Trait Anger, Hostility, Serum Homocysteine, and Recurrent Cardiac Events After Percutaneous Coronary Interventions

The mortality rate of patients with coronary artery disease (CAD) has steadily decreased, thanks to advances in percutaneous coronary interventions (PCIs).1 However, in South Korea, cardiovascular disease, including myocardial infarction, remains a major cause of death.2 Restenosis rates after PCIs vary widely from less than 10% to 60%.1, 3, 4 In addition, the rate of recurrence of cardiac events (eg, emergency department visits and rehospitalization due to restenosis) within 6 months after PCIs is almost 15%,5–7 and recurrence of cardiac events confers a higher risk of fatal myocardial infarction. Therefore, secondary prevention of recurrent cardiac events remains important, and research to identify factors that may contribute to recurrent cardiac events among patients with CAD after PCI is essential. Previous investigators have identified characteristics of patients, including sex, age, hypertension, smoking, serum level of cholesterol, obesity, diabetes, and lack of physical activity, as predictors of development and progression of CAD.7–9 Recently, serum level of homocysteine has also been identified as a risk factor for development and progression of CAD10, 11 and restenosis in patients undergoing PCIs.12, 13 Homocysteine is an intermediate metabolite of methionine. 14 High concentrations of homocysteine markedly increase the risk for development and progression of CAD by damaging vascular endothelial cells and stimulating prothrombin responses and proliferation of smooth muscle cells.15–17 Behavioral pathways that may link high serum levels of homocysteine to CAD (eg, lack of physical activity and smoking) have been suggested.18, 19 However, these behavioral mechanisms do not explain fully the association between serum level of homocysteine and recurrent cardiac events. As a result, interest in the relationship among psychosocial factors, biological factors, and development of CAD is growing.20 Hostility has a positive correlation with serum levels of homocysteine.21, 22 High levels of hostility are predictive of CAD23 and restenosis in patients who undergo PCI.24 People with a higher level of hostility tend to experience more intense and frequent feelings of anger than do people with a lower level of hostility.21, 25 Anger is predictive of the occurrence of CAD9 and recurrent cardiac events after successful PCIs.26 The potential link among trait anger, hostility, and serum level of homocysteine in patients with CAD after PCIs as a tentative mechanism leading to recurrent cardiac events has not been fully explored. The purpose of this study was to examine the relationship among trait anger, hostility, serum level of homocysteine, and recurrent cardiac events in patients undergoing PCIs. The following 5 hypotheses were proposed. Hypothesis 1: The risk of recurrent cardiac events will be higher in patients with higher trait anger once age, sex, body mass index, regular exercise, smoking behavior, and serum levels of total cholesterol, triglycerides, and high- and low-density lipoprotein cholesterol are controlled for. Hypothesis 2: The risk of recurrent cardiac events will be higher in patients with higher levels of hostility once traditional risk factors are controlled for. Hypothesis 3: The risk of recurrent cardiac events will be associated with higher serum levels of homocysteine once traditional risk factors are controlled for. Hypothesis 4: Patients with high trait anger and high homocysteine level will have the shortest time to recurrent cardiac events after traditional risk factors are controlled for. Hypothesis 5: Patients with high hostility and high homocysteine level will have the shortest time to recurrent cardiac events once traditional risk factors are controlled for.