Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women.

Low socioeconomic status (SES) may be associated with accelerated biological aging, but findings relating SES with telomere length have been inconsistent. We tested the hypotheses that shorter telomere length and telomerase activity would be related more robustly to education, an early life indicator of socioeconomic position, than to current indicators of socioeconomic circumstances. Healthy men and women aged 53-76 years from the Whitehall II epidemiological cohort provided blood samples from which telomere length was assessed in 448 and telomerase activity in 416. Educational attainment was classified into four levels, while household income and grade of employment were measured as indicators of current socioeconomic circumstances. Age, gender, blood pressure, glycated hemoglobin, high density lipoprotein cholesterol, smoking, body mass index and physical activity were included as covariates. We found that lower educational attainment was associated with shorter telomere length after controlling statistically for biological and behavioral covariates. Neither household income nor employment grade was related to telomere length. The association between telomere length and education remained significant after adjusting for current socioeconomic circumstances. In men, highest levels of telomerase activity were found in the lowest education group. We conclude that low SES defined in terms of education but not current socioeconomic circumstances is associated with shortened telomeres. Low educational attainment may be an indicator of long-term SES trajectories, and be associated with accumulated allostatic load resulting in telomere shortening. Education may also promote problem-solving skills leading to reduced biological stress responsivity, with favorable consequences for biological aging.

Emotional triggering of cardiac events.

Psychological factors may contribute not only to the evolution of coronary atherosclerosis and long-term risk of coronary heart disease, but also to the triggering of acute cardiac events in patients with advanced atherosclerosis. Evidence for emotional triggering of cardiac events derives both from population-based studies of hospital admissions and sudden deaths following major traumas such as earthquakes and terrorist incidents, and from individually based interview studies with survivors of acute coronary syndromes (ACS). The latter indicate that acute anger, stress and depression or sadness may trigger ACS within a few hours in vulnerable individuals. The psychobiological processes underlying emotional triggering may include stress-induced haemodynamic responses, autonomic dysfunction and parasympathetic withdrawal, neuroendocrine activation, inflammatory responses involving cytokines and chemokines, and prothrombotic responses, notably platelet activation. These factors in turn promote coronary plaque disruption, myocardial ischaemia, cardiac dysrhythmia and thrombus formation. The implications of these findings for patient care and ACS prevention are outlined.

Dispositional optimism and stress-induced changes in immunity and negative mood.

Evidence suggests that optimism may be protective for health during times of heightened stress, yet the mechanisms involved remain unclear. In a double-blind placebo-controlled study, we recently showed that acute psychological stress and an immune stimulus (Typhim-Vi typhoid vaccine) synergistically increased serum levels of interleukin-6 (IL-6) and negative mood in 59 healthy men. Here we carried out further analysis of this sample to investigate the relationship between dispositional optimism and stress-induced changes in immunity and mood. Volunteers were randomly assigned to one of four experimental conditions in which they received either typhoid vaccine or saline placebo, and then rested or completed two mental tasks. In the stress condition, optimism was inversely related to IL-6 responses, independent of age, BMI, trait CES-D depression and baseline IL-6. This relationship was present across both stress groups (combining vaccine and placebo) and was not present in the vaccine/stress group alone, suggesting that optimism protects against the inflammatory effects of stress rather than vaccine per se. Typhoid vaccine induced a significant increase in participants' circulating anti-Vi antibody levels. Stress had no effect on antibody responses overall. However, in the vaccine/stress group, there was a strong positive association between optimism and antibody responses, indicating that stress accentuated the antibody response to vaccine in optimists. Across the complete sample, more optimistic individuals had smaller increases in negative mood and less reduction in mental vigour. Together these findings suggest that optimism may promote health, by counteracting stress-induced increases in inflammation and boosting the adjuvant effects of acute stress.

Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans.

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Self-esteem levels and cardiovascular and inflammatory responses to acute stress.

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 5 min periods at baseline, during two mental stress tasks, (a speech and a color-word task) and 10, 25 and 40 min into a recovery period. Plasma levels of tumor-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra) were assessed at baseline, immediately post-stress and after 45 min 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-alpha, 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-alpha and IL-1Ra responses immediately following acute stress and smaller IL-1Ra responses at 45 min 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.

Arterial stiffness and inflammatory response to psychophysiological stress.

