Increased daytime and awakening salivary free aldosterone in essential hypertensive men.

Background: While aldosterone plays an important role in blood pressure regulation, its role in essential hypertension (EHT) remains unclear. Here, we systematically investigated the secretion of biologically-active free aldosterone in saliva in response to awakening (AldAR) and during the day (AldDay) in EHT compared to normotensive controls (NT). Methods: In 30 men with EHT and 30 age-matched NT, AldAR saliva samples were collected immediately after awakening and 15, 30, 45, and 60 min thereafter and AldDay samples were collected from 08:30-22:00 h on two consecutive days. Results: Over the course of the day, men with EHT had higher repeated AldDay levels compared to NT (p = .002) with higher concentrations in the morning hours (p's ≤ .047), a steeper decline over the course of the day (p's ≤ .018), and similar concentrations in the evening (p's ≥ .21). Regarding AldAR, we observed higher concentrations in EHT at awakening (p = .017) and borderline higher concentrations at 15 min (p = .086). No differences were found 30-60 min after awakening (p's ≥ .34). Analyses with repeated and aggregated AldAR levels resulted in borderline significantly higher free aldosterone in EHT (p's ≤ .077). Complementary analyses confirmed linear associations between higher blood pressure and higher AldAR and AldDay levels. Conclusions: Our data point to elevated salivary free aldosterone secretion in EHT over the course of the day, particularly in the morning hours. As the free aldosterone fraction is considered biologically active, our data may point to a biological mechanism underlying EHT.

Stress in the collective: Psychophysiological reactivity to an orchestra concert as a collective naturalistic, real-life stressor of psychosocial nature.

BACKGROUND & OBJECTIVES: The investigation of collective stress experiences, including collective stressors and the psychophysiological reactivity of a collective to these stressors, has been widely neglected so far. Here, we examined public non-professional orchestra concerts as collective naturalistic, real-life stressors of psychosocial nature and the resulting psychophysiological reactivity in a collective of non-professional orchestra musicians. METHODS: The members of two non-professional music orchestras (N = 54) were accompanied during a public concert (stress condition) and a rehearsal (control condition). We repeatedly assessed heart rate, salivary cortisol, and excitement levels before, during, and after the concert/rehearsal in addition to the anticipatory cognitive stress appraisal. RESULTS: We observed greater physiological reactivity to the concert compared to the rehearsal (p's ≤.017), with higher increases in heart rate levels in anticipation of and in reaction to the concert and in cortisol levels in reaction to the concert compared to the rehearsal. Moreover, orchestra members reported greater psychological reactivity to the concert than to the rehearsal (p's ≤.024) in terms of higher cognitive stress appraisal in anticipation and increased excitement levels before and during the concert compared to the rehearsal. DISCUSSION: Our findings indicate that orchestra concerts by non-professional musicians constitute collective naturalistic, real-life stressors of psychosocial nature, resulting in significant psychophysiological stress responses with reactivity kinetics differing between the sympathetic-adrenal-medullary axis, the hypothalamic-pituitary-adrenal axis, and the psychological response. Potential implications and modulating factors need to be elucidated in future studies.

Taking appreciation to heart: appreciation at work and cardiovascular risk in male employees.

Introduction: While perceived appreciation at work has been associated with self-reported health and wellbeing, studies considering biological health markers are lacking. In this study, we investigated whether appreciation at work would relate to coronary heart disease (CHD) risk as well as the specificity of this proposed association. Methods: Our study comprised a total of 103 male participants, including apparently healthy, medication-free, non-smoking men in the normotensive to hypertensive range (n = 70) as well as medicated hypertensive and CHD patients (n = 33). CHD risk was assessed by blood pressure [mean arterial pressure (MAP)], the diabetes marker glycated hemoglobin A1c (HbA1c), blood lipids [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio], coagulation activity (D-dimer and fibrinogen), and inflammation [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)]. Perceived appreciation at work, as well as potentially confounding psychological factors (social support, self-esteem, and work strain due to a lack of appreciation), were measured by self-report questionnaires. Results: We found higher appreciation at work to relate to lower overall composite CHD risk (p's ≤ 0.011) and, in particular, to lower MAP (p's ≤ 0.007) and lower blood lipids (p's ≤ 0.031) in medication-free participants as well as all participants. This overall association was independent of confounding factors, including related psychological factors (p's ≤ 0.049). Discussion: Our findings indicate that appreciation at work might be an independent health-promoting resource in terms of CHD risk. Implications include that encouraging appreciation at work may help reduce the development and progression of CHD.

