What Causes Coronary Artery Spasms
Coronary artery spasms result from dysfunctional endothelium that exposes vascular smooth muscle to vasoconstrictors, combined with an imbalance favoring vasoconstrictor factors over vasodilator factors, leading to hypercontraction of coronary smooth muscle. 1
Primary Pathophysiologic Mechanisms
Endothelial Dysfunction
The fundamental defect in coronary spasm is dysfunctional endothelium that exposes medial smooth muscle to vasoconstrictors including catecholamines, thromboxane A2, serotonin, histamine, and endothelin. 1 This endothelial dysfunction impairs coronary flow-dependent vasodilation due to decreased production and release of nitric oxide. 1 Reduced endothelial nitric oxide activity results in increased calcium sensitivity through enhanced RhoA/ROCK pathway, which is directly involved in the hypercontraction mechanism. 2
Imbalance of Vasoactive Factors
There is a critical imbalance between endothelium-produced vasodilator factors (prostacyclin, nitric oxide) and vasoconstrictor factors (endothelin, angiotensin II) that favors vasoconstriction. 1 This imbalance, combined with enhanced phosphorylation of myosin light chains—an important step in smooth muscle contraction—creates the substrate for spasm. 1
Smooth Muscle Hypercontractility
Coronary spasm represents a hypercontraction of coronary smooth muscle triggered by increased intracellular calcium in the presence of increased calcium sensitivity. 2 The spastic artery is hyperresponsive to nitroglycerin (a nitric oxide donor) and deficient in nitric oxide activity, confirming the role of impaired endothelial function. 3
Contributing Factors and Risk Modifiers
Autonomic Nervous System Involvement
Evidence demonstrates involvement of the autonomic nervous system, with reduced parasympathetic tone and enhanced reactivity of alpha-adrenergic vascular receptors contributing to spasm susceptibility. 1
Inflammatory State
Patients with coronary spasm have endothelial dysfunction combined with low-grade chronic inflammation, evidenced by elevated markers of oxidative stress, enhanced thrombogenesis, and elevated plasma levels of hsCRP and P-selectin. 2
Major Risk Factors
Cigarette smoking is the most important modifiable risk factor for coronary spasm, along with polymorphisms of endothelial nitric oxide synthase and low-grade inflammation. 2, 3 The prevalence is notably higher in Japanese and Korean populations compared to Western populations, likely due to both genetic and environmental factors. 2, 3
Clinical Context and Triggers
Temporal Pattern
Coronary spasm occurs most often from midnight to early morning when patients are at rest and is usually not induced by exercise in the daytime. 2, 3 This circadian variation with early morning predominance indicates higher risk for myocardial infarction. 4
Relationship to Atherosclerosis
Spasm can be superimposed on severe or nonsevere coronary stenosis or occur in angiographically normal coronary artery segments. 1 Even angiographically normal segments often harbor mural atherosclerosis on intravascular ultrasound, predisposing to localized endothelial dysfunction. 4
Transient but Recurrent Nature
The risk for focal spasm is transient but recurrent, and susceptibility to spasm is not constant over time, being dependent on the state of the endothelium. 1
Important Clinical Pitfalls
Do not assume spasm only occurs with obstructive disease: Dynamic obstruction can occur through diffuse microvascular dysfunction due to endothelial dysfunction or abnormal constriction of small intramural resistance vessels, even without epicardial disease. 1
Recognize cocaine as a specific trigger: Coronary spasm is the presumed mechanism underlying cocaine-induced unstable angina and myocardial infarction. 1
Avoid beta-blockers: Beta-blockers have theoretical adverse potential in coronary spasm, and non-selective beta-blockers can promote attacks or prolong the vasospastic state. 1, 5
Understand multivessel involvement increases risk: Multivessel disease is present in 19% of vasospastic angina patients and significantly increases risk of myocardial infarction and death. 4 Patients with multivessel coronary spasm may suffer lethal arrhythmias including advanced AV block, ventricular tachycardia, or ventricular fibrillation. 2