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Vaping has increased 13-fold from 2011 to 2018 among adolescents in the United States (Cullen et al., 2018). Although marketed as a safer alternative, vaping, or electronic-cigarette (e-cigarette) use, is still associated with serious physical health problems (Masso-Silva et al., 2021; Sharma et al., 2021; Ween et al., 2021). Given increasing prevalence rates, more research on predictors of adolescent vaping is needed for targeted prevention efforts. Regulation indicators, such as self-control, impulsivity, and sensation seeking, have been established as reliable and robust correlates of use and misuse of other substances (e.g., alcohol) among adults, adolescents, and young children (e.g., Herman & Duka, 2019; Watts et al., 2020). Given that e-cigarettes are a relatively recent product, little research has comprehensively examined whether these individual regulation factors are also associated with vaping. Of the research that has investigated such factors, studies have been limited by cross-sectional designs or the use of single measures. For example, one cross-sectional study (N = 225) found that emotion dysregulation mediated the association between impulsivity (specifically negative urgency) and nicotine vaping susceptibility (not use) among undergraduate students (Reff & Baschnagel, 2021). Another cross-sectional study (N = 708) found that e-cigarette use was positively associated with sensation seeking and negatively associated with a self-regulation composite (Burnell et al., 2021). In addition, one longitudinal study (N = 137) found that lack of premeditation and sensation seeking from the UPPS scale was associated with e-cigarette use (including nicotine and cannabis), and negative urgency was negatively associated with use, over 21 months among participants aged 18-24 years (Mittal et al., 2022). The present study aims to extend this literature in four ways. First, we will draw on data from a large, longitudinal, and diverse sample of young community children (Time 1 [T1] N = 2,104; Mage = 12.36 years; Time 4 [T4] N = 891). Self-regulation and sensation seeking will be assessed from T1 through T4 and vaping will be assessed at T4. Second, we will use a multi-measurement approach for assessing self-regulation (including measures of self-regulation, self-control, effortful control, and impulsivity; Davisson et al., 2021). Third, we will employ latent class growth models to delineate the interplay between self-regulation and sensation seeking across adolescent development. Finally, we will examine the impact of different patterns of self-regulation and sensation seeking across adolescent development on two different types of vaping (nicotine and cannabis) controlling for adolescent age, gender, race/ethnicity, and socioeconomic status.

Substance Use Disorders present a major public health burden to both patients and the US society, costing more than $400 billion annually in associated crime, poor health outcomes, and lost productivity (Substance Abuse and Mental Health Services Administration (US), 2016). Use of alcohol or drugs at a young age is a strong predictor of substance dependency and regular substance use by late adolescence and adulthood (Jordan & Andersen, 2017). Although adolescents aged 15–17 are most likely to experiment with drugs and alcohol, initiation at a younger age is associated with the highest risk of developing abuse or dependence later in life (Jordan & Andersen, 2017). Thus, understanding the factors associated with early age onset of substance use is of critical importance. Growing evidence suggests that experiencing psychological stress during childhood may increase addiction vulnerability (Sinha, 2008). Though there are several hypotheses relating physiological and emotional stress to substance use susceptibility, little is known about the extent to which hair cortisol, a biomarker of chronic stress, contributes to substance use initiation. The present study aims to examine the relationship between HCC and substance use initiation, while controlling for chronic stress factors that are known to be related to substance use: SES, stressful life events, daily stressors, perceived discrimination, and perceived distress. By including both self-reports of stress and psychological distress and objective measures of SES, this project will advance our knowledge of how well HCC predicts substance use initiation above and beyond sources of psychological stress known to be associated with substance use. This knowledge will have important implications for clinicians who need to accurately identify children at greatest risk of early onset substance use in order to target interventions most efficiently and effectively.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy populations have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p