The processes through which psychological stress influences cardiovascular disease are poorly understood, but may involve activation of hemodynamic, neuroendocrine and inflammatory responses. We assessed the relationship between carotid arterial stiffness and inflammatory responses to acute psychophysiologic stress. Participants were 155 healthy men and women aged 55.3, SD 2.7 years. Blood samples for the assessment of plasma fibrinogen, tumor necrosis factor (TNF) alpha and interleukin (IL) 6 were drawn at baseline, immediately following standardized behavioral tasks, and 45 min later. Carotid artery stiffness was measured ultrasonically three years later, and blood pressure and heart rate responses were recorded. The tasks induced substantial increases in blood pressure and heart rate, together with increased fibrinogen, TNFalpha and IL-6 concentration. Carotid stiffness was positively associated with body mass, waist/hip ratio, blood pressure, low density lipoprotein cholesterol, and C-reactive protein, and inversely with high density lipoprotein and grade of employment. Baseline levels of inflammatory variables were not related to carotid artery stiffness. But carotid stiffness was greater in participants with larger fibrinogen (p=0.037) and TNFalpha (p=0.036) responses to psychophysiological stress. These effects were independent of age, gender, grade of employment, smoking, body mass, waist/hip ratio, systolic and diastolic pressure, high and low density lipoprotein cholesterol, and C-reactive protein. There were no associations between carotid stiffness and stress responses in IL-6, blood pressure, or heart rate. We conclude that individual differences in inflammatory responses to psychophysiological stress are independently related to structural changes in artery walls that reflect increased cardiovascular disease risk.

MT1 melatonin receptor internalization underlies melatonin-induced morphologic changes in Chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1/2 and microtubule modulation.

Melatonin induces cellular differentiation in numerous cell types. Data show that multiple mechanisms are involved in these processes that are cell-type specific and may be receptor dependent or independent. The focus of this study was to specifically assess the role of human MT1 melatonin receptors in cellular differentiation using an MT1-Chinese hamster ovary (CHO) model; one that reproducibly produces measurable morphologic changes in response to melatonin. Using multiple approaches, we show that melatonin induces MT1-CHO cells to hyperelongate through a MEK 1/2, and ERK 1/2-dependent mechanism that is dependent upon MT1 receptor internalization, Gi protein activation, and clathrin-mediated endocytosis. Using immunoprecipitation analysis, we show that MT1 receptors form complexes with Gi(alpha) 2,3, Gq(alpha), beta-arrestin-2, MEK 1/2, and ERK 1/2 in the presence of melatonin. We also show that MEK and ERK activity that is induced by melatonin is dependent on Gi protein activation, clathrin-mediated endocytosis and is modulated by microtubules. We conclude from these studies that melatonin-induced internalization of human MT1 melatonin receptors in CHO cells is responsible for activating both MEK 1/2 and ERK 1/2 to drive these morphologic changes. These events, as mediated by melatonin, require Gi protein activation and endocytosis mediated through clathrin, to form MT1 receptor complexes with beta-arrestin-2/MEK 1/2 and ERK 1/2. The MT1-CHO model is invaluable to mapping out signaling cascades as mediated through MT1 receptors especially because it separates out MEK/ERK 1/2 activation by MT1 receptors from that of receptor tyrosine kinases.

Family history of cardiovascular disease is associated with cardiovascular responses to stress in healthy young men and women.

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.

Parental adiposity and cortisol awakening responses in young men and women.

A heightened cortisol awakening response (CAR) is associated with adiposity in middle-aged men, but the causal significance of this effect is not known. We hypothesised that if disturbance in cortisol secretion is involved in the development of overweight and obesity, then it might be present in normal weight adults at increased risk of obesity on account of parental adiposity. The CAR and cortisol profile over the day were measured in 33 men and 62 women aged 18-25 years. Parental adiposity was assessed with figure ratings derived from the Contour Drawing Rating Scale, and these were correlated with parental self-reported body mass index (BMI) in a subset of participants (r=0.66-0.79). In men, a positive association was observed between the CAR and their judgements of their fathers' adiposity after controlling for age, smoking status, time of waking, and the participants' own BMI; the correlation was 0.56 (P=0.008) for the cortisol increase between waking and 30 min, and 0.47 (P=0.028) for the cortisol area under the curve. The correlation between the CAR and fathers' own reported BMI and figures ratings were also significant. The relationship between parental adiposity and the CAR in women was inconsistent, and the associations between the CAR and opposite gender parental adiposity were not significant. Parental adiposity was not related to cortisol output over the rest of the day or to the slope between waking and evening in either sex. The results of this study suggest that disturbances of cortisol secretion may present before the emergence of heightened adiposity in young men at raised risk for obesity.

