By what molecular mechanisms do social determinants impact cardiometabolic risk?

Abstract

While it is well known from numerous epidemiologic investigations that social determinants (socioeconomic, environmental, and psychosocial factors exposed to over the life-course) can dramatically impact cardiovascular health, the molecular mechanisms by which social determinants lead to poor cardiometabolic outcomes are not well understood. This review comprehensively summarizes a variety of current topics surrounding the biological effects of adverse social determinants (i.e., the biology of adversity), linking translational and laboratory studies with epidemiologic findings. With a strong focus on the biological effects of chronic stress, we highlight an array of studies on molecular and immunological signaling in the context of social determinants of health (SDoH). The main topics covered include biomarkers of sympathetic nervous system and hypothalamic–pituitary–adrenal axis activation, and the role of inflammation in the biology of adversity focusing on glucocorticoid resistance and key inflammatory cytokines linked to psychosocial and environmental stressors (PSES). We then further discuss the effect of SDoH on immune cell distribution and characterization by subset, receptor expression, and function. Lastly, we describe epigenetic regulation of the chronic stress response and effects of SDoH on telomere length and aging. Ultimately, we highlight critical knowledge gaps for future research as we strive to develop more targeted interventions that account for SDoH to improve cardiometabolic health for at-risk, vulnerable populations.

Neighborhood socioeconomic deprivation and individual-level socioeconomic status are associated with dopamine-mediated changes to monocyte subset CCR2 expression via a cAMP-dependent pathway

“…The increased CCR2 levels induced by DA, especially on NCM, in our study support a differential effect of DA on NCM and, possibly, accelerated monocyte migration. These results underscore the importance of continued investigation into monocyte signaling in response to DA ( Baumer et al, 2023 ).…”

“…Investigations into how chronic stress may mediate the relationship between socioeconomic disparities and CVD have recently garnered increased attention ( Tawakol et al, 2019 ; Miller et al, 2019 ; Powell-Wiley et al, 2021 ). Specifically, associations have been found between NSD as well as individual level socioeconomic status (SES) and different pathophysiological features altered by chronic stress ( Baumer et al, 2023 ) including cortisol levels or reactivity ( Barrington et al, 2014 ; Miller et al, 2009 ), telomere length ( Powell-Wiley et al, 2020 ; Alexeeff et al, 2019 ), and chronic stress-related neural activity as measured by amygdala activity in 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) ( Tawakol et al, 2019 ; Powell-Wiley et al, 2021 ). The measurement of amygdala activity has emerged as a powerful tool to assess stress given the instrumental role of the amygdala in the stress response.…”

sSocial Determinants of Health and Cumulative Incidence of Mortality among U.S. Adults without Major Chronic Diseases

“…4–7 SDOH are hypothesized to act, at least partially, via epigenetic, inflammatory, or hormonal pathways to impact health negatively. 4,8–10…”

“…[4][5][6][7] SDOH are hypothesized to act, at least partially, via epigenetic, inflammatory, or hormonal pathways to impact health negatively. 4,[8][9][10] While SDOH has been shown to exacerbate numerous chronic diseases, relatively little is known about how SDOH impacts the prognosis of healthy adults. Understanding the role of adverse SDOH in determining risk for poor outcomes in states of apparent health may provide valuable insights into preventative health strategies upstream of the healthcare system.…”

Social Determinants of Health in Cardio-Oncology

“… 1 For instance, prolonged exposure to adverse SDOH is directly associated with the development of CVD risk factors and poor cardiovascular health behaviors (ie, smoking, physical inactivity, low-quality dietary intake, and poor sleep quality). Moreover, chronic psychosocial and environmental stressors related to adverse SDOH trigger biologic pathways, 2 such as activation of the sympathetic nervous system, the hypothalamic-pituitary-adrenal axis, and the neural-hematopoietic axis, to create a proinflammatory milieu that promotes cancer, 3 diabetes mellitus, 4 and CVD. 5 …”