Is your stress my stress? A standardized, randomized-controlled paradigm to study physiological stress contagion based on direct stress observation.

BACKGROUND & OBJECTIVES: Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics. METHODS: Healthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 20), (2) observe it ("stress observers", n = 36), or (3) observe a corresponding placebo-stress control condition ("placebo-stress observers", n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone. RESULTS: Stress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p's ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers. DISCUSSION: Extending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated.

Eating After Acute Psychosocial Stress in Healthy Men and Women: Sex Differences and Endocrine Mechanisms.

CONTEXT: Overweight and obesity have become a major health burden with a higher prevalence of obesity in women than in men. Mental stress has been discussed to play a role in this context. OBJECTIVE: We investigated endocrine mechanisms underlying eating after acute psychosocial stress and potential sex differences therein. METHODS: A total of 32 male and 31 female healthy participants underwent the Trier Social Stress Test before they tasted ice cream in a bogus taste test 15 minutes after stress. We repeatedly assessed the stress hormone cortisol and the satiety hormone cholecystokinin (CCK) in saliva as well as perceived hunger before and up to 1 hour after stress. RESULTS: Lower immediate total cortisol stress reactivity predicted higher hunger (Ps ≤ .004), but was not associated with food intake (Ps ≥ .90) or total CCK release (Ps ≥ .84). As compared to men, women ate less after stress (Ps < .001) and had consistently lower levels of hunger (Ps ≤ .024) and cortisol (Ps ≤ .008) as well as a lower immediate total cortisol stress reactivity (Ps = .002). Further, they differed in the kinetics of CCK over the total experimental procedure (Ps ≤ .011), in immediate reaction to stress (Ps ≤ .038), and after eating (Ps ≤ .072), with women's CCK levels continuously decreasing while men's CCK levels were reactive. CONCLUSION: We found evidence for lower immediate total cortisol stress reactivity relating to higher perceived hunger, with lower cortisol levels in women. Unlike in men, CCK levels in women were not reactive to acute stress and eating and decreased continuously. Our results may suggest a higher risk for stress-induced eating in women.

Acceptance criteria for new approach methods in toxicology and human health-relevant life science research - part I.

Every test procedure, scientific and non-scientific, has inherent uncertainties, even when performed according to a standard operating procedure (SOP). In addition, it is prone to errors, defects, and mistakes introduced by operators, laboratory equipment, or materials used. Adherence to an SOP and comprehensive validation of the test method cannot guarantee that each test run produces data within the acceptable range of variability and with the precision and accuracy determined during the method validation. We illustrate here (part I) why controlling the validity of each test run is an important element of experimental design. The definition and application of acceptance criteria (AC) for the validity of test runs is important for the setup and use of test methods, particularly for the use of new approach methods (NAM) in toxicity testing. AC can be used for decision rules on how to handle data, e.g., to accept the data for further use (AC fulfilled) or to reject the data (AC not fulfilled). The adherence to AC has important requirements and consequences that may seem surprising at first sight: (i) AC depend on a test method's objectives, e.g., on the types/concentrations of chemicals tested, the regulatory context, the desired throughput; (ii) AC are applied and documented at each test run, while validation of a method (including the definition of AC) is only performed once; (iii) if AC are altered, then the set of data produced by a method can change. AC, if missing, are the blind spot of quality assurance: Test results may not be reliable and comparable. The establishment and uses of AC will be further detailed in part II of this series.

