Procoagulant stress reactivity and recovery in apparently healthy men with systolic and diastolic hypertension.

OBJECTIVE: The aim of this study was to investigate whether systemic systolic hypertension (SHT) and diastolic hypertension (DHT) are associated with an exaggerated response of factor VII clotting activity (FVII:C), factor VIII clotting activity (FVIII:C), fibrinogen, and d-dimer to acute psychosocial stress. METHODS: We performed the 15-min Trier Social Stress Test (i.e., combination of task preparation, job interview and mental arithmetic) in a sample of 42 middle-aged apparently healthy and unmedicated men with normal and elevated blood pressure (BP) (i.e. screening systolic and/or diastolic BP>or=130/85 mmHg). Blood samples for coagulation measures were obtained immediately pre and post stress and 20 min and 60 min thereafter. Repeated measures analyses of covariance controlled for age, body mass index, screening mean arterial BP, and resting level of coagulation factors. RESULTS: There was a stress-by-DHT interaction for changes across all time points in FVII:C (P=.027), FVIII:C (P=.018), and d-dimer (P=.011) explaining between 14% and 17% of the variance. Compared to subjects without DHT, diastolic hypertensives had higher FVII:C immediately post stress (P=.085, Cohen's d=.60) and at 20-min recovery (P=.19, d=.46), higher FVIII:C at 20- (P=.028, d=.78) and at 60-min (P=.035, d=.75) recovery, and higher D-dimer at 20-min recovery (P=.10, d=.58). A significant stress-by-SHT interaction for fibrinogen (P=.050) became nonsignificant when controlling for covariates. CONCLUSION: Diastolic hypertension exaggerated the acute procoagulant response to stress in middle-aged men. This effect was particularly observed during recovery of hypercoagulability from stress. The findings suggest a psychobiological mechanism linking stress with an increased atherothrombotic risk in hypertensive individuals.

Perfectionism and the cortisol response to psychosocial stress in men.

OBJECTIVE: To test the hypothesis that perfectionism is an important moderator of the neuroendocrine stress response, with higher perfectionism predicting increased neuroendocrine activation. METHODS: A total of 50 middle-aged men underwent an acute standardized psychosocial stress task (Trier Social Stress Test). Perfectionism, cognitive appraisal of the stressful situation, trait anxiety, and various personality characteristics were assessed with questionnaires. Salivary cortisol, plasma epinephrine and norepinephrine, blood pressure, and heart rate were analyzed before and after stress. Circadian profiles of cortisol secretion during the day and in response to awakening were analyzed to assess basal activity of the hypothalamus-pituitary-adrenal (HPA) axis. Multiple regression analyses were conducted to identify predictors of the neuroendocrine stress response. RESULTS: Perfectionism was significantly associated with area under the total response curve with respect to increase (AUCi) of cortisol (r = 0.322, p = .046), but not with AUCi of norepinephrine (r = -0.217, p = .152) or AUCi of epinephrine (r = 0.116, p = .477). Hence, AUCi of cortisol was the main criterion. As possible predictors, trait anxiety, neuroticism, vital exhaustion, secondary appraisal, depression, and openness were considered. Regression analyses demonstrated that only perfectionism (beta = 0.45, p = .002) and secondary appraisal (beta = 0.50, p = .001) were independent predictors of AUCi of cortisol, the final model explaining 45% of the total variance in cortisol response (R2 = 0.45, "shrunken" R2 [sR2] = 0.38); perfectionism alone accounted for 18% of this variance (deltaR2 = 0.18, sR2 = 0.19). CONCLUSION: The typical cognitions, and presumably the associated emotions, of perfectionists seem to contribute independently to stress-induced bodily responses, including HPA axis activation, in response to psychosocial stress.

Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic hypertension: blunted cortisol response to awakening and lower negative feedback sensitivity.

BACKGROUND: Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile. METHODS: The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night. RESULTS: Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives. CONCLUSION: We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.

Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men.

OBJECTIVE: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. METHODS: Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. RESULTS: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. CONCLUSIONS: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

BACKGROUND: Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. METHODS: We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. RESULTS: At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. CONCLUSIONS: MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Low social support and poor emotional regulation are associated with increased stress hormone reactivity to mental stress in systemic hypertension.

CONTEXT: There is strong evidence for a physiological hyperreactivity to stress in systemic hypertension, but data on associated or potentially moderating psychological factors are scarce. OBJECTIVE: The objective of the study was to identify psychological correlates of physiological stress reactivity in systemic hypertension. DESIGN: This was a cross-sectional, quasi-experimentally controlled study. Study participants underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. SETTING: The study was conducted in the population in the state of Zurich, Switzerland. SUBJECTS: Subjects included 22 hypertensive and 26 normotensive men (mean +/- sem 44 +/- 2 yr). MAIN OUTCOME MEASURES: We assessed the psychological measures social support, emotional regulation, and cognitive appraisal of the stressful situation. Moreover, we measured salivary cortisol and plasma epinephrine and norepinephrine before and after stress and several times up to 60 min thereafter as well as blood pressure and heart rate. RESULTS: We found poorer hedonistic emotional regulation (HER) and lower perceived social support in hypertensives, compared with normotensives (P < 0.01). Compared with normotensives, hypertensives showed higher cortisol, epinephrine, and norepinephrine secretions after stress (P < 0.038) as well as higher systolic and diastolic blood pressure (P < 0.001). Cortisol reactivity and norepinephrine secretion were highest in hypertensive men with low HER (P < 0.05). In contrast, hypertensives with high HER did not significantly differ from normotensives in both cortisol and norepinephrine secretion after stress. Epinephrine secretion was highest in hypertensives with low social support but was not different between hypertensives with high social support and normotensives. CONCLUSIONS: The findings suggest that both low social support and low HER are associated with elevated stress hormone reactivity in systemic hypertension.