A cornerstone for research into the link between stress and health has been the reactivity hypothesis; cardiovascular reactivity to psychological stressors, if prolonged or exaggerated, can promote the development of cardiovascular disease. However, it has recently been argued that low or blunted reactivity is also associated with negative health outcomes. As such, in this special issue we present further evidence implicating that cardiovascular and stress hormone responses to acute stress at the other end of the response spectrum can also be considered a pathway to ill health. In this introductory article, we explore and review the origins of and potential mechanisms underlying blunted responses to acute stress. In so doing, we aim to highlight: what is currently known regarding this new conceptualization of the reactivity hypothesis; the potential explanations for blunted reactivity; the pathways underlying associations with health outcomes; and where this field is headed in terms of developing our understanding of the link between reactivity and health.

Recent research shows that blunted cardiovascular and cortisol reactions to acute psychological stress are associated with adverse behavioural and health outcomes: depression, obesity, bulimia, and addictions. These outcomes may reflect suboptimal functioning of the brain's fronto-limbic systems that are needed to regulate motivated behaviour in the face of challenge. In support of this, brain imaging data demonstrate fronto-limbic hypoactivation during acute stress exposure. Those demonstrating blunted reactions also show impairments of motivation, including lower cognitive ability, more rapid cognitive decline, and poorer performance on motivation-dependent tests of lung function. Persons exhibiting blunted stress reactivity display well established temperament characteristics, including neuroticism and impulsivity, characteristic of various behavioural disorders. Notably, the outcomes related to blunted stress reactivity are similar to those that define Reward Deficiency Syndrome. Accordingly, some individuals may be characterised by a broad failure in cardiovascular and cortisol responding to both stress and reward, reflecting fronto-limbic dysregulation. Finally, we proffer a model of blunted stress reactivity, its antecedents and sequelae, and identify future research priorities.

BackgroundThere is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22–23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers.DiscussionHere we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function.SummaryWe present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological studies of human ageing, in health surveys of older people and as outcomes in intervention studies that aim to promote healthy ageing. Further, the inclusion of the same common panel of measures of healthy ageing in diverse study designs and populations may enhance the value of those studies by allowing the harmonisation of surrogate endpoints or outcome measures, thus facilitating less equivocal comparisons between studies and the pooling of data across studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0470-9) contains supplementary material, which is available to authorized users.

Exaggerated cardiovascular reactions to acute psychological stress may be involved in the etiology of cardiovascular pathology. The present analysis examined the association between the magnitude of systolic and diastolic blood pressure reactions to stress and cardiovascular disease mortality. Participants were 431 (229 women) from the West of Scotland Twenty‐07 Study, aged 63 years at the time of stress testing, where blood pressure was measured during resting baseline and mental arithmetic stress. Participants' vital status was tracked for the next 16 years, during which time 38 had died of cardiovascular disease. Both systolic and diastolic blood pressure reactions were positively associated with cardiovascular disease mortality. This association could reflect the long‐term erosive effects of exaggerated reactivity on the vasculature as well as its short‐term capacity to trigger acute cardiovascular events.

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The aim of this study is to examine the association between symptoms of depression and anxiety and hypertension status. Participants (n=455, 238 women) were drawn from the Dutch Famine Birth Cohort Study. In 2002-2004, they attended a clinic assessment during which socio-demographics, anthropometrics, resting systolic blood pressure (SBP) and health behaviours were measured. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale. In 2008-2009, participants completed a questionnaire, which asked whether they ever had a physician diagnosing them as suffering from hypertension. In separate regression models that initially adjusted for age and then additionally for sex, socio-economic status, smoking, sports participation, alcohol consumption, resting SBP, antidepressive and anxiolytic medication, whether or not participants were exposed to the Dutch famine in utero, BMI and waist:hip ratio, both depression and anxiety were positively associated with hypertension status. Those who met the criterion for possible clinical depression and anxiety were also more likely to be hypertensive, and these associations remained statistically significant in the fully adjusted regression model. In conclusion, symptoms of depression and anxiety were associated with a diagnosis of hypertension assessed 5 years later, although the mechanisms underlying these associations remain to be determined.

A series of meta-analyses was undertaken to determine the contributions of sympathetic and parasympathetic activation to cardiovascular stress reactivity. A literature search yielded 186 studies of sufficient quality that measured indices of sympathetic (n = 113) and/or parasympathetic activity (n = 73). A range of psychological stressors perturbed blood pressure and heart rate. There were comparable aggregate effects for sympathetic activation, as indexed by increased plasma epinephrine and norepinephrine, and shortened pre-ejection period and parasympathetic deactivation, as indexed by heart rate variability measures. Effect sizes varied with stress task, sex, and age. In contrast to alpha-adrenergic blockade, beta-blockade attenuated cardiovascular reactivity. Cardiovascular reactivity to acute psychological stress would appear to reflect both beta-adrenergic activation and vagal withdrawal to a largely equal extent.

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.