Physiological reactivity to acute mental stress in essential hypertension-a systematic review.

Objective: Exaggerated physiological reactions to acute mental stress (AMS) are associated with hypertension (development) and have been proposed to play an important role in mediating the cardiovascular disease risk with hypertension. A variety of studies compared physiological reactivity to AMS between essential hypertensive (HT) and normotensive (NT) individuals. However, a systematic review of studies across stress-reactive physiological systems including intermediate biological risk factors for cardiovascular diseases is lacking. Methods: We conducted a systematic literature search (PubMed) for original articles and short reports, published in English language in peer-reviewed journals in November and December 2022. We targeted studies comparing the reactivity between essential HT and NT to AMS in terms of cognitive tasks, public speaking tasks, or the combination of both, in at least one of the predefined stress-reactive physiological systems. Results: We included a total of 58 publications. The majority of studies investigated physiological reactivity to mental stressors of mild or moderate intensity. Whereas HT seem to exhibit increased reactivity in response to mild or moderate AMS only under certain conditions (i.e., in response to mild mental stressors with specific characteristics, in an early hyperkinetic stage of HT, or with respect to certain stress systems), increased physiological reactivity in HT as compared to NT to AMS of strong intensity was observed across all investigated stress-reactive physiological systems. Conclusion: Overall, this systematic review supports the proposed and expected generalized physiological hyperreactivity to AMS with essential hypertension, in particular to strong mental stress. Moreover, we discuss potential underlying mechanisms and highlight open questions for future research of importance for the comprehensive understanding of the observed hyperreactivity to AMS in essential hypertension.

G × E interactions as a basis for toxicological uncertainty.

To transfer toxicological findings from model systems, e.g. animals, to humans, standardized safety factors are applied to account for intra-species and inter-species variabilities. An alternative approach would be to measure and model the actual compound-specific uncertainties. This biological concept assumes that all observed toxicities depend not only on the exposure situation (environment = E), but also on the genetic (G) background of the model (G × E). As a quantitative discipline, toxicology needs to move beyond merely qualitative G × E concepts. Research programs are required that determine the major biological variabilities affecting toxicity and categorize their relative weights and contributions. In a complementary approach, detailed case studies need to explore the role of genetic backgrounds in the adverse effects of defined chemicals. In addition, current understanding of the selection and propagation of adverse outcome pathways (AOP) in different biological environments is very limited. To improve understanding, a particular focus is required on modulatory and counter-regulatory steps. For quantitative approaches to address uncertainties, the concept of "genetic" influence needs a more precise definition. What is usually meant by this term in the context of G × E are the protein functions encoded by the genes. Besides the gene sequence, the regulation of the gene expression and function should also be accounted for. The widened concept of past and present "gene expression" influences is summarized here as Ge. Also, the concept of "environment" needs some re-consideration in situations where exposure timing (Et) is pivotal: prolonged or repeated exposure to the insult (chemical, physical, life style) affects Ge. This implies that it changes the model system. The interaction of Ge with Et might be denoted as Ge × Et. We provide here general explanations and specific examples for this concept and show how it could be applied in the context of New Approach Methodologies (NAM).

Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk.

