Edward C. Suarez

Situational determinants of cardiovascular and emotional reactivity in high and low hostile men.

&NA; Various epidemiologic studies have found that high scores on the Cook and Medley Hostility (Ho) scale are associated with increased risk of coronary heart disease (CHD), severity of atherosclerosis, and all‐cause mortality. One plausible biological mechanism suspected of contributing to increased risk of CHD is sympathetic nervous system‐mediated hyperresponsivity to environmental stressors. The present study evaluated cardiovascular reactivity among young men with high versus low Ho scores during performance of an anagram task with or without harassment. Compared to performing the task alone, harassment led to increased cardiovascular arousal that was more pronounced for the high Ho subjects than the low Ho subjects. Moreover, harassment produced increases in self‐rated anger, irritation, and tension, but it was only among those subjects with high Ho scores that increased anger and irritation were associated with enhanced cardiovascular arousal. While suggesting a role for anger‐ and irritation‐induced cardiovascular arousal in pathogenesis of CHD, these findings indicate that situation characteristics mediate the relationship between Ho scores and cardiovascular reactivity, and that there may be a differential biological link between anger/irritation and cardiovascular responses in men with high and low Ho scores.

NEUROENDOCRINE, CARDIOVASCULAR, AND EMOTIONAL RESPONSES OF HOSTILE MEN : THE ROLE OF INTERPERSONAL CHALLENGE

Objective We examined the effects of hostility and harassment on neuroendocrine, cardiovascular, and emotional responses in 52 healthy white men. Methods Subjects were preselected on the basis of scores in the top and bottom quartiles (above 23 and below 15, respectively) on the Cook and Medley Hostility (Ho) scale. Subjects participated in a solvable anagram task. Thirty subjects were harassed by the technician during the task. Results Harassed subjects with high Ho scores exhibited enhanced and prolonged blood pressures, heart rate, forearm blood flow, forearm vascular resistance, norepinephrine, testosterone, and cortisol responses relative to low-Ho subjects in the harassed condition and high and low-Ho subjects in the nonharassed condition. Heightened physiological reactivity in high-Ho subjects was correlated with arousal of negative affects. Conclusions The findings are consistent with the general hypothesis that high hostile men show excessive behaviorally-induced cardiovascular and neuroendocrine responsivity to interpersonal challenging situations. Moreover, in high-Ho men, the stress-induced cardiovascular and neuroendocrine hyperreactivity is associated with the arousal of negative affects such as anger.

Serotonin-Related Gene Polymorphisms and Central Nervous System Serotonin Function *

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover—indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)—in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity×genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender×genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

The relationships between dimensions of hostility and cardiovascular reactivity as a function of task characteristics

&NA; The present study examined the independent relationships between dimensions of hostility and cardiovascular responses to a laboratory task with and without harassment. Fifty‐three males, aged 18 to 26, with a negative parental history of cardiovascular disease were selected on the basis of their scores on the Cook and Medley Hostility (Ho) scale (greater than 24 or less than 14). Factor‐analysis of six separate measures of hostility/anger resulted in a two‐factor solution; Factor 1 representing antagonistic hostility and Factor 2 representing neurotic hostility. Results showed that high factor scores on antagonistic hostility were significantly associated with greater systolic blood pressure (SBP) and forearm blood flow (FBF) changes and poorer SBP recovery to harassment. In addition, high factor scores on neurotic hostility significantly predicted greater FBF changes to harassment. Additional correlational analysis showed that cardiovascular responses were positively associated with self‐reported negative affects but only for subjects with high scores on either dimension. These results are in agreement with recent evidence suggesting that only antagonistic hostility may be related to increased severity of coronary artery disease and that the degree of interpersonal conflict moderates the association between coronary‐prone behaviors and cardiovascular responses.

Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity.

