Annie T. Ginty

The other side of the coin: Blunted cardiovascular and cortisol reactivity are associated with negative health outcomes

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.

Disordered eating behaviour is associated with blunted cortisol and cardiovascular reactions to acute psychological stress

Research suggests a potential dysregulation of the stress response in individuals with bulimia nervosa. This study measured both cardiovascular and cortisol reactions to a standardised laboratory stress task in individuals identified as showing disordered eating behaviour to determine whether dysregulation of the stress response is characteristic of the two branches of the stress response system. Female students (N=455) were screened using two validated eating disorder questionnaires. Twelve women with disordered eating, including self-induced vomiting, and 12 healthy controls were selected for laboratory stress testing. Salivary cortisol and cardiovascular activity, via Doppler imaging and semi-automatic blood pressure monitoring, were measured at resting baseline and during and after exposure to a 10-min mental arithmetic stress task. Compared to controls the disordered eating group showed blunted cortisol, cardiac output, heart rate, and stroke volume reactions to the acute stress, as well as an attenuated vasodilatory reaction. These effects could not be accounted for in terms of group differences in stress task performance, subjective task impact/engagement, age, BMI, neuroticism, cardio-respiratory fitness, or co-morbid exercise dependence. Our findings suggest that disordered eating is characterised by a dysregulation of the autonomic stress-response system. As such, they add further weight to the general contention that blunted stress reactivity is characteristic of a number of maladaptive behaviours and states.

A proposed panel of biomarkers of healthy ageing

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.

Preliminary evidence that exercise dependence is associated with blunted cardiac and cortisol reactions to acute psychological stress

Low or blunted cardiovascular and cortisol reactions to acute psychological stress have been shown to characterise those with a tobacco or alcohol dependency. The present study tested the hypothesis that exercise dependency would be similarly associated with blunted reactivity. Young female exercisers (N=219) were screened by questionnaire for exercise dependence. Ten women with probable exercise dependence and 10 non dependent controls were selected for laboratory stress testing. Cardiovascular activity and salivary cortisol were measured at rest and in response to a 10-min mental arithmetic stress task. The exercise dependent women showed blunted cardiac reactions to the stress task and blunted cortisol at 10, 20, and 30 minute post stress exposure. These effects could not be accounted for in terms of group differences in stress task performance, nor could the cardiac effects be attributed to group differences in cardio-respiratory fitness. It would seem that low stress reactivity is characteristic of a wide range of dependencies, and is not confined to substance dependence. Our results offer further support for the hypothesis that blunted stress reactivity may be a peripheral marker of a central motivational dysregulation.

Blunted cardiac stress reactivity relates to neural hypoactivation

The present study compared neural activity in participants with blunted (N = 9) or exaggerated (N = 8) cardiac stress reactions. Neural activity was recorded with fMRI while participants performed a validated stress task and control task. Exaggerated reactors exhibited significant increases in heart rate from control to stress task, whereas blunted reactors had no change in heart rate. Blunted reactors also had reduced activation in the anterior midcingulate cortex and insula compared to exaggerated reactors during the stress condition, and a greater deactivation in the amygdala and posterior cingulate. The biological differences between groups in response to the stress task could not be explained by subjective measures of engagement, stressfulness, or difficulty. This study supports the notion that blunted peripheral physiological stress reactivity may be a marker of a corresponding under-recruitment of brain systems during behavioral states requiring motivated action.

Systolic blood pressure reactions to acute stress are associated with future hypertension status in the Dutch Famine Birth Cohort Study

These analyses examined the association between blood pressure reactions to acute psychological stress and subsequent hypertension status in a substantial Dutch cohort. Blood pressure was recorded during a resting baseline and during three acute stress tasks, Stroop colour word, mirror tracing and speech. Five years later, diagnosed hypertension status was determined by questionnaire. Participants were 453 (237 women) members of the Dutch Famine Birth Cohort. In analysis adjusting for a number of potential confounders, systolic blood pressure reactivity was positively related to future hypertension. This was the case irrespective of whether reactivity was calculated as the peak or the average response to the stress tasks. The association was strongest for reactions to the speech and Stroop tasks. Diastolic blood pressure reactivity was not significantly associated with hypertension. The results provide support for the reactivity hypothesis.

A tale of two mechanisms: A meta‐analytic approach toward understanding the autonomic basis of cardiovascular reactivity to acute psychological stress

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.

Depression and anxiety are associated with a diagnosis of hypertension 5 years later in a cohort of late middle-aged men and women.

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.

Cardiovascular and cortisol reactions to acute psychological stress and cognitive ability in the Dutch Famine Birth Cohort Study

Given evidence linking blunted cardiovascular and cortisol reactions to acute stress and a range of adverse behavioral outcomes, the present study examined the associations between cardiovascular and cortisol reactivity and cognitive ability measured independently of the stress task exposure. Cognitive ability was assessed using the Alice Heim-4 test of general intelligence and two memory tasks in 724 men and women who were part of the Dutch Famine Birth Cohort Study. Blood pressure and heart rate, as well as cortisol reactivity, were measured to a battery of three standard acute stress tasks. Poorer cognitive ability was associated with lower cardiovascular reactions to stress and lower cortisol area under the curve. Our results are consistent with recent findings implicating low physiological stress reactivity in a range of adverse behavioral and health outcomes.

Cognitive ability and simple reaction time predict cardiac reactivity in the West of Scotland Twenty‐07 Study

Few studies have examined the association between cognitive ability and cardiovascular reactivity, although both have been implicated in later cardiovascular disease. We studied the relationship between cognitive ability, assessed using the Alice Heim-4 test of general intelligence, simple reaction time, and subsequent cardiovascular reactivity in 409 55-year-olds. Blood pressure and heart rate reactions to an acute mental arithmetic task were measured 7 years after cognitive assessment. In regression models that adjusted for baseline cardiovascular activity, socio-demographics, body mass index, medication status, and stress task performance, cognitive ability and reaction time were associated with future cardiac reactivity. Low reactivity was characteristic of those with relatively low cognitive ability. The results are consistent with the notion that high reactivity may not always be a maladaptive response.