Background: Coronary heart disease (CHD) and its major risk factor hypertension have both been associated with altered activity of the hypothalamus-pituitary-adrenal (HPA)-axis but the biological mechanisms underlying prospective associations with adverse disease outcomes are unclear. We investigated diurnal HPA-axis activity in CHD-patients, hypertensive (HT) and healthy normotensive men (NT) and tested for prospective associations with biological CHD risk factors. Methods: Eighty-three male CHD-patients, 54 HT and 54 NT men repeatedly measured salivary cortisol over two consecutive days. Prospective CHD risk was assessed by changes between baseline and follow-up in the prothrombotic factors D-dimer and fibrinogen, the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol)/high-density-lipoprotein cholesterol (HDL)-ratio. We aggregated coagulation and inflammatory measures to respective indices. Results: The groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2 p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2 p=.03,f=0.18), with similarly lower overall dayCort and CAR in CHD-patients and HT, as compared to NT. The groups differed further in cortisol at awakening (p=.015,η2 p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2 p=.04,f=0.20) with steepest slopes in HT (p´s≤.039), although in part not independent of confounders. Lower aggregated dayCort and CAR in terms of area-under-the-curve (AUC) independently predicted increases in future overall CHD risk (AUCdayCort: p=.021,η2 p=.10,f=0.33;AUCCAR: p=.028,η2 p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR 2= 0.12;AUCCAR: p=.082). Conclusion: We found evidence for an HPA-axis hypoactivity in CHD and HT with lower diurnal HPA-axis activity predicting increases in cardiovascular risk as evidenced by increases in circulating levels of biomarkers of atherothrombotic risk. Down-regulation of basal HPA-axis activity may contribute to the pathogenesis of atherosclerosis and thrombosis in CHD via effects on coagulation.

Alpha-Adrenergic Mechanisms in the Cardiovascular Hyperreactivity to Norepinephrine-Infusion in Essential Hypertension.

Aims: Essential hypertension (EHT) is characterized by cardiovascular hyperreactivity to stress but underlying mechanism are not fully understood. Here, we investigated the role of α-adrenergic receptors (α-AR) in the cardiovascular reactivity to a norepinephrine (NE)-stress reactivity-mimicking NE-infusion in essential hypertensive individuals (HT) as compared to normotensive individuals (NT). Methods: 24 male HT and 24 male NT participated in three experimental trials on three separate days with a 1-min infusion followed by a 15-min infusion. Trials varied in infusion-substances: placebo saline (Sal)-infusions (trial-1:Sal+Sal), NE-infusion without (trial-2:Sal+NE) or with non-selective α-AR blockade by phentolamine (PHE) (trial-3:PHE+NE). NE-infusion dosage (5µg/ml/min) and duration were chosen to mimic duration and physiological effects of NE-release in reaction to established stress induction protocols. We repeatedly measured systolic (SBP) and diastolic blood pressure (DBP) as well as heart rate before, during, and after infusions. Results: SBP and DBP reactivity to the three infusion-trials differed between HT and NT (p's≤.014). HT exhibited greater BP reactivity to NE-infusion alone compared to NT (trial-2-vs-trial-1: p's≤.033). Group differences in DBP reactivity to NE disappeared with prior PHE blockade (trial-3: p=.26), while SBP reactivity differences remained (trial-3: p=.016). Heart rate reactivity to infusion-trials did not differ between HT and NT (p=.73). Conclusion: Our findings suggest a mediating role of α-AR in DBP hyperreactivity to NE-infusion in EHT. However, in SBP hyperreactivity to NE-infusion in EHT, the functioning of α-AR seems impaired suggesting that the SBP hyperreactivity in hypertension is not mediated by α-AR.

Hyperreactivity of Salivary Alpha-Amylase to Acute Psychosocial Stress and Norepinephrine Infusion in Essential Hypertension.

It is unknown whether the observed general physiological hyperreactivity to acute psychosocial stress in essential hypertension also extends to salivary alpha-amylase (sAA), a surrogate sympathetic nervous system marker. Here, we investigated sAA reactivity to acute psychosocial stress in essential hypertensive males (HT) as compared to normotensive controls (NT). To shed light on underlying mechanisms, we moreover tested for sAA reactivity following a standardized norepinephrine (NE) infusion. We hypothesized that both acute psychosocial stress and an NE infusion of similar duration would lead to greater sAA reactivity in HT than in NT. In the stress study, we examined sAA reactivity to 15 min of acute psychosocial stress induced by the Trier Social Stress Test (TSST) in 19 HT and 23 NT up to 40 min after stress. In the infusion study, 20 HT and 22 NT received a standardized NE infusion (5 µg/mL/min) over 15 min mimicking NE release in reaction to acute psychosocial stress. HT exhibited greater sAA reactivity to the TSST as compared to NT (p = 0.049, ηp2 = 0.08, f = 0.29). In reaction to the standardized NE infusion, HT showed higher sAA reactivity as compared to NT (p = 0.033, ηp2 = 1.00, f = 0.33). Our findings suggest stress-induced sAA hyperreactivity in essential hypertension that seems to be at least in part mediated by a higher reactivity to a standardized amount of NE in HT. With respect to clinical implications, sAA stress reactivity may serve as a noninvasive marker indicative of early cardiovascular risk.