Self-reported ratings of sleep quality and symptoms of poor sleep have been linked to increased risk of coronary heart disease (CHD), Type 2 diabetes and hypertension with recent evidence suggesting stronger associations in women. At this time, the mechanisms of action that underlie these gender-specific associations are incompletely defined. The current study examined whether gender moderates the relation of subjective sleep and sleep-related symptoms to indices of inflammation, coagulation, insulin resistance (IR) and psychosocial distress, factors associated with increased risk of cardiovascular and metabolic disorders. Subjects were 210 healthy men and women without a history of sleep disorders. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and frequency of sleep symptoms. In multivariate-adjusted models, overall poor sleep quality, more frequent problems falling asleep (>2 night/week) and longer periods to fall asleep (>30 min) were associated with greater psychosocial distress, higher fasting insulin, fibrinogen and inflammatory biomarkers, but only for women. The data suggest that subjective ratings of poor sleep, greater frequency of sleep-related symptoms, and longer period of time to fall asleep are associated with a mosaic of biobehavioral mechanisms in women and that these gender-specific associations have direct implications to recent observations suggesting gender differences in the association between symptoms of poor sleep and cardiovascular disease.

Enhanced expression of cytokines and chemokines by blood monocytes to in vitro lipopolysaccharide stimulation are associated with hostility and severity of depressive symptoms in healthy women.

The current study investigated the relation of hostility and severity of depressive symptoms, separately and jointly, to the capacity of blood monocytes to secrete an array of cytokines when stimulated by bacterial lipopolysaccharide (LPS). Subjects were 44 healthy, non-smoking, premenopausal women (aged 23-49 years) not currently taking oral contraceptives. Data were collected during the follicular phase of the menstrual cycle. The Cook-Medley Hostility (Ho) scale and the Beck Depression Inventory (BDI) were used to assess hostility and severity of depressive symptoms, respectively. Dual-color flow cytometry was used to measure the total expression of interleukin (IL)-1alpha, IL-1beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1 and monocyte inflammatory protein (MIP)-1alpha in blood monocytes following 4 h in vitro LPS stimulation of whole blood. In analyses adjusting for age, body mass index (BMI), fasting cholesterol, alcohol use, race and 17beta-estradiol (E(2)), higher Ho scores were associated with greater LPS-stimulated expression of IL-1alpha (beta = 0.033, p = 0.02), IL-8 (beta = 0.046, p = 0.01) and IL-1beta (beta = 0.024, p = 0.06). Higher BDI scores were associated with greater expression of TNF-alpha (beta = 0.042, p = 0.02) and IL-8 (beta = 0.045, p = 0.04). The linear combination of Ho and BDI scores was significantly associated with IL-1beta (beta = 0.18, p = 0.057), IL-8 (beta = 0.36, p = 0.01), TNF-alpha (beta = 0.25, p = 0.03), and IL-1alpha (beta = 0.18, p < 0.07). Thus, in healthy women, these psychological risk factors, alone and in combination, induce a proinflammatory phenotype in circulating monocytes characterized by the up-regulation of proinflammatory cytokines, supporting the hypothesis that inflammation may be a key pathway whereby hostility and depressive symptoms contribute to atherosclerosis and subsequent coronary heart disease (CHD).

Central nervous system serotonin function and cardiovascular responses to stress.

Objective The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. Methods Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. Results Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. Conclusions These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.

C-reactive protein is associated with psychological risk factors of cardiovascular disease in apparently healthy adults.

