Mental Stress and Its Effects on Vascular Health

Abstract

Coronary artery disease continues to be a major cause of morbidity and mortality despite significant advances in risk stratification and management. This has prompted the search for alternative nonconventional risk factors that may provide novel therapeutic targets. Psychosocial stress, or mental stress, has emerged as an important risk factor implicated in a higher incidence of cardiovascular events, and although our understanding of this far ranging and interesting phenomenon has developed greatly over recent times, there is still much to be learned regarding how to measure mental stress and how it may impact physical health. With the current coronavirus disease 2019 global pandemic and its incumbent lockdowns and social distancing, understanding the potentially harmful biological effects of stress related to life-changing events and social isolation has become even more important. In the current review our multidisciplinary team discusses stress from a psychosocial perspective and aims to define psychological stress as rigorously as possible; discuss the pathophysiologic mechanisms by which stress may mediate cardiovascular disease, with a particular focus to its effects on vascular health; outline existing methods and approaches to quantify stress by means of a vascular biomarker; outline the mechanisms whereby psychosocial stressors may have their pathologic effects ultimately transduced to the vasculature through the neuroendocrine immunologic axis; highlight areas for improvement to refine existing approaches in clinical research when studying the consequences of psychological stress on cardiovascular health; and discuss evidence-based therapies directed at reducing the deleterious effects of mental stress including those that target endothelial dysfunction. To this end we searched PubMed and Google Scholar to identify studies evaluating the relationship between mental or psychosocial stress and cardiovascular disease with a particular focus on vascular health. Search terms included "myocardial ischemia," "coronary artery disease," "mental stress," "psychological stress," "mental∗ stress∗," "psychologic∗ stress∗," and "cardiovascular disease∗." The search was limited to studies published in English in peer-reviewed journals between 1990 and the present day. To identify potential studies not captured by our database search strategy, we also searched studies listed in the bibliography of relevant publications and reviews.

Figure 1

Schematic outline of the relationship between acute and chronic stressors and stress defined as the individual response to challenge, stress’s dynamic interaction with extraneous bio-psycho-social factors, and beneficial and pathologic consequences of stress.

Figure 2

Outline of the various mechanisms by which stress pathologically affects vascular health (in boxes), and biomarkers available to measure these effects. CBF, coronary blood flow; CRP, C-reactive protein; DBP, diastolic blood pressure; FMD, flow-mediated dilatation; H-P-A axis, hypothalamic-pituitary-adrenal axis; HR, heart rate; IL, interleukin; LV, left ventricular; MS, mental stress; MSIMI, mental stress induced myocardial ischemia; NF-κβ; nuclear factor kappa light chain enhancer of activated B cells; PP, pulse pressure; RH-PAT, reactive hyperemia – peripheral arterial tonometry; SBP, systolic blood pressure; SVR, systemic vascular resistance; TNF, tumor necrosis factor.

Figure 3

Outline of how mental stress (MS) leads to microvascular and macrovascular endothelial dysfunction (ED), how each of these can lead to pathologic and clinical manifestations of cardiovascular (CV) disease that can be measured, and how ED could be used as a diagnostic and therapeutic target when managing MS and its associated risk of CV disease. CIMT, carotid intima media thickness; PAT, peripheral arterial tonometry; RH-PAT, reactive hyperemia–peripheral arterial tonometry.