Coronary artery disease – stress and immunity
In this review Roger Ho and colleagues discuss how stress hormones through affecting different components of the immune/inflammatory reaction may in turn contribute to the development of coronary artery disease (CAD).
Recent evidence indicates that acute and chronic psychological stress, such as intense anger, low socioeconomic status, work stress, social isolation, depression, anxiety and hostility are associated with the development of CAD. For example, high levels of hostility have been found to be associated with increased cortisol responses to anger-inducing interpersonal challenge.
Chronic stress can be an extremely detrimental phenomenon, and it is not surprising to find proinflammatoryphenomena occurring during chronic stress since the system maintains excitability, including that of immune origin.
Recent evidence indicates that acute and chronic psychological stress, such as intense anger, low socioeconomic status, work stress, social isolation, depression, anxiety and hostility are associated with the development of CAD.
Ho et al. outline the following mechanisms that may play a significant role in the pathogenesis of CAD:
- Effect of stress hormones on leukocytes circulation and trafficking, chemotaxis, endothelial dysfunction and expression of cell adhesion molecules
- Effect of stress on the production of proinflammatory cytokines
- The link between depression, infection and coronary artery disease
Stress Leading to Chemotaxis via Changes in Endothelium Function
Thus, for example, under high psychological stress, L-selectin from NK cells do not contribute to mobilisation and CD62+ NK cells will be retained in the vascular marginating pool or in the extravascular tissue. Moreover, there is an increased concentration of adhesion molecules such as ICAM-1 and CD 11a. The increased concentration of adhesion molecules causes the CD62- NK cells to stop rolling and adhere to the site of increased adhesion molecules. Endothelial dysfunction also results in recruitment and adhesiveness of T lymphocytes and platelets.
Further down this road, Activated T cells, in turn, produce proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α), interleukin (IL)-l and IL-6, which stimulate macrophages and vascular endothelial cells and amplify the downstream inflammatory process.
Stress and Coronary Artery Disease – the link to Changes in Monocytes and Cytokines
For example, Douglas L Mann suggested suggested that the short-term expression of stress-activated cytokines within the heart may be an adaptive response to stress, whereas long-term expression of these molecules may be frankly maladaptive by producing cardiac decompensation. Cesari et al. found that proinflammatory cytokines predicted cardiovascular events in older persons. For example, IL-6 is significantly associated with coronary artery disease (CAD), stroke and congestive heart failure (CHF) and is a strong independent predictor for increased mortality in unstable CAD.
The Link between Stress, Coagulation and Atherosclerosis
As per the literature cited in this review, adverse social circumstances and psychosocial factors in childhood increase the concentrations of acute phase proteins such as plasma fibrinogen in adulthood and this increases the subsequent risk of CAD.
Furthermore, lonely individuals also displayed greater fibrinogen response to stress. Chronic psychosocial stressors increase both haemostatic factors (e.g. Factor VII) and acute phase proteins (e.g. fibrinogen). Fibrinogen is thought to promote atherosclerosis by promoting platelet aggregation, enhancing release of endothelial-derived growth factors, stimulating smooth muscle cell proliferation and increasing plasma and whole blood viscosity. Acute and chronic stress may activate the coagulation cascade and lead to thrombus formation and myocardial infarction (MI).
And, in addition, there is robust evidence from epidemiological studies and meta-analyses that higher levels of acute phase proteins such as CRP and fibrinogen predict future cardiovascular death and are associated with low socioeconomic status.
The authors explore some future directions, such as the possibility of modulating immunity through coping with stress and reducing the psychosocial risk for cardiac conditions, or through interventions such as cognitive therapy, relaxation training and behavioral modifications.
This may also include C-reactive protein monitoring that may identify the depressed or anxious patients who would most benefit from a strategy of early prevention of cardiovascular disease, or the need for prospective studies of depressed patients, measuring a wide array of inflammatory markers in order to identify those which are superior to the others in predicting CAD.
SOURCE: Ann Acad Med Singapore 2010, 39(3): 191
