Insights into the Pathogenetic Mechanisms of Unstable Angina
Authors: Cohen Marc , Fuster Valentin 
Published: April 2009

Patients with unstable angina and/or non-Q-wave infarction constitute a group that is at high risk for progression to acute myocardial infarction or sudden death. Furthermore, in spite of maximal medical therapy, a large fraction of these patients experience recurrent episodes of myocardial ischemia prompting surgical revascularization or coronary angioplasty. In prior studies of patients with unstable angina, the incidence of myocardial infarction within 1 month of hospitalization was 8–13%, and the incidence of death was about 4%. Between 3 months and 1 year after presentation, the cumulative rate of infarction or death increased to 10–14 and 8–10%, respectively. That is, most recurrent ischemic events occur within the first 3 months after the onset of symptoms. In the subset of patients with pain at rest or with electrocardiographic changes at the time of admission, the prognosis is even worse. The rate of myocardial infarction or death in such patients ranged between 14 and 21 % during the first 3–4 months after onset of symptoms. Crossover to surgical therapy because of recurrent ischemic pain was also common, occurring in 30–50% of the patients at 3 months. Recent advances in understanding the pathophysiology of these two syndromes suggest that an aggressive antithrombotic regimen could be of great benefit in preventing progression to acute coronary occlusion and death. Pathologic investigations strongly suggested that plaque fissuring and subsequent overlying thrombosis were the major components in the process of unstable angina progressing to myocardial infarction and/or sudden death. This hypothesis has been substantiated by recent pathologic studies of patients who died shortly after the onset of unstable angina. Examination of the coronary arteries revealed not only plaque fissuring with superimposed layers of thrombus in the majority of the cases, but also evidence of distal thromboembolism from these foci. In vivo coronary arteriography in patients with unstable angina highlighted the progression of prior coronary stenoses, even to total occlusion, and the eccentric and irregular angiographic morphology of the ischemia- producing lesions. Furthermore, intracoronary thrombus is often seen at these sites, especially when arteriography is carried out soon after rest pain. These observations also suggested that plaque rupture may have occurred. Intraoperative angioscopy has revealed ruptured plaques in patients with progressive unstable angina, while those with rest pain had complicating thrombi. Patients with unstable angina also have biochemical evidence of activation of both the coagulation systems and platelets. Lastly, the beneficial response to antithrombotic therapy with aspirin, heparin, or both is a strong indicator that a thrombotic process is active at least at some stage in the evolution of unstable angina. Vasoconstriction may also play a role in the pathophysiology of unstable angina. Studies using calcium channel blockers indicate that the frequency of recurrent pain is diminished with these agents; however, none of these studies observed a difference in the rate of fatal myocardial infarction or significantly reduced the 3- to 6-month crossover to revascularization. However, only antithrombotic regimens have been shown to reduce the rate of myocardial infarction and/or death in patients with unstable angina.