Objective: The current study examined the relation of anger, hostility, and severity of depressive symptoms, alone and in combination, to C-reactive protein (CRP) in healthy men and women. Methods: A high sensitivity enzyme linked immuno sorbent assay (ELISA) was used to evaluate CRP levels in a multiethnic sample of 127 healthy, nonsmoking men and women. Fasting blood samples were collected the same day the assessments were done of anger and hostility using the Buss-Perry Aggression Questionnaire (BPAQ) and depressive symptomatology using the Beck Depression Inventory (BDI). A psychological risk factor (PRF) score representing a composite summary indicator of BDI and BPAQ-anger and -hostility was generated using principal component analysis. Log-transformed CRP values were examined using univariate and multivariate analyses adjusting for control variables of age, gender, body mass index (BMI), alcohol use, exercise frequency, ratio of total to high-density lipoprotein cholesterol, and family history of premature coronary heart disease (CHD). Results: Log-normalized CRP was correlated with BDI (r = 0.21, p = .02) and BPAQ anger (r = 0.20, p = .02), but not with BPAQ hostility. After adjustment for control variables, BDI (&bgr; = 0.05, p = .011), BPAQ anger (&bgr; = 0.05, p = .007), and the PRF composite score (&bgr; = 0.27, p = .005), but not BPAQ hostility (&bgr; = 0.03, p = .11), were significantly associated with log-normalized CRP. Conclusions: Greater anger and severity of depressive symptoms, separately and in combination with hostility, were significantly associated with elevations in CRP in apparently healthy men and women. These associations were independent of potential confounding factors. BDI = Beck Depression Inventory; BMI = body mass index; BPAQ = Buss-Perry Aggression Questionnaire; CHD = coronary heart disease; CVD = cardiovascular disease; ELISA = enzyme linked immuno sorbent assay; hsCRP = high sensitivity C-reactive protein; IL = interleukin; MCP-1 = monocyte chemoattractant protein-1; MI = myocardial infarction; MIP-1a = monocyte inflammatory protein-1a; NHANES III = Third National Health and Nutrition Examination Survey; OTC = over-the-counter; PRF = psychological risk factor; TNF-&agr; = tumor necrosis factor-&agr;.

Stress and lipoprotein metabolism: Modulators and mechanisms

Abstract Elevated concentrations of triglycerides and low-density lipoprotein (LDL) cholesterol,1 especially in combination with low concentrations of high-density lipoprotein (HDL) cholesterol,2 are associated with an increased risk of atherosclerosis, coronary heart disease, and stroke. While several dietary and genetic factors contribute to atherogenic lipoprotein profiles,3,4 stress also contributes to unfavorable concentrations of lipoproteins that may predispose to cardiovascular disease.5,6 This report reviews the data supporting a link between stress and lipid metabolism, with particular focus on the mechanisms whereby stress could be related to increased lipid concentrations, and several factors which could modulate a relationship between stress and lipid levels. Following a brief discussion of stress, this report is divided into three main sections. First, data that support a relationship between stress and lipoprotein metabolism are considered. Data from laboratory studies, studies of episodic and chronic stress, studies on personality, and experiments from the animal literature are reviewed. The second major section discusses mechanisms that could account for stress effects on lipoprotein metabolism. This section considers the metabolic effects of stress, the effects of stress on hemoconcentration, and behavioral responses to stress that could affect lipid concentrations. The final major section reviews various modulators of the stress-lipid relationship, including intervening personality variables, gender, diet, seasonal variations in lipoprotein concentrations, and genetics and polymorphism. The concluding comments in this review address several promising areas for further research.

Stress in Employed Women: Impact of Marital Status and Children at Home on Neurohormone Output and Home Strain

Objective To evaluate the biological and psychological effects of role overload, we examined the effects of marital (or partnership) status and parental status (defined as having children at home) on daily excretion of urinary catecholamines and cortisol in a sample of 109 employed women. Other measures included work and home strain, and social support. Methods Urine collection was conducted on two consecutive workdays in three separate aliquots, a) overnight, b) daytime, and c) evening. Repeated-measures analysis of covariance with age and caffeine consumption as covariates was conducted on levels of epinephrine, norepinephrine, and cortisol in the three aliquots averaged across the 2 days. Results We found a significant main effect of parental status on 24-hour cortisol excretion, (p<.01) such that women with at least one child living at home excreted significantly more cortisol, independent of marital status or social support. Women with children at home also reported higher home strain (p<.001) but not work strain. A significant period of day effect for catecholamine levels was found (norepinephrine, p<.001; epinephrine, p<.0001) with all subjects showing an increase during the workday and little or no decline in levels during the evening. Catecholamine levels were unrelated to marital status, parental status, or social support. Conclusions These findings indicate that working women with children at home, independent of marital status or social support, excrete greater amounts of cortisol and experience higher levels of home strain than those without children at home.