Elsevier

Autonomic Neuroscience

Volume 207, November 2017, Pages 2-9
Autonomic Neuroscience

Cardiovascular and autonomic reactivity to psychological stress: Neurophysiological substrates and links to cardiovascular disease

https://doi.org/10.1016/j.autneu.2017.03.003Get rights and content

Highlights

  • Cardiovascular reactions to stress may confer CVD risk.

  • Brain circuits for autonomic control generate and regulate cardiovascular stress reactions.

  • These circuits may be important for linking stress to CVD.

Abstract

Psychologically stressful experiences evoke changes in cardiovascular physiology that may influence risk for cardiovascular disease (CVD). But what are the neural circuits and intermediate physiological pathways that link stressful experiences to cardiovascular changes that might in turn confer disease risk? This question is important because it has broader implications for our understanding of the neurophysiological pathways that link stressful and other psychological experiences to physical health. This review highlights selected findings from brain imaging studies of stressor-evoked cardiovascular reactivity and CVD risk. Converging evidence across these studies complements animal models and patient lesion studies to suggest that a network of cortical, limbic, and brainstem areas for central autonomic and physiological control are important for generating and regulating stressor-evoked cardiovascular reactivity via visceromotor and viscerosensory mechanisms. Emerging evidence further suggests that these brain areas may play a role in stress-related CVD risk, specifically by their involvement in mediating metabolically-dysregulated or extreme stressor-evoked cardiovascular reactions. Contextually, the research reviewed here offers an example of how brain imaging and health neuroscience methods can be integrated to address open and mechanistic questions about the neurophysiological pathways linking psychological stress and physical health.

Introduction

How do stress-related processes instantiated in the brain relate to an individual's risk for atherosclerotic cardiovascular disease (CVD) and related adverse cardiovascular outcomes that continue to be leading burdens to public health (Mozaffarian et al., 2016)? Addressing this open question is important: it has the potential to (i) advance our mechanistic understanding of the human neurophysiological substrates for psychological and behavioral influences on the development of CVD and (ii) inform novel and brain-based efforts to better predict and possibly reduce CVD risk. Historically, acute cardiovascular reactions (e.g., rapid and autonomically mediated rises in blood pressure [BP] and heart rate [HR]) to psychological stressors have been among the most heavily investigated stress-related parameters of CVD risk. Over the short-term, such stressor-evoked cardiovascular reactions may be adaptive, insofar as they provide hemodynamic and metabolic support for contextually appropriate behaviors that confer survival advantage (e.g., fight-or-flight behaviors). Over the long-term, however, stressor-evoked cardiovascular reactions that are exaggerated, prolonged, and repeatedly expressed may initiate or exacerbate pathophysiological changes in the heart and vasculature. More precisely, there is longstanding and cumulative epidemiological evidence that individuals who exhibit a phenotype characterized by the expression of large-magnitude or metabolically-exaggerated stressor-evoked cardiovascular reactions are at elevated risk for clinical and preclinical endpoints of CVD (for reviews, see Gerin et al., 2000, Chida and Steptoe, 2010, Taylor et al., 2003, Krantz and Manuck, 1984, Schwartz et al., 2003, Treiber et al., 2003). These endpoints include an accelerated progression of atherosclerosis (e.g., Barnett et al., 1997, Jennings et al., 2004); the premature development of hypertension (e.g., Carroll et al., 2011, Carroll et al., 2012b); increased ventricular mass (e.g., Allen et al., 1997, Georgiades et al., 1996); concentric remodeling of the heart (e.g., al'Absi et al., 2006); future coronary events (e.g, myocardial infarctions) (Schwartz et al., 2003, Treiber et al., 2003); and cardiovascular disease mortality (Carroll et al., 2012a).

The brain has long been implicated in the control of cardiovascular function, particularly in linking stressful experiences to cardiovascular changes associated with clinical events and disease pathophysiology (for reviews see Dampney, 2015, Lane et al., 2009a, Lane et al., 2009b, Palma and Benarroch, 2014, Taggart et al., 2016, Esler, 2017). For example, Cannon originally proposed that intense emotions, such as fright, were generated in the brain and triggered peripheral physiological responses that could end one's life in “voodoo death” (Cannon, 1928, Cannon, 1942). It has also long been known that brain damage and neurological phenomena (e.g., epilepsy, stroke) can result in detrimental effects on circulatory control via the autonomic nervous system, including sudden cardiac death (Colivicchi et al., 2005, Oppenheimer, 2006, Abboud et al., 2006, Tomson et al., 2008, Nagai et al., 2010). It is in this historical and behavioral medicine context that a growing number of brain imaging studies have sought to explicate the neural circuits that are jointly (i) engaged by psychological stressors and (ii) involved in coordinating autonomic and neuroendocrine activity to proximally influence cardiovascular responding. From a health neuroscience perspective (Erickson et al., 2014), a guiding assumption of these brain-imaging studies is that a better understanding of these neural circuits will help define the mechanistic pathways by which psychological stress may confer CVD risk and result in adverse clinical events. The goal of this brief review is to highlight key and convergent findings from these studies, as well as describe salient methodological issues, interpretive caveats, and future directions inherent to brain-imaging studies of cardiovascular reactivity and CVD risk.

Section snippets

Stressor-evoked cardiovascular reactivity and CVD

Psychological stressors can be defined as perceived threats to well-being that tax or exceed an individual's capacity to cope with such threats (Lazarus, 1966). Individuals differ appreciably, however, in the extent to which they ascribe threat-related and psychological meaning to events, contexts, and myriad other stimuli. They also differ in the extent to which they construe their available coping resources and options as adequate for managing potential sources of threat. These individual

Brain-imaging studies of stressor-evoked cardiovascular reactivity

As detailed in recent meta-analyses and other reviews (e.g., Gianaros and Wager, 2015, Thayer et al., 2012, Myers, 2017, Shoemaker and Goswami, 2015, Beissner et al., 2013, Muscatell and Eisenberger, 2012), functional divisions of the anterior cingulate cortex (ACC) and adjacent medial prefrontal cortex (mPFC), insula, hippocampus, and amygdala may be viewed as a core – albeit not exclusive – components of a broader network of forebrain systems involved in mediating stressor-evoked changes in

Central visceral control mechanisms for stressor-evoked cardiovascular reactivity

As noted earlier, changes in BP and HR are reliably evoked by psychological stressors, and these stressor-evoked cardiovascular changes have long been linked to CVD risk. BP itself is a circulatory parameter that is under the control of the baroreflex. The baroreflex constrains beat-to-beat variation in BP by adjusting sympathetic and parasympathetic outflow to the heart and vasculature to alter heart rate and vessel tone, and hence cardiac output and peripheral resistance. Rises in BP distort

Conclusions

The neurophysiological or ‘brain-body’ pathways linking psychological stress and CVD risk still remain largely uncertain (Lovallo, 2005, Lane et al., 2009a, Lane et al., 2009b). Arguably, delineating these pathways may not only aid in developing brain-based strategies for augmenting CVD risk stratification and prediction in the emerging field of neurocardiology (Shivkumar et al., 2016, Silvani et al., 2016), but also in furthering a mechanistic understanding of stress-related processes

Acknowledgements/funding

The authors would like to acknowledge the following funding sources: National Institutes of Health Grants T32 HL07560 and R01 HL089850.

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