Disentangling the Links Between Psychosocial Stress and Cardiovascular Disease

Abstract

Stress is a pervasive component of the human experience. While often considered an adversity to be ignored, chronic stress has important pathological consequences, including cardiovascular disease (CVD). Stress also increases the prevalence and severity of several CVD risk factors, including hypertension, diabetes mellitus, and obesity. Yet even after adjustment, stress' attributable CVD risk is similar to those risk factors, suggesting it is a particularly potent contributor. Nevertheless, there has been insufficient study of mechanisms linking stress to CVD or of methods to attenuate stress' pathological impact. This review covers the current concepts of how stress impacts CVD and emerging approaches to mitigate stress-attributable CVD risk.

Keywords: atherosclerosis; cardiovascular diseases; humans; hypertension; psychological distress; risk adjustment; risk factors.

Figure 1:

Glossary of Terms and Abbreviations Commonly used terms (A) and abbreviations (B) are defined.

Figure 2:

Stress and CVD Risk The international INTERHEART study showed that psychosocial stress associates with a heightened CVD risk across ethnic groups (A), and the attributable risk is similar to that of major CVD risk factors (B). Reused with permission.^,

Figure 3:

Physiological Consequences of Stress Chronic stress triggers several disease-promoting physiological changes, including: HPA axis activation, behavioral and cardiometabolic changes, increased SNS and decreased PSNS activity, heightened leukopoiesis, and immune dysregulation. ACTH-adrenocorticotropic hormone, CRF-corticotropin-releasing factor, HPA-hypothalamic-pituitary-adrenal, NE-norepinephrine, SNS and PNS-sympathetic and parasympathetic nervous systems, respectively.

Figure 4:

Multi-System Imaging of Tissue Biology Advanced imaging using ¹⁸F-Fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (¹⁸F-FDG-PET/MRI) provides a unique opportunity to measure stress-associated neurobiology as it relates to cardiovascular disease. Multiparametric-multi-tissue imaging can be obtained in a single session. MRI data include measurements of neural structures (A), stressor-stimulated neural activation and connectivity using functional MRI (B), and structural cardiovascular measures (C). ¹⁸F-FDG-PET/MRI is used to image resting neurobiological metabolic activity (D), leukopoietic activity (E) and arterial inflammation (F). Red solid arrow=carotid artery, red hatched arrows=aorta, white solid arrows=amygdalar activity, white hatched arrows=bone marrow.

Figure 5:

Mechanisms Linking Stress to CVD Chronic stress upregulates stress-associated neurobiological activity, leading to increased CVD risk factors (e.g., obesity, hypertension, and insulin resistance) and heightened inflammation via a neural-immune axis. This in turn drives increased arterial inflammation and non-calcified coronary plaque burden, resulting in higher CVD risk independent of traditional risk factors. BM-bone marrow, CVD-cardiovascular disease, HTN-hypertension, SNS-sympathetic nervous system, HPA-hypothalamic-pituitary-adrenal.

Figure 6:

Socioeconomic and Environmental Stressors vs. Stress-Associated Neurobiological Activity and CVD Events. Individuals were categorized according to quartiles of neighborhood median income and transportation noise exposure. Amygdalar activity decreased as neighborhood median income increased (A) and increased as transportation noise exposure increased (B). Error bars represent standard error of the mean. Similarly, CVD event-free survival was lower among individuals with lower neighborhood income (C) or higher chronic noise exposure (D, >55 dBA, a level deemed unhealthy by the World Health Organization). Reused with permission.^, MACE-major adverse cardiovascular event.

Figure 7:

Impact of Stress Reduction on CVD Events Individuals randomized to cardiac rehabilitation (CR) plus stress management training (SMT) had fewer CVD events versus CR-alone (18% vs. 33%, HR [95% CI]=0.49 [0.25, 0.95], p=0.035,*), and both CR groups had lower event rates versus the No-CR group (47%, HR [95% CI]=0.44 [0.27, 0.71], p<0.001). Reused with permission. CI-confidence interval, HR-hazard ratio.