Glucocorticoids can down-regulate immune activity, but acute stress has been reported to increase both cortisol and levels of plasma cytokines. We investigated individual differences in cortisol responses and their associations with proinflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), cardiovascular activity, and mental health. Saliva samples and blood were taken from 199 healthy middle-aged participants of the Whitehall II cohort at baseline, immediately after stress and 45min later. We defined the 40% of participants with the highest cortisol response to stress as the cortisol responder group and 40% with the lowest response as the cortisol non-responder group. Plasma IL-6 was higher and the IL-1ra response to stress was greater in the cortisol non-responder group. The cortisol non-responders showed lower heart rate variability than the cortisol responders. The cortisol responder group experienced more subjective stress during the tasks and reported more impaired mental health than the non-responders. We conclude that individual variations in neuroendocrine stress responsivity may have an impact on proinflammatory cytokines, and that both high and low cortisol stress responsiveness has potentially adverse effects.

Associations between natural killer (NK) cell, proinflammatory cytokine stress responsivity, and cardiac autonomic responses (indexed by heart rate and heart rate variability) were assessed in 211 middle-aged men and women. Blood was drawn at baseline, immediately following color–word interference and mirror tracing tasks for the assessment of NK cell numbers, and 45 min post-stress for assessing plasma interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) responses. Heart rate variability was measured as the root mean square of successive differences (RMSSD) in R–R intervals. Increases in NK cell counts following stress were positively associated with heart rate responses independently of age, sex, socioeconomic status, smoking, and change in hematocrit. Heart rate 45 min post-stress was positively associated with plasma IL-6 post-stress, and with TNFα changes from baseline, independently of covariates. No relationship between immune responses and heart rate variability was observed. We conclude that individual differences in sympathetically-driven cardiac stress responses are associated with NK and proinflammatory cytokine responses to psychological stress.

Social disparities in health persist into old age, and differences in psychophysiological responsivity may contribute to this pattern. We assessed whether higher socioeconomic status (SES) is associated with attenuated cardiovascular and neuroendocrine responses elicited by cognitive tasks in old age. We tested 132 community-dwelling men and women aged 65–80 years, divided on the basis of educational attainment into higher and lower SES groups, and compared them with 26 higher educated participants aged 27–42 years. Blood pressure, hemodynamic variables and salivary cortisol were assessed in response to the performance of three cognitive tasks, and then during recovery. Older groups showed smaller heart rate and larger cortisol changes than younger participants. Post-task recovery in heart rate, stroke volume, pre-ejection period, and systolic blood pressure was greatest in the younger group, least in the older/lower education group, and intermediate in the older/higher education group. SES did not influence the increased cortisol responsivity of older participants. The results are consistent with the notion that higher SES protects against age-related changes in cardiovascular response profiles, particularly during recovery.

Objective 
To assess whether variation in the rate of cardiovascular recovery following exposure to acute psychological stress predicts changes in blood pressure longitudinally, independently of blood pressure at baseline and other covariates.
Design 
A 3-year longitudinal study.
Participants 
A total of 209 men and women aged 45–59 years at baseline, with no history of cardiovascular disease including hypertension.
Method 
Measurement of blood pressure, heart rate, heart rate variability, cardiac index and total peripheral resistance at rest, during two moderately stressful behavioural tasks and up to 45 min post-stress. Stress reactivity was defined as the difference in values between tasks and baseline, and post-stress recovery as the difference between recovery levels and baseline.
Outcome measures 
Resting blood pressure measured at baseline and 3 years later. Seven individuals had been prescribed hypertensive medication on follow-up.
Results 
Increases in systolic blood pressure (SBP) were predicted by impaired post-stress recovery of SBP (P < 0.001), diastolic blood pressure (DBP) (P < 0.001) and total peripheral resistance (P = 0.003), independently of baseline blood pressure, age, gender, socio-economic status, hypertensive medication, body mass and smoking. The adjusted odds of an increase in SBP ≥ 5 mmHg were 3.50 [95% confidence interval (CI) 1.19 to 10.8] for individuals with poor compared with effective post-stress recovery of SBP. Three-year increases in diastolic pressure were predicted by impaired recovery of SBP (P < 0.001) and DBP (P = 0.009) pressure and by heart rate variability during tasks (P = 0.002), independently of covariates. Conclusions  Impaired post-stress recovery and less consistently heightened acute stress reactivity may index disturbances in the regulation of cardiovascular stress responses that contribute to longitudinal changes in blood pressure in middle-aged men and women.

Objectives: 
To examine the association between physical fitness, cardiac parasympathetic control, and inflammatory cytokine responses to mental stress. Exercise and physical fitness may act as a buffer to the detrimental effects of psychosocial stress exposure.
Methods: 
Participants were 207 men and women (52 ± 3 years) drawn from the Whitehall II epidemiological cohort. Participants completed two mental stressors consisting of a 5-minute Stroop task and a 5-minute mirror tracing task. Blood samples were obtained during baseline and 45 minutes post stress. Heart rate variability (HRV) was measured during baseline, stress, and recovery. Physical fitness was assessed from a submaximal exercise test.
Results: 
Interleukin (IL)-6 and IL-1 receptor antagonist were increased significantly at 45 minutes post stress. Multiple linear regression analysis, adjusted for age, body mass index, gender, smoking, alcohol, grade of employment, and basal levels of inflammatory markers demonstrated that exercise heart rate (a fitness indicator) was related to IL-6 (β = 0.24; p = .005) and tumor necrosis factor (TNF)-α responses to stress (β = 0.27; p = .002). Exercise heart rate was also related to the HRV response to stress (β = −0.23; p = .02). A higher systolic blood pressure response to exercise was a predictor of TNF-α responses to stress (β = 0.18; p = .03).
Conclusions: 
Physical fitness (as indexed by lower exercise heart rate) is associated with smaller inflammatory cytokine responses to acute mental stress, an effect that may be partly mediated through parasympathetic pathways. This may be one of the mechanisms by which physical fitness confers protection against cardiovascular risk.
IL = interleukin;
TNF = tumor necrosis factor;
HRV = heart rate variability;
CHD = coronary heart disease;
BMI = body mass index.

