Coronary artery spasm: mechanisms, risk factors, and translational strategies for precision management

Coronary artery spasm (CAS) is a major form of coronary vasomotor dysfunction within ischemia with non-obstructive coronary arteries (INOCA). Despite ethnic and geographic variation in prevalence, CAS is underrecognized because confirmation often requires pharmacological provocation testing that is unavailable in many centers. Clinically, CAS ranges from silent ischemia and angina to acute myocardial infarction, malignant arrhythmias, heart failure, and sudden cardiac death. Evidence suggests that spasm often occurs at sites with mild atherosclerosis and that its risk profile differs from atherosclerotic cardiovascular disease, with more consistent links to smoking, inflammatory burden, and genetic susceptibility, while associations with hypertension and diabetes remain inconsistent. Advances in invasive coronary function testing and recognition of microvascular spasm support an integrated framework involving endothelial dysfunction, vascular smooth muscle hyperreactivity, inflammation-oxidative stress, and autonomic dysregulation. This review synthesizes mechanistic and clinical evidence across these domains, highlights translational opportunities for phenotype-informed risk stratification and precision management, and outlines key research priorities to improve CAS care.