Does altered glucocorticoid homeostasis increase cardiovascular risk?

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular effects of chronic sympathetic and RAA activation are well recognized, illustrating that the short-term benefit of the physiologic stress response can be detrimental in the long term. Similarly, chronic tissue exposure to glucocorticoids may lead to metabolic and vascular changes that accelerate vascular senescence. Specific situations associated with chronic activation of the HPA axis-such as major depression, inflammatory disease and perhaps the metabolic syndrome-may derive some of their associated cardiovascular risk from untoward glucocorticoid effects. Since there are no definitive clinical studies directly addressing the relationship between the HPA axis and cardiovascular disease, we present indirect evidence from two types of studies: (1) studies that examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies demonstrating that endogenous glucocorticoid activity varies between individuals. The effects of physiologic increases in endogenous glucocorticoid activity may not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless, the known effects of exogenous glucocorticoids provide important insights into the putative effects of endogenous glucocorticoids.

Inequities in CHD Incidence and Case Fatality by Neighborhood Deprivation

“…Normative values, psychological stress (such as that due to discrimination and/or violence), depression, or chronic infections may be other contributory factors for future studies to explore. [36][37][38][39][40][41][42] Neighborhood-level inequities may also manifest via unequal access to and quality of primary and secondary healthcare services, discrimination in the access or delivery of care, different compliance with medications, and/or other healthcare-related factors, even in countries with universal access to medical care and smaller income-related inequalities in health than in other countries. 11,43 In Sweden, medical care coverage is provided to all permanent residents, and primary healthcare clinics and hospitals are equally distributed and located in central areas in all types of neighborhoods.…”

Higher overcommitment to work is associated with higher plasma cortisol but not ACTH responses in the combined dexamethasone/CRH test in apparently healthy men and women

“…Elevated hormonal responses to the dex/CRH test in depression have been proposed to reflect impaired glucocorticoid functioning, a key mechanism in the pathogenesis of depression (Ising et al, 2005) that might at least in part underlie the increased CHD risk with depression (Girod and Brotman, 2004;Lett et al, 2004;Parissis et al, 2007). However, to date it is not known whether elevated hormonal responses to the dex/CRH test as observed in depression can be observed in other independent psychological risk factors for CHD such as OC.…”

Glucocorticoids and cardiovascular events in rheumatoid arthritis: A population‐based cohort study

“…The role of glucocorticoids in the occurrence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) has been a subject of controversy for decades (1)(2)(3)(4)(5)(6). The undesirable effects of glucocorticoids on blood pressure, insulin resistance, lipid profile, body weight and fat distribution, and coagulation proteins might significantly increase the risk of CVD in RA patients (1,2,4,6).…”

“…The undesirable effects of glucocorticoids on blood pressure, insulin resistance, lipid profile, body weight and fat distribution, and coagulation proteins might significantly increase the risk of CVD in RA patients (1,2,4,6). Although the literature supports the development of these potentially harmful effects with high-dose glucocorticoid therapy, it has been recognized that there is no firm evidence linking low-dose therapy and CVD in the RA population (7,8).…”