Effects of negative affect, caregiving stress, and cardiovascular risk factors on coagulation responses to acute psychological stress

Research suggests that depression is associated with heightened risk of cardiovascular morbidity and mortality, independent of sociodemographic, behavioral and medical factors. Chronic stressors, such as caring for a spouse with Alzheimer's disease may contribute to CVD risk, partly through increased symptoms of negative affect and heightened platelet activation.;Objectives: (1) To investigate cross-sectional and longitudinal associations between negative affect and platelet activation. (2) To investigate whether the magnitude of these associations is greater among dementia caregivers compared to non-caregivers. (3) To explore the impact of age, gender, preexisting cardiovascular disease, and medication usage (particularly Hormone Replacement Therapy) on platelet activation among caregivers.;This study utilized a pre-existing data set consisting of 99 caregivers and 50 non-caregivers (average age 71 years), who were assessed over a 3-year period. Caregiver burden and negative affect were assessed using the Role Overload Instrument and the depressive and anxious symptom subscales of the Brief Symptom Inventory. Plasma norepinephrine levels were assayed using enzyme linked immunoabsorbent assay (ELISA). Three measures of platelet activation were obtained through flow cytometric analyses: (1) Glycoprotein IIb/IIIa expression, (2) P-selectin expression, and (3) % platelet aggregates. In order to elicit platelet and norepinephrine reactivity, participants completed an acute stress test, and blood was drawn at three time-points (baseline, post-speech, and after 14 minutes of recovery).;Four separate studies are presented as separate manuscripts. The results establish that depressive and anxious symptoms were significantly related to norepinephrine and platelet activation in response to acute stress among caregivers but not among non-caregivers. Methodological findings support the validity of the acute stress test as a tool for provoking platelet activation in longitudinal designs. The combined influence of hormone replacement therapy and caregiving stress was associated with prolonged platelet activation among post-menopausal women. Persistent assessments of negative affect bore stronger and more consistent relationships to platelet activity than transient assessments. In sum, exaggerated platelet activation in response to stress, affect, or pharmacological risk may contribute to the development or evolution of cardiovascular disease processes, under conditions of chronic stress such as caregiving.