Platelets, coronary heart disease, and stress Lena Brydon , Kesson Magid, Andrew Steptoe The leading cause

of death in the Western world is coronary heart disease. The development coronary heart disease has been correlated with psychosocial factors such as chronic psychological stress. Such stress is seen in individuals that are prone to hostility and depression as well as those who are of low socioeconomic status. These individuals show elevated levels of platelet-leukocyte interactions. These interactions form platelet-leukocyte aggregates, and the interaction of leukocytes with the endothelium of arteries is the cause of the inflammatory process of atherosclerosis. Further support for the involvement of platelets in coronary disease comes from successful usage of anti-platelet drugs, such as Aspirin, in the past and currently. The mechanisms of platelet and leukocyte activity have been assessed by measuring platelet-leukocyte aggregates. Levels of circulating platelet-leukocyte aggregates is increased by acute psychological stress, and in patients with cardiac symptoms, this effect is seen to be prolonged. While most of the evidence is presently cross-sectional and the activation of platelets has not been demonstrated to mediate atherosclerosis or other cardiac symptoms, platelet activation is a highly plausible mechanism which links coronary heart disease with psychological stress. Future studies that investigate the levels of platelet activation in how they correlate with potential coronary heart disease are essential. Chronic Stress Accelerates Atherosclerosis in the Apolipoprotein E Deficient Mouse While conventional factors such as cholesterol and blood pressure are associated with coronary heart disease, these risk factors do not explain and account for the variation seen in heart disease. This suggests that there are additional risk factors to be considered. Past studies have suggested that high levels of psychological stress are correlated with the development of coronary heart disease. The study created a chronic stress protocol and investigated its effects on the development of atherosclerosis in apolipoprotein E knockout mice. Both male and female mice, 2-3 in the same cage, were stressed by alternating immobilizing the mice in a well and exposing them to rat odor. All of the mice were weighed after 24 weeks and cervical dislocation was done by the investigators. Blood was collected for hormone analysis and aortae were prepared for imaging. These aortae were analyzed for the amount of atherosclerosis. It was found that there was a positive linear correlation with the area of atherosclerosis and the duration of stress exposure. Chronically stressed mice also weighed less, which was evidence for the physiological effect of stress. Blood samples also indicated a higher level of corticosterone in the mice expose to longer durations of stress. The findings show that atherosclerosis is increased by chronic psychological stress even if the stress is mild. While additional studies must be undertaken to investigate the mechanism and contributions of these factors, this study contributes experimental support for the notion that cardiovascular disease is affected by psychological stress and that the acceleration of atherosclerosis may be the underlying mechanism.

Salivary cortisol responses to mental stress are associated with coronary artery calcification in healthy men and women It has been suggested from past and recent studies that one of the most prominent risk factors for coronary heart disease is psychological/psychosocial stress. Unfortunately, the mechanisms through which stress contributes to the development of coronary heart disease are poorly understood. Much testing regarding psychophysiological stress has aimed to measure cardiovascular response. However, it has been shown that the hypothalamic pituitary adrenal axis is also involved in the stress response because it is responsible for releasing cortisol into the bloodstream. The study aimed to examine the association between a cortisol response to mental stress and sub-clinical coronary atherosclerosis. 514 healthy men and women were subjected to mental stressors such as a Stroop test and a mirror tracing task. Calcification of the coronary artery was measured by electron beam computed tomography and cortisol levels were measured through saliva. It was found that older patients without a history of coronary heart disease showed greater calcification of the coronary artery due to a heightened cortisol reactivity. This is supportive of the idea that heightened hypothalamic pituitary adrenal activity is a risk factor for coronary heart disease. Blood Pressure Reactivity to Psychological Stress and Coronary Calcification in the Coronary Artery Risk Development in Young Adults Study

It has been long hypothesized that individuals who experience psychological stressors that result in a large increase in blood pressure are at an increased risk for atherosclerosis. There have been only a few studies that have examined this potential correlation in humans. There has been an absence of acceptable methods to measure atherosclerosis in individuals who have not been diagnosed with coronary heart disease. New techniques, however, are noninvasive and allow for a measurement of atherosclerosis in the carotid artery. This study aimed to investigate whether or not changes in blood pressure due to psychological stress predicted coronary calcification in young adults. 2816 black and white women, all aged 20 to 35 years, were evaluated in 1987-1988 for the study. They were subjected to laboratory stressors such as video game and star tracing tasks. Their blood pressures were recorded, and thirteen years later, coronary calcification was measured through computed tomography. It was found that 9.3% of the participants had coronary calcification. A change of 10 mm Hg in systolic blood pressure during the video game testing was found to increase the chances of having coronary calcification by 24%. The star tracing activity was not associated with any coronary calcification. Therefore, it was concluded that the psychological stress associated with the completion of a video game caused a blood pressure change that predicted the occurrence of coronary calcification thirteen years later. At the time, this study was one of the first to measure and correlate stress-induced blood pressure reactivity to the calcification of coronary arteries.

Exaggerated Blood Pressure Responses During Mental Stress Are Prospectively Related to Enhanced Carotid Atherosclerosis in Middle-Aged Finnish Men The magnitude of reactions to and effects from laboratory-induced stress, particularly in regards to cardiovascular and hemodynamic reactions, has been associated with the immediate onset of cardiovascular diseases. It is more unclear, however, whether these reactions relate to the gradual development of coronary heart disease. Previous studies have examined crosssectional relationships between blood pressure and carotid intima-media thickness. Changes in blood pressure were brought about by laboratory challenges and stressors. This study took men from four separate age cohorts and subjected them to a standardized mental stress battery. Their blood pressures and heart rates were recorded and carotid intima-media thickness was assessed. After 7 years, carotid intima-media thickness measures were used as markers of atherosclerosis. 756 men were evaluated for the study. It was found that the level of stress and systolic blood pressure were positively correlated to carotid intima-media thickness. Diastolic blood pressure was less strongly correlated to carotid intima-media thickness. It was concluded that systolic blood pressure reactivity due to psychological stressors and challenges is prospectively related to carotid intima-media thickness. The study was limited by gender and geography. The study was only done on middle-aged Finnish men, which limits the ability to generalize results to more populations. Also, there may have been co-occurring factors with hemodynamic reactivity in individuals could have played a role during the study. 866 665 3578