also been described in association with coronary artery vasospasm.[11]

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Epidemiology

Frequency

United States

The reported prevalence of vasospastic angina varies considerably between clinical studies depending in large part on the geographic location of the population studied as well as the criteria used to test and define the condition.[12] In the United States, the frequency is among the lowest in the world with about 4% of patients undergoing coronary angiography having evidence of focal spasm, when defined as a 75% reduction in artery diameter upon the administration of ergonovine.[13]

International

In France, around 12% of patients had positive ergonovine-based studies[14] , whereas the Japanese literature, from which a preponderance of publications on coronary artery vasospasm originates, reports positive study rates of around 30%.[15] Interestingly, the incidence of coronary artery vasospasm may be increasing in Japan, at least on the basis of provocation of spasm by the administration of acetylcholine.[16]

Mortality/Morbidity

The prognosis of patients with vasospastic angina appears to be dependent upon the degree of coexisting atherosclerotic coronary disease.[17] In patients with no or even single-vessel atherosclerosis, the prognosis is benign with survival rates of up to 99% at 1 year and 94% at 5 years. On the other hand, survival in patients with multivessel atherosclerotic disease fell to 87% at 1 year and 77% at 5 years. Survival rates were also lower in patients with multivessel spasm.[18]

Race

Japanese patients are much more likely to develop coronary artery vasospasm than Caucasian patients. When evaluated by the same team, Japanese patients had a three-fold greater incidence of spasm compared to their Caucasian counterparts even though the two groups of patients had similar average basal coronary tone[19] .

Sex

Variant angina is believed to be more common in female patients[20, 21] , although some prognostic studies of patients with variant angina suggest a male preponderance. Among women, variant angina may be relatively more common in Caucasian patients (22%) than in Japanese patients (11%).

Age

The onset of symptoms occurs at a highly variable age, but, on average, patients are in their 50s when symptoms begin.[22]

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Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Stanley S Wang, MD, JD, MPH  Clinical Cardiologist, Austin Heart South; Assistant Professor of Medicine (Adjunct), University of North Carolina School of Medicine

Stanley S Wang, MD, JD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, American Stroke Association, and Texas Medical Association

Disclosure: Abbott Labs Honoraria Speaking and teaching

Specialty Editor Board

Gregory J Dehmer, MD  Director, Division of Cardiology, Scott & White Healthcare; Professor of Medicine, Texas A&M Health Science Center College of Medicine

Gregory J Dehmer, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, Society for Cardiac Angiography and Interventions, and Society of Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Steven J Compton, MD, FACC, FACP  Director of Cardiac Electrophysiology, Alaska Heart Institute, Providence and Alaska Regional Hospitals

Steven J Compton, MD, FACC, FACP is a member of the following medical societies: Alaska State Medical Association, American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, and Heart Rhythm Society

Disclosure: Nothing to disclose.

Amer Suleman, MD  Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital

Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD  Assistant Professor of Medicine, Director of Coronary Care Unit, University of North Carolina at Chapel Hill School of Medicine

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

References

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