The burden of overweight: Higher body mass index, but not vital exhaustion, is associated with higher DNA damage and lower DNA repair capacity.

BACKGROUND/OBJECTIVES: DNA damage and the capacity to repair damaged DNA have been associated with the pathogenesis of several diseases such as cancer. While it is well known that external mutagenic agents can induce DNA damage, less is known about endogenous contributors to genomic instability. The aim of this study was to investigate whether excess body weight as a physiological factor and vital exhaustion as a psychological factor would be associated with basal levels of DNA damage as well as DNA repair capacity. SUBJECTS/METHODS: In a cross-sectional between-subject design we recruited 53 apparently healthy men within the normal to non-obese overweight range (mean BMI: 25.2 ± 0.5) who were either vitally exhausted (VE) (VE-score ≥ 10) or non-exhausted (VE-score ≤ 3). Vital exhaustion was assessed using the Maastricht Vital Exhaustion Questionnaire. We assessed DNA damage and repair in terms of strand breaks in PBMCs by means of the automated Fluorimetric Detection of Alkaline Unwinding (FADU) assay. DNA repair capacity was assessed by repeatedly measuring the amount of intact DNA up to 90 min after standardized X-irradiation of the cells. RESULTS: General linear models revealed that elevated levels of basal DNA damage (ß=-0.34, p=0.013, f=0.33) as well as impaired capacity to repair damaged DNA (F(1/50)=5.40, p=0.024, f=0.33) with increasing BMI, but not with vital exhaustion (p's ≥ 0.63). CONCLUSION: Our findings point to DNA integrity impairments with increasing BMI, already in the overweight range, and suggest impaired DNA repair as a potential underlying molecular mechanism. In contrast, the psychological factor vital exhaustion was not associated with DNA damage or DNA repair capacity.

Do Hypertensive Men Spy With an Angry Little Eye? Anger Recognition in Men With Essential Hypertension - Cross-sectional and Prospective Findings.

BACKGROUND: Higher trait anger has inconsistently been associated with hypertension and hypertension development, but social context in terms of recognition of other persons' anger has been neglected in this context. PURPOSE: Here, we investigated anger recognition of facial affect and trait anger in essential hypertensive and normotensive men in addition to prospective associations with blood pressure (BP) increases. METHODS: Baseline assessment comprised a total of 145 participants including 57 essential hypertensive and 65 normotensive men who were otherwise healthy and medication-free. Seventy-two eligible participants additionally completed follow-up assessment 3.1 (±0.08 SEM) years later to analyze BP changes over time. We assessed emotion recognition of facial affect with a paradigm displaying mixed facial affect of two morphed basic emotions including anger, fear, sadness, and happiness. Trait anger was assessed with the Spielberger trait anger scale. RESULTS: Cross-sectionally, we found that with increasing BP, hypertensive men overrated anger displayed in facial expressions of mixed emotions as compared to normotensive men (ps ≤ .019) while there were no differences in trait anger (p = .16). Prospectively, the interaction between mean anger recognition and trait anger independently predicted BP increases from baseline to follow-up (ps ≤ .043), in that overrating displayed anger predicted future BP increases only if trait anger was high. CONCLUSIONS: Our findings indicate an anger recognition bias in men with essential hypertension and that overrating displayed anger in combination with higher trait anger seems to predict future BP increases. This might be of clinical relevance for the development and progression of hypertension and cardiovascular disease.