Heightened cardiovascular stress responsivity is associated with cardiovascular disease, but the origins of heightened responsivity are unclear. The present study investigated whether disturbances in cardiovascular responsivity were evident in individuals with a family history of cardiovascular disease risk. Data were collected from 60 women and 31 men with an average age of 21.4 years. Family history of cardiovascular disease risk was defined by the presence of coronary heart disease, hypertension, diabetes or high cholesterol in participants’ parents and grandparents; 75 participants had positive, and 16 had negative family histories. Systolic and diastolic blood pressure (BP), heart rate and heart rate variability were measured continuously for 5 min periods at baseline, during two mental stress tasks (Stroop and speech task) and at 10–15 min, 25–30 min and 40–45 min post-stress. Individuals with a positive family history exhibited significantly greater diastolic BP reactivity and poorer systolic and diastolic BP recovery from the stressors in comparison with family history negative individuals. In addition, female participants with a positive family history had heightened heart rate and heart rate variability reactivity to stressors. These effects were independent of baseline cardiovascular activity, body mass index, waist to hip ratio and smoking status. Family history of hypertension alone was not associated with stress responsivity. The findings indicate that a family history of cardiovascular disease risk influences stress responsivity which may in turn contribute to risk of future cardiovascular disorders.

Acute mental stress tests have helped to clarify the pathways through which psychosocial factors are linked to disease risk. This methodology is now being used to investigate potentially protective psychosocial factors. We investigated whether global self-esteem might buffer cardiovascular and inflammatory responses to acute stress. One hundred and one students completed the Rosenberg Self-Esteem Scale. Heart rate and heart rate variability (HRV) were recorded for 5min periods at baseline, during two mental stress tasks, (a speech and a color-word task) and 10, 25 and 40min into a recovery period. Plasma levels of tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra) were assessed at baseline, immediately post-stress and after 45min recovery. Repeated measures analysis of variance demonstrated that heart rate levels were lower across all time points in those with high self-esteem, although heart rate reactivity to stress was not related to self-esteem. There were no differences in baseline HRV, TNF-α, IL-6 or IL-1Ra. Multiple linear regressions revealed that greater self-esteem was associated with a smaller reduction in heart rate variability during the speech task, but not the color-word task. Greater self-esteem was associated with smaller TNF-α and IL-1Ra responses immediately following acute stress and smaller IL-1Ra responses at 45min post-stress. In conclusion, global self-esteem is associated with lower heart rate and attenuated HRV and inflammatory responses to acute stress. These responses could be processes through which self-esteem protects against the development of disease.

Obesity is associated with an elevated risk of hypertension and cardiovascular disease. The adipocyte hormone leptin, which stimulates energy expenditure in animals by activating the sympathetic nervous system (SNS), is believed to play a role in this association. However, evidence in humans remains sparse. We investigated the relationship between circulating leptin and cardiovascular and inflammatory responses to acute psychological stress in humans. Participants were 32 men and 62 women aged 18–25 years. Cardiovascular activity was assessed using impedance cardiography at baseline, during acute laboratory stress, and during a 45-min recovery period. Plasma cytokines were measured in blood drawn at baseline and 45-min poststress. In women only, baseline plasma leptin was significantly associated with stress-induced changes in heart rate (β = 0.53, P = 0.006), heart rate variability (HRV) (β = −0.44, P = 0.015), and cardiac preejection period (PEP) (β = −0.51, P = 0.004), independent of age, adiposity, and smoking. Women’s plasma leptin levels also correlated with stress-induced elevations in the proinflammatory cytokine interleukin-6 (IL-6) (β = 0.35, P = 0.042). Circulating leptin is an independent predictor of sympathetic cardiovascular activity, parasympathetic withdrawal, and inflammatory responses to stress in women. Because cardiovascular and inflammatory stress responses are predictive of future cardiovascular disease, leptin may be a mechanism mediating the adverse effects of stress and obesity on women’s cardiovascular health.

Exaggerated blood pressure (BP) response to exercise is a strong predictor of cardiovascular disease, although the mechanisms remain unknown. The purpose was to examine the association between systemic markers of vascular inflammation and exercise blood pressure (BP) responses. Participants were 191 healthy men and women (aged 45–59 years). Blood pressure was measured at baseline and during 8 min of steady state cycling ergometry exercise (at 50 W). Markers of vascular inflammation (fibrinogen, von Willebrand factor antigen, tumour necrosis factor-α, interleukin-6 [IL-6], C-reactive protein [CRP]) were measured at baseline together with other traditional risk factors including central adiposity, smoking, alcohol, and habitual physical activity. CRP (β = 0.30, p < 0.001), IL-6 (β = 0.25, p = 0.001), and fibrinogen (β = 0.14, p = 0.04) were associated with exercise systolic BP. The association with CRP remained significant after adjustment for age, sex, resting BP, and other risk factors. Other independent predictors of exercise BP included resting BP, female gender, waist–hip ratio, lower employment grade, and low physical activity level. In summary, central adiposity and vascular inflammatory processes may underlie exaggerated BP responses to acute exercise.