The Clinical Characteristics Of Patients With Variant Angina And Inflammation-associated Molecular Mechanisms

Objective and Backgroud:Variant angina (VA) is a unique entity of coronary artery disease (CAD), it is caused by occlusive epicardial coronary spasm resulting in transmural myocardial ischemia and severe cardiac events. Previous studies suggest that both calcium antagonists (CCB) and isosorbide dinitrates are effective for suppressing chest pain attacks in patients with VA. However, less data is available regarding sex differences in patients with VA and Chinese population. The present study, accordingly, was to evaluate the clinical characteristics of Chinese patients with VA and their gender differences retrospectively.Methods:From January 2003 to December 2009, a total of 312 patients were diagnosed to have a spontaneous attack of VA at our hospital. Their clinical findings were collected and the differences were compared in the aspects of risk factors, clinical features, angiographical findings between female patients and male patients.Results:VA affected men(87.8%) more frequently than women, the common risk factors included smoking, hypertension and hyperlipedia,17.6% of patient had allergy history.18.9% of patients suffered from various arrhythmias including ventricular tachycardia,ventricular fibrillation, sinus bradycardia and AV block during chest pain. Significant fixed coronary obstruction occurred in 54.8% of patients, and 7.1% of patients accompanied with coronary myocardial bridge. Nitrates, CCB and placement of stents were extremely effective in preventing VA. The female patients had less history of smoking (10.5%vs 78.8%,p<0.01), more family history of coronary artery disease (31.6% vs 11.3%, p<0.01), more incidence of ventricular tachycardia (13.2% vs 3.6%,p<0.05) and ventricular fibrillation (7.9% vs 1.8%, p<0.05) during angina attacks.Conclusion:VA is caused by coronary artery spasm and usually accompanied with arrhythmias. It can cause myocardial infarction and sudden cardiac death without treatment promptly. CCB should be used in preventing VA except traditional treatment. Placement of stents in the coronary arteries with severe fixed obstruction is helpful. Female patients with VA had the characteristics of less history of smoking, more family history of CAD, more occurrence of ventricular tachycardia and ventricular fibrillation. Objective and Backgroud:Variant angina (VA) is characterized by attacks occurring at rest and associated with transient ST segment elevation, it is caused by occlusive epicardial coronary artery spasm (CAS) resulting in transmural myocardial ischemia. Previous studies showed that multiple factors, such as endothelial dysfunction, hypercontractility of vascular smooth muscle, oxidative stress and genetic risk factors were involved in the occurrence of CAS. However, despite the extensive studies, the precise machanisms in VA remain unclear. Previous studies suggest that inflammation may play an important role in the pathogenesis of CAS. The present study was, therefore, to investigate whether inflammatory molecules such as nuclear factor-κB (NF-κB), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) might be involved in the pathogenesis of VA and the effect of simvastatin on C-reactive protein (CRP)-dependent inflammatory activation in monocytes of patients with VA.Methods:Monocytes of patients with variant angina (VA, n=6) and normal controls (controls, n=6) were cultured and stimulated with 20mg/L of CRP for 24 hours. Also 10umol/L of simvastatin was pre-incubated for 2 hours with monocytes in the presence of CRP. The levels of NF-κB, TNF-αand IL-6 were evaluated by enzyme-linked immunosorbent assay (ELISA).Results:The data showed that the levels of NF-κB, TNF-αand IL-6 in baseline status were similar in patients with VA and normal controls. The levels of NF-κB, TNF-αand IL-6 induced by CRP were significantly elevated both in VA and normal controls compared with their baseline status (p<0.01). Patients with VA were detected to have significantly higher NF-κB, TNF-αand IL-6 levels induced by CRP in comparison with normal controls (p<0.01). Simvastatin significantly inhibited the production of NF-κB, TNF-αand IL-6 in monocytes stimulated by CRP both in VA and in normal controls (p<0.01).Conclusion:CRP could induce more NF-κB, TNF-αand IL-6 release in human monocyes of patients with VA than normal controls, suggesting that an enhanced inflammatory response to CRP may be involved in the pathogenesis of VA. Simvastatin could inhibit this response which could provide an insight into the mechanism of anti-inflammation in statins.