Stress-induced increases in interleukin-6 and fibrinogen predict ambulatory blood pressure at 3-year follow-up.

BACKGROUND: The biological mechanisms underlying the association between psychological stress and hypertension are poorly understood. Increased plasma concentrations of the inflammatory proteins interleukin-6 and fibrinogen are commonly reported both in hypertensive patients and in people subject to chronic psychological stress. Recent laboratory studies have also shown that acute psychological stress increases plasma interleukin-6 and fibrinogen concentrations in healthy individuals. OBJECTIVE: To investigate the relationship between stress-induced inflammatory responses and blood pressure using a longitudinal design. METHODS: Participants were 153 individuals from the Whitehall II cohort. Blood pressure, plasma interleukin-6 and fibrinogen were assessed in response to an acute laboratory stressor, and ambulatory blood pressure was monitored on a separate day. Three years later, a follow-up day of ambulatory blood pressure monitoring was carried out. RESULTS: Individual differences in systolic pressure, fibrinogen and interleukin-6 stress responses predicted ambulatory blood pressure at the 3-year follow-up. Larger increases in ambulatory systolic pressure over the 3-year period were predicted by larger acute fibrinogen and interleukin-6 stress responses, independently of previous ambulatory blood pressure, acute blood pressure stress responses, age, sex, body mass and smoking. CONCLUSION: Given the important roles of interleukin-6 and fibrinogen in hypertensive pathophysiology, these results indicate that psychological stress could promote hypertension through stimulating these inflammatory proteins.

Changes in financial strain over three years, ambulatory blood pressure, and cortisol responses to awakening.

OBJECTIVE: Chronic psychosocial stress has been associated cross-sectionally with ambulatory blood pressure and with salivary cortisol, but there have been few longitudinal studies of the effects of changes in chronic stress. We assessed the influence of changes in financial strain on ambulatory blood pressure and salivary cortisol. METHODS: Data were analyzed from 160 men and women age 47 to 59 years at the first assessment (T1) who repeated ambulatory monitoring 3 years later (T2). We analyzed change in financial strain as a continuous variable, and specifically compared people who did and did not report an improvement in financial strain. RESULTS: Change in financial strain was associated with change in ambulatory systolic pressure after controlling for T1 ambulatory systolic pressure, gender, socioeconomic position, age, smoking, body mass index, and T1 financial strain (p = .041). Systolic pressure at T2 was lower in the improved financial strain (121.7 +/- 11.2 mm Hg) than in the worse/no change group (125.5 +/- 11.5 mm Hg; p = .029). The corresponding diastolic pressures averaged 78.5 +/- 7.1 mm Hg and 80.7 +/- 7.9 mm Hg, respectively (p = .061). The cortisol awakening response (difference between waking and 30 minutes later) was lower (p = .048) in men who reported improved financial strain, controlling for T1 cortisol response, socioeconomic position, age, smoking, time of waking, and T1 financial strain. There were no differences in the slope of cortisol decline over the day or in evening values. CONCLUSION: These longitudinal data extend cross-sectional findings in showing associations between favorable changes in chronic stress and reduced cardiovascular and neuroendocrine activation in everyday life.

Associations between acute lipid stress responses and fasting lipid levels 3 years later.

The authors assessed the association between lipid responses to acute mental stress and fasting serum lipid levels 3 years later in 199 middle-aged men and women. Total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol increased following moderately stressful behavioral tasks. LDL cholesterol, HDL cholesterol, and total:HDL ratio measured 3 years later were predicted by acute stress responses independent of gender, age, socioeconomic position, change in body mass, smoking, alcohol consumption, or hormone replacement therapy baseline lipid levels. The odds of clinically elevated cholesterol were significantly greater in the highest compared with the lowest stress tertile, independent of baseline levels and covariates. Acute lipid stress responsivity may reflect processes that contribute to the development of elevated blood cholesterol concentration.

The influence of psychological stress and socioeconomic status on platelet activation in men.

