Statins in Variant Angina

Variant angina pectoris (VAP) is a form of angina pectoris that shows transient ST-segment elevation on electrocardio-gram during an attack of chest pain and is caused by coronary artery spasm. Although the pathogenesis of coronary artery spasm has not been fully elucidated, endothelial dysfunction and enhanced vascular smooth muscle contractility play major roles in the pathogenesis of coronary artery spasm. Other contributing factors of coronary artery spasm include increased oxidative stress, inflammation, magnesium deficiency, genetic susceptibility, and imbalance in autonomic nervous activity. Statins have been demonstrated to significantly improve the prognosis and outcome of patients with atherosclerosis mainly because statins can lower low density lipoprotein (LDL)-cholesterol concentration. 4)5) However, recent studies suggested that statins may affect the cardiovascular system beyond their effect on the lipid profile (called pleiotropic effects). 6) Pleiotro-pic effects of statins include improvement of endothelial dys-function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory responses, and stabilization of atherosclerotic plaques, which may provide a cardiovas-cular benefit beyond that expected from LDL-cholesterol lowering alone. 7)8) These effects of modulated endothelial function and reduced inflammatory processes have been pointed out as one of the possible mechanisms of reducing coronary artery va-sospasm in VAP. 8) Recent clinical evidences also showed that combined therapy with a statin and a calcium channel blocker may attenuate coronary vasoconstriction as well as systemic en-dothelial dysfunction in patients with VAP. also support the evidence that the use of atorvastatin, regardless of dosage, could improve systemic endothelial function as measured by flow mediated dilation of the brachial artery in patients with VAP. Collectively, statin might modify the underlying patho-genesis of coronary artery spasm and be a novel therapeutic drug for coronary artery spasm in patients with VAP. Kim et al. 11) also hypothesized that atorvastatin 40 mg could improve more endothelial function and carotid intima media thickness than those of atorvastatin 10 mg. It has not been demonstrated the dose-dependent effects of statin therapy on vascular function in patients with VAP. Experimental studies support this hypothesis that statins can dose-dependently increase the production of nitric oxide by activation of endothelial nitric oxide synthase and increasing its mRNA half-life, independent of cholesterol levels. 12)13) Clinical evidence also suggested that intensive lipid-lowering therapy with statin provides significant clinical benefit beyond lipid-lowering therapy in patients with atherosclerosis, which is suggestive of dose-dependent pleiotropic effects of statin. in this issue of J Cardiovasc Ultrasound concluded that the use of …