Depression, anxiety, and platelet reactivity in patients with coronary heart disease.

There is considerable epidemiological evidence supporting the association between chronic emotional stress and coronary heart disease (CHD). Emotional factors that have been linked to atherosclerosis and adverse cardiac events include primarily negative affective disorders such as depression, anxiety, anger, and hostility. It is now well established that depression is related not only to the incidence of CHD but also to the prognosis of patients with established disease. In a meta-analysis concerned with the role of depression in the development of coronary artery disease, Rugulies found that individuals with clinical depression have .2.5 times the risk of a myocardial infarction or coronary death as the general population. In patients with established coronary disease, not only is major depression a significant predictor of mortality following acute myocardial infarction, but the level of depressive symptoms has a dose–response relationship with cardiac mortality over several years of follow-up. The importance of other affective disorders in the development and progression of CHD is less well established. Large-scale prospective studies have demonstrated a significant link between anxiety and sudden cardiac death, but studies documenting an association between anxiety and the development of coronary artery disease have been inconclusive. In patients with known CHD, Suls and Bunde found a relatively weak association between anxiety and hard cardiac events. More recent studies, however, have demonstrated that anxiety is an independent predictor of major cardiac events in patients with stable coronary disease. Hostility and anger are felt to represent the potentially harmful aspects of Type A behaviour, and their relationships to CHD have therefore received considerable attention. While some studies have reported that hostility is an important risk factor for CHD, numerous studies have found no association between hostility and cardiovascular disease after adjusting for confounding factors. Anger can precipitate acute myocardial infarction, and a dose–response relationship has been found between level of anger and CHD risk. Studies examining the relationship of trait anger and prognosis in patients with established CHD, however, have yielded inconsistent findings. The precise mechanisms by which negative affectivity may influence the development and prognosis of CHD remain unknown. Negative emotions probably adversely affect behavioural factors such as smoking, diet, exercise, and compliance with medical care, thus increasing the risk of cardiovascular morbidity and mortality. Psychological factors also appear to influence directly biological pathways that are important in the development and progression of CHD. Individuals with depression and hostility have evidence of enhanced cortisol secretion, increased sympathetic activation, and elevated plasma catecholamine levels. Depression is also associated with hypertension, endothelial dysfunction, elevated levels of inflammatory cytokines, and increased platelet reactivity. Indeed, the relationship between depression and platelet function has been the focus of considerable attention in recent years. Platelets share many biochemical similarities with central nervous system neuronal monoamine systems, particularly in the uptake, storage, and metabolism of serotonin. There are similarities in the 5-HT2A receptors in platelets and brain serotonergic neurons, and the platelet and brain serotonin transporters (SERTs) are encoded by the same gene. Given the central role that platelets play in both acute and chronic coronary syndromes, it is not surprising that serotonin-mediated platelet activation has been proposed to be a key pathogenic link between depression and CHD. Several studies have demonstrated higher levels of platelet factor 4, b-thrombomodulin, and P-selectin in patients with depression. Depressed patients have also been shown to have increased activation of platelet glycoprotein IIb/IIIa receptors and increased serotonin-mediated platelet reactivity. It is important to understand, however, that studies examining the relationship between depression and platelet reactivity have yielded inconsistent results, with some studies showing no difference in platelet reactivity between depressed and non-depressed patients. These conflicting