Aldosterone secretion during the day: Salivary aldosterone awakening response and daytime levels.

BACKGROUND: The mineralocorticoid hormone aldosterone is a key regulator of the sodium-potassium balance and blood pressure. In excess, aldosterone relates to hypertension and cardiovascular disease (CVD). Here, we systematically investigated aldosterone secretion during the day in terms of salivary aldosterone awakening response (AldAR) and salivary aldosterone daytime levels (AldDay) under controlled conditions in participants' natural environment including assessment of potential confounding variables. METHODS: In 40 healthy young men, saliva samples for AldAR were collected immediately after awakening and 15, 30, 45, and 60 min thereafter. AldDay levels were measured in 1 h intervals from 9:00-22:00 h. Analyses were complemented by salivary cortisol assessment. Fluid and food intake was standardized and as potential confounders, we assessed awakening time and sleep duration, age, BMI and MAP, as well as chronic stress. RESULTS: Awakening was followed by significant increases in salivary aldosterone (p = .004, f= 0.31), returning to baseline levels > 60 min later. Longer sleep duration was associated with lower AldAR (p < .001, f= 0.36). Over the course of the day we observed a continuous decrease of AldDay (p < .001, f= 0.45). Longer sleep duration (p = .097, f= .21), later time of awakening (p < .001, f= .29), and higher chronic stress (p = .041, f= .23) were associated with AldDay characteristics. Circadian aldosterone secretion was positively associated with most cortisol measures. CONCLUSIONS: We observed an awakening response in salivary aldosterone and could confirm a decrease in aldosterone levels during the day, comparable to cortisol. Significant confounders were sleep-related variables and chronic stress. Clinical implications of circadian aldosterone secretion with respect to CVD risk remain to be elucidated.

Determinants and Mechanisms of the Renin-Aldosterone Stress Response.

OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) plays a relevant role in regulating blood pressure and thus maintaining cardiovascular homeostasis. Although it was recently shown that RAAS parameters are responsive to acute psychosocial stress, the psychobiological determinants of the acute stress-induced RAAS activation have not yet been investigated. In a randomized placebo-controlled design, we investigated potential psychological and physiological determinants of the RAAS response and underlying mechanisms. METHODS: Fifty-seven young healthy male participants underwent either an acute standardized psychosocial stress test or a nonstress placebo task. We measured aldosterone in plasma and saliva, as well as renin, and the stress-reactive endocrine measures adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine in plasma at rest, immediately after the task and several times up to 3 hours thereafter. Moreover, we assessed stress-reactive psychological (anticipatory cognitive stress appraisal, mood, physical discomfort) and basal demographic-physiological measures (age, body mass index, blood pressure). RESULTS: Acute psychosocial stress elicited changes in all assessed endocrine (p values ≤ .028, ηp2 values ≥ 0.07) and stress-reactive psychological measures (p values ≤ .003, ηp2 values ≥ 0.15). The basal parameter body mass index, the stress-reactive endocrine parameters ACTH and norepinephrine, and the psychological parameter anticipatory stress appraisal were identified as determinants of higher RAAS parameter reactivity to acute psychosocial stress. The association between anticipatory cognitive stress appraisal and plasma RAAS measures was fully mediated by ACTH increases (p values ≤ .044, ηp2 values ≥ 0.05). CONCLUSIONS: Cognitive stress appraisal processes seem to modulate RAAS stress reactivity. This points to potential clinical implications for psychoeducative therapeutical interventions targeting stress appraisal processes to reduce endocrine stress reactivity.

Acute Stress-Induced Blood Lipid Reactivity in Hypertensive and Normotensive Men and Prospective Associations with Future Cardiovascular Risk.

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension.

Aldosterone hyperreactivity to acute psychosocial stress induction in men with essential hypertension.

