Ronaldson, AL; (2017) Psychosocial stress and cardiovascular disease: The role of the hypothalamic-pituitary-adrenal axis. Doctoral thesis , UCL (University College London).

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Abstract

There is evidence to suggest that dysregulation of the HPA axis might be one of the biological pathways linking psychosocial stress with cardiovascular disease (CVD). This PhD consisted of three studies that aimed to assess the role of HPA axis dysregulation in CVD, and to examine potential biological mechanisms that might be involved in stress-related HPA axis dysregulation. Study 1 assessed the utility of pre-surgical diurnal cortisol rhythm in predicting adverse outcomes in advanced heart disease using data from an observational clinical cohort study. The results showed that patients with flatter pre-surgical cortisol slopes were at increased risk of experiencing an adverse event in the years following coronary revascularisation. This finding provides evidence for the clinical relevance of HPA axis dysregulation in CVD. Study 2 and 3 sought to garner more information about the biological mechanisms underlying stress-related HPA axis dysregulation using data from a randomised controlled trial involving the administration of pharmacological probes to healthy volunteers. In Study 2 the effects of six-day administration of beta-blockers and SSRIs on diurnal cortisol secretion were examined. Results indicated that women taking SSRIs had significantly steeper diurnal cortisol slopes compared to placebo. Mechanistically, these results support the notion that the serotonergic system exerts substantial effects on the HPA axis, potentially through modulation of the serotonergic or corticosteroid receptors. Therapeutically, these results suggest that SSRIs might be a plausible intervention for female CHD patients with flatter cortisol slopes In Study 3 the effects of seven-day administration of beta-blockers and SSRIs on cortisol stress reactivity and corticosteroid receptor sensitivity in the laboratory were investigated. The results indicated that generally, acute stress brought about a decrease in corticosteroid receptor sensitivity. SSRIs enhanced this decrease and also blunted the cortisol stress response. These results suggest that SSRIs may enhance adaptive stress-related changes in HPA axis function, thereby having therapeutic implications for stress-related illness such as CVD. Together this body of work indicates that alterations in HPA axis function play a role in CVD and that the serotonergic system likely plays a role in stress-related dysregulation of the HPA axis.

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