OBJECTIVE: Circulating monocyte- and neutrophil-platelet aggregates are sensitive markers of in vivo platelet activation. Socioeconomic status is inversely associated with risk of coronary heart disease. We assessed the impact of psychological stress on leukocyte-platelet aggregates in men from higher and lower socioeconomic status groups. METHODS: Participants were 37 healthy non-smoking men aged 30-59 years, divided by occupation into higher and lower social status groups. Blood was drawn at baseline, immediately following stressful behavioural tasks, and at 30 and 75 min post-stress, and aggregates were analysed using flow cytometry. Cardiovascular and subjective stress responses were also monitored. RESULTS: There were significant increases following stress in monocyte-, neutrophil-, lymphocyte- and total leukocyte-platelet aggregates (all P<0.05). The largest responses were in monocyte-platelet (21% increase) and neutrophil-platelet (16.7% increase) aggregates. Lower socioeconomic status men had greater numbers of leukocyte-platelet aggregates throughout, but the magnitude of stress responses did not vary with social status. The increase in monocyte- and leukocyte-platelet aggregates was associated with systolic blood pressure stress responsivity. CONCLUSIONS: Psychological stress induces platelet activation as indexed by leukocyte-platelet aggregates, and correlations with cardiovascular stress reactions suggest that sympathoadrenal responses may be responsible. Platelet activation may be a mechanism through which social position influences cardiovascular disease risk.

Distribution of melatonin MT1 receptor immunoreactivity in human retina.

Melatonin is synthesized in the pineal gland and retina during the night. Retinal melatonin is believed to be involved in local cellular modulation and in regulation of light-induced entrainment of circadian rhythms. The present study provides the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT1) in human retina of aged subjects. Ganglion, amacrine, and photoreceptor cells expressed MT1. In addition, MT1 immunoreactivity was localized to cell processes in the inner plexiform layer and to central vessels of the retina, as well as to retinal vessels but not to ciliary or choroidal vessels. These results support a variety of cellular and vascular effects of melatonin in the human retina. Preliminary evidence from patients with Alzheimer's disease (AD) revealed increased MT1 immunoreactivity in ganglion and amacrine cells, as well as in vessels. In AD cases photoreceptor cells were degenerated and showed low MT1 expression.

Exaggerated platelet and hemodynamic reactivity to mental stress in men with coronary artery disease.

OBJECTIVE: This study compared the effects of acute mental stress on cardiovascular and subjective responses and platelet activation in male patients with established coronary artery disease (CAD) and age-matched controls. METHODS: We assessed 17 male CAD patients aged 44 to 59 years and 22 healthy male controls. Blood pressure, heart rate, and hemodynamics were assessed before, during, and up to 2 hours after administration of color/word and mirror tracing tasks. Blood was sampled at baseline, after tasks, and at 30 and 75 minutes after stress, and platelet activation was assessed by measuring platelet-leukocyte aggregates (PLAs) using flow cytometry. RESULTS: CAD patients showed significantly greater systolic blood pressure stress responses than controls (mean increases of 43.9 and 28.3 mm Hg, adjusted for income, body mass index, waist/hip ratio, and medication), together with larger increases in heart rate (14.1 and 4.7 bpm) and cardiac index. Total peripheral resistance increased during the poststress recovery period in CAD patients but not in controls. PLAs increased with stress in both groups, but remained elevated at 75 minutes in CAD patients, returning to baseline in controls. Heart rate and cardiac index responses were correlated with increases in subjective stress and with depression ratings, whereas PLA responses were associated with ratings of task difficulty. CONCLUSION: Acute mental stress stimulated heightened cardiovascular responses in CAD patients, coupled with more prolonged platelet activation. These factors may contribute to plaque rupture and thrombogenesis, and partly mediate stress-induced triggering of acute coronary syndromes.

Loneliness and neuroendocrine, cardiovascular, and inflammatory stress responses in middle-aged men and women.

Loneliness is a psychological experience related to social isolation and perceived lack of companionship, and may be relevant to health risk. The revised UCLA loneliness scale was completed by 240 working men and women aged 47-59 years, and related to affective state and neuroendocrine, cardiovascular, and inflammatory responses. Loneliness scores were not associated with gender, age or socioeconomic position, but were lower in married than single or divorced participants, and were positively related to social isolation, low emotional support, ratings of depression, hopelessness and low self-esteem, and to reported sleep problems. Diastolic blood pressure reactions to acute mental stress were positively correlated with loneliness in women but not men, independently of age, socioeconomic status, smoking, body mass and marital status (p = 0.014). Lonely individuals also displayed significantly greater fibrinogen (p = 0.038) and natural killer cell responses (p = 0.042) to stress, independently of covariates. The cortisol response over the first 30 min following waking was positively associated with loneliness after adjusting for waking cortisol value, sex, socioeconomic status, smoking, time of waking, and body mass (p = 0.046). We conclude that loneliness is a psychological experience with potentially adverse effects on biological stress processes that may be relevant to health.

