Stress Hormones and Variant Angina: From Episodic Vasospasm to Neuroendocrine Vulnerability

Variant angina remains one of the most intriguing forms of ischemic heart disease.Unlike atherosclerotic coronary artery disease, in which fixed luminal obstruction plays a central role, variant angina is characterized by transient and reversible coronary vasospasm.1) To date, endothelial dysfunction, vascular smooth muscle hyperreactivity, autonomic imbalance, inflammation, oxidative stress, and Rho-kinase activation have all been proposed as mechanisms related to coronary spasm, 2)3) but the biological mediators underlying coronary vasospasm remain unclear.Clinicians have long recognized that emotional stress, sleep disturbances, and fluctuations in autonomic tone can cause vasospastic episodes, implying that neuroendocrine mechanisms may potentially contribute to this condition.3) In this issue, Lee et al. 4) report a prospective single-center observational study evaluating the association between serum stress-related hormones and variant angina.The investigators prospectively enrolled 192 patients admitted with ischemic chest pain who underwent coronary angiography.They divided them into four groups: normal coronary arteries, variant angina, stable angina, and acute coronary syndrome.Serum cortisol, adrenocorticotropic hormone, and norepinephrine were repeatedly measured at several time points, including admission and the day after coronary angiography.Patients with variant angina showed higher serum cortisol levels than the normal coronary group at admission and on the day after angiography.Admission cortisol remained independently associated with variant angina in multivariable analysis.In contrast, adrenocorticotropic hormone and norepinephrine levels did not differ significantly between groups.This study is clinically interesting in several respects.First, variant angina has traditionally been viewed as a disorder of the coronary vessel wall, involving endothelial dysfunction, smooth muscle hypercontractility, and spasm provocation.2) Although these mechanisms are important, they do not fully explain recurrent spasms in patients without obstructive coronary artery disease.By examining stress-related hormones, the authors highlight a broader interaction between systemic stress, neuroendocrine regulation, and coronary vasomotor instability.Second, the finding that cortisol levels were elevated without concurrent increases in adrenocorticotropic hormone or norepinephrine suggests that patients with variant angina