Stress and cardiovascular disease: an update

Abstract

Psychological stress is generally accepted to be associated with an increased risk of cardiovascular disease (CVD), but results have varied in terms of how stress is measured and the strength of the association. Additionally, the mechanisms and potential causal links have remained speculative despite decades of research. The physiological responses to stress are well characterized, but their contribution to the development and progression of CVD has received little attention in empirical studies. Evidence suggests that physiological responses to stress have a fundamental role in the risk of CVD and that haemodynamic, vascular and immune perturbations triggered by stress are especially implicated. Stress response physiology is regulated by the corticolimbic regions of the brain, which have outputs to the autonomic nervous system. Variation in these regulatory pathways might explain interindividual differences in vulnerability to stress. Dynamic perturbations in autonomic, immune and vascular functions are probably also implicated as CVD risk mechanisms of chronic, recurring and cumulative stressful exposures, but more data are needed from prospective studies and from assessments in real-life situations. Psychological assessment remains insufficiently recognized in clinical care and prevention. Although stress-reduction interventions might mitigate perceived stress levels and potentially reduce cardiovascular risk, more data from randomized trials are needed.

Fig. 1 |. Mechanistic model linking psychological stress and CVD.

Chronic stressors cause dysregulation of adaptive stress response systems by acting on specific brain areas that are part of the corticolimbic system, which are also implicated in the development of stress-related mental health conditions. These brain regions, in turn, regulate neuroendocrine and autonomic response systems. The latter influence peripheral vascular, immune and haemodynamic physiology. These effects can be chronic but can be exacerbated by dynamic perturbations during everyday acute stressors as well as by mental health comorbidities such as depression and post-traumatic stress disorder (PTSD). Ultimately, these pathways can cause atherosclerotic plaque disruption, myocardial ischaemia, atherothrombosis and cardiac arrhythmias, especially among individuals with a high risk of cardiovascular disease (CVD), leading to acute coronary events. However, the effects of stress vary between individuals and population groups. These differences might reside in variations in stress response physiology and in the molecular pathways connecting peripheral stress responses to the risk of CVD.

Fig. 2 |. Cumulative incidence of cardiovascular disease end points for separate myocardial ischaemia phenotypes.

The graph shows the incidence of cardiovascular death or non-fatal myocardial infarction (MI) during a median follow-up of 5 years, classified according to the type of stress test used to induced myocardial ischaemia, in 899 individuals with coronary heart disease. Myocardial ischaemia induced by mental stress, conventional stress or both was assessed at baseline with single-photon emission computed tomography myocardial perfusion imaging. Mental stress was induced in the laboratory using a speech task that included elements of social–evaluative threat. Conventional stress testing was performed using either an exercise stress test or a pharmacological stress test on a separate day within 1 week from the mental stress. Reprinted with permission from ref. , JAMA.

Fig. 3 |. The central role of stress response physiology in cardiovascular risk secondary to psychological stress.

The medial prefrontal cortex and other regions of the corticolimbic systems have a pivotal role in the regulation of both emotional and physiological responses to stress. Physiological responses to stress that have a demonstrated connection with cardiovascular disease (CVD) events in prospective studies include haemodynamic, ischaemic, vagal, vascular and inflammatory responses to stress. Most of these physiological responses have also been linked to specific brain activation patterns in brain imaging studies of acute mental stress.