Differential expression of high-affinity melatonin receptors (MT1) in normal and malignant human breast tissue.

Melatonin is a pineal hormone that strongly inhibits the growth of breast cancer cells in vitro and in vivo. We report thefirst use of immunohistochemical analysis to determine the distribution of the high-affinity melatonin receptor subtype, MTI, in human breast tissue, the hypothalamic suprachiasmatic nucleus, and skin. The MT1 antibody, which is specific for the cytoplasmic portion of the receptor, produced cytoplasmic staining in normal-appearing breast epithelial cells and ductal carcinoma cells; stromal cells, myoepithelial cells, and adipocytes were nonreactive. The majority of nonneoplastic samples (13/19 [68%]) were negative to weakly positive, while moderate to strong reactivity was seen in most cancer samples (49/65 [75%]). Thus, although MT1 receptors were detectable in normal and malignant breast epithelium, high receptor levels occurred more frequently in tumor cells (P < .001), and tumors with moderate or strong reactivity were more likely to be high nuclear grade (P < .045). These findings may have implications for the use of melatonin in breast cancer therapy.

Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women.

Loneliness is a predictor of mortality and increased cardiovascular morbidity. Inflammation is a potential pathway through which loneliness might impact health. The aim of the study was to investigate the relationship between loneliness and inflammatory interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra) and monocyte chemotactic protein-1 (MCP-1) responses to standardized mental stress. A secondary purpose was to evaluate whether individual variations in cortisol responses influenced the hypothesised relationship between loneliness and inflammation. Saliva samples and blood were taken from 524 healthy middle-aged men and women from the Whitehall II cohort at baseline, immediately after the stress tasks and 45min later. Loneliness was measured using the revised UCLA loneliness scale. Greater loneliness was associated with larger IL-6 (p=0.044) and IL-1Ra (p=0.006) responses to psychological stress and higher MCP-1 (p<0.001) levels in women, independently of age, grade of employment, body mass index and smoking status. No associations were observed in men. Cortisol responsivity was inversely related to loneliness in women, with the odds of being a cortisol responder decreasing with increased loneliness independently of covariates (p=0.008). The impact of loneliness on health in women may be mediated in part through dysregulation of inflammatory and neuroendocrine systems.

Hostility and cellular aging in men from the Whitehall II cohort.

BACKGROUND: Hostility is associated with a significantly increased risk of age-related disease and mortality, yet the pathophysiological mechanisms involved remain unclear. Here we investigated the hypothesis that hostility might impact health by promoting cellular aging. METHODS: We tested the relationship between cynical hostility and two known markers of cellular aging, leukocyte telomere length (TL) and leukocyte telomerase activity (TA), in 434 men and women from the Whitehall II cohort. RESULTS: High-hostile men had significantly shorter leukocyte TL than their low-hostile counterparts. They also had elevated leukocyte TA, with a significantly increased likelihood of having both short TL and high TA, compared with low-hostile individuals. CONCLUSIONS: Because telomerase is known to counteract telomere shortening by synthesizing telomeric DNA repeats, particularly in the context of shortened telomeres, heightened TA might represent a compensatory response in high-hostile individuals. The relationship between hostility and disease is stronger in men than in women, and men generally have a shorter life expectancy than women. Our findings suggest that telomere attrition might represent a novel mechanism mediating the detrimental effects of hostility on men's health.

Adiposity, leptin and stress reactivity in humans.

Evidence suggests that individuals who are more obese may be more responsive to stress. Stress activates the sympathetic nervous system (SNS) and the adipose-tissue cytokine leptin stimulates SNS activity in animals. We examined the relationship between adiposity, leptin and physiological responses to acute laboratory stress in 67 women. We predicted that individuals with greater adiposity and/or higher plasma leptin would be more stress-responsive. Adiposity was unrelated to cardiovascular or neuroendocrine stress reactivity. However, women with larger waists had greater stress-induced increases in plasma leptin and interleukin-1 receptor antagonist (IL-1Ra). Similarly, women with higher basal leptin displayed greater stress-induced increases in heart rate and plasma interleukin-6, and larger decreases in heart rate variability and cardiac pre-ejection period. Heightened cardiovascular and inflammatory stress responses are predictive of future cardiovascular risk. Our findings suggest that the cytokines leptin and IL-1Ra may play a role in the association between obesity, stress and cardiovascular health.