Essential hypertension is a pivotal risk factor for the development of cardiovascular disease (CVD). Hypertensives exhibit greater stress-induced responses in various physiological systems considered to contribute to CVD progression. Whether this stress hyperreactivity extends to the adrenal hormone aldosterone has not yet been investigated in essential hypertension. Here, we investigated reactivity of plasma aldosterone to acute psychosocial stress induction in hypertensive and normotensive men. 21 hypertensive men and 25 normotensive controls underwent the standardized Trier-Social-Stress-Test (TSST). We repeatedly assessed plasma aldosterone before and up to 1 h after TSST cessation. Acute psychosocial stress induced significantly greater increases in hypertensives as compared to normotensives (F(3.60, 158.50) = 3.75; p = .008, f = 0.29). Our findings suggest stress-induced hyperreactivity of aldosterone in essential hypertension. Potential implications for stress-related cardiovascular risk remain to be elucidated.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension.

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p's > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Acute Stress Improves Concentration Performance.

Acute stress can have both detrimental and beneficial effects on cognitive processing, but effects on concentration performance remain unclear. Here, we investigate the effects of acute psychosocial stress on concentration performance and possible underlying physiological and psychological mechanisms. The study sample comprised 47 healthy male participants who were randomly assigned either to a psychosocial stress situation (Trier Social Stress Test) or a neutral control task. Concentration performance was assessed using the d2 Test of Attention before and 30 min after the stress or control task. Salivary cortisol and alpha-amylase were repeatedly measured before and up to 1 hr after stress. We repeatedly assessed state anxiety using the State-Trait Anxiety Inventory and anticipatory cognitive stress appraisal using the Primary Appraisal Secondary Appraisal questionnaire. The stress group showed a significantly stronger improvement of concentration performance compared to the control group (p = .042). Concentration performance improvement was predicted by increased state anxiety (p = .020) and lower cortisol (stress) changes (p = .043). Neither changes in alpha-amylase nor cognitive stress appraisal did relate to concentration performance. Our results show improved concentration performance after acute psychosocial stress induction that was predicted by higher state anxiety increases and lower cortisol increases. This points to a potential modulating role of specific psycho-emotional and physiological factors with opposite effects.

Kinetics and Interrelations of the Renin Aldosterone Response to Acute Psychosocial Stress: A Neglected Stress System.

CONTEXT: The renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular homeostasis and its dysfunction relates to negative health consequences. Acute psychosocial stress seems to activate the RAAS in humans, but stress kinetics and interrelations of RAAS parameters compared with a nonstress control group remain inconclusive. OBJECTIVE: We systematically investigated in a randomized placebo-controlled design stress kinetics and interrelations of the reactivity of RAAS parameters measured in plasma and saliva to standardized acute psychosocial stress induction. METHODS: 58 healthy young men were assigned to either a stress or a placebo control group. The stress group underwent the Trier Social Stress Test (TSST), while the control group underwent the placebo TSST. We repeatedly assessed plasma renin, and plasma and salivary aldosterone before and up to 3 hours after stress/placebo. We simultaneously assessed salivary cortisol to validate successful stress induction and to test for interrelations. RESULTS: Acute psychosocial stress induced significant increases in all endocrine measures compared with placebo-stress (all P ≤ .041). Highest renin levels were observed 1 minute after stress, and highest aldosterone and cortisol levels 10 and 20 minutes after stress, with salivary aldosterone starting earlier at 1 minute after stress. Renin completed recovery at 10 minutes, cortisol at 60 minutes, salivary aldosterone at 90 minutes, and plasma aldosterone at 180 minutes after stress. Stress increase scores of all endocrine measures related to each other, as did renin and cortisol areas under the curve with respect to increase (AUCi) and salivary and plasma aldosterone AUCi (all P ≤ .047). CONCLUSIONS: Our findings suggest that in humans acute psychosocial stress induces a differential and interrelated RAAS parameter activation pattern. Potential implications for stress-related cardiovascular risk remain to be elucidated.