OBJECTIVES: Central nervous system (CNS) serotonin (5-HT) exerts both excitatory and inhibitory effects on the sympathetic nervous system (SNS) in animals. In this study, we examine the effects of tryptophan enhancement and depletion on plasma catecholamine levels in humans. METHODS: The total sample consisted of 164 healthy men and women who were tested over 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and eighty-five to a tryptophan depletion condition. Both protocols consisted of a “sham-day” followed by an “active-day”. Blood samples for assessment of plasma norepinephrine and epinephrine levels were collected prior and post tryptophan enhancement/depletion. Data were analyzed using general linear models. Separate analyses were conducted for each study arm and for each measure. RESULTS: In the depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and norepinephrine (F(5,335) = 2.79, p =.018) showed small increases on active vs ‘sham’ depletion days. There were also significant day X time interactions for epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked increase in epinephrine (Pre(mean =)23.92±12.23 vs. Post(mean =)81.57±62.36) and decrease in norepinephrine (Pre(mean =)257.2±106.11 vs. Post(mean =)177.04±87.15 ) whereas levels of both catecholamines were stable on the “sham-day”. CONCLUSIONS: CNS 5-HT exerts both inhibitory and excitatory effects on SNS activity in humans, potentially due to stimulation of CNS 5-HT receptors that have shown to have inhibitory (5-HT(1A)) and excitatory (5-HT(1A) and/or 5-HT(2)) SNS effects in animal models.

The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive treatment effects in schizophrenia clinical trials, and is considered the FDA gold standard outcome measure for that purpose. The aim of the present study was to establish pre-treatment psychometric characteristics of the MCCB in a large pooled sample. The dataset included 2616 stable schizophrenia patients enrolled in 15 different clinical trials between 2007 and 2016 within the United States (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of treatment in 1908 patients. Test-retest reliability and practice effects of the cognitive composite score, the neurocognitive composite score, which excludes the domain Social Cognition, and the subtests/domains were examined using Intra-Class Correlations (ICC) and Cohen's d. Simulated regression models explored which domains explained the greatest portion of variance in composite scores. Test-retest reliability was high (ICC=0.88) for both composite scores. Practice effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17) composites. Simulated bootstrap regression analyses revealed that 3 of the 7 domains explained 86% of the variance for both composite scores. The domains that entered most frequently in the top 3 positions of the regression models were Speed of Processing, Working Memory, and Visual Learning. Findings provide definitive psychometric characteristics and a benchmark comparison for clinical trials using the MCCB. The test-retest reliability of the MCCB composite scores is considered excellent and the learning effects are small, fulfilling two of the key criteria for outcome measures in cognition clinical trials.

Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits.The purpose of this study is to determine whether central nervous system serotonin influences the association between hostility and fasting glucose in African American women.The study consisted of 119 healthy volunteers (36 African American women, 27 White women, 21 White males, and 35 African American males, mean age 34 ± 8.5 years). Serotonin related compounds were measured in cerebrospinal fluid. Hostility was measured by the Cook-Medley Hostility Scale.Hostility was associated with fasting glucose and central nervous system serotonin related compounds in African American women only. Controlling for the serotonin related compounds significantly reduced the association of hostility to glucose.The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

Introduction Blunted nighttime blood pressure (BP) dipping is prognostic of cardiovascular morbidity and mortality. Patients with coronary heart disease (CHD) are often characterized by a blunted nighttime BP dipping pattern. The present study compared the effects of 2 behavioral intervention programs, aerobic exercise (EX) and stress management (SM) training, with a usual care (UC) control group on BP dipping in a sample of CHD patients. Methods This was a secondary analysis of a randomized, controlled trial with allocation concealment and blinded outcome assessment in 134 patients with stable CHD and exercise-induced myocardial ischemia. Nighttime BP dipping was assessed by 24-hour ambulatory BP monitoring, at prerandomization baseline and after 16 weeks of one of the following treatments: usual medical care; UC plus supervised aerobic EX for 35 minutes, 3 times per week; UC plus weekly 1.5-hour sessions of SM training. Results The EX and SM groups exhibited greater improvements in systolic BP dipping ( P =.052) and diastolic BP dipping ( P =.031) compared with UC. Postintervention systolic BP percent-dipping means were 12.9% (SE=1.5) for SM, 11.1% (SE=1.4) for EX, and 8.6% (SE=1.4) for UC. Postintervention diastolic BP percent-dipping means were 13.3% (SE=1.9) for SM, 14.1% (SE=1.8) for EX, and 8.8% (1.8) for UC. Conclusions For patients with stable CHD, EX or SM training resulted in improved nighttime BP dipping compared with usual medical care. These favorable effects of healthy lifestyle modifications may help reduce the risk of adverse clinical events.

Aims—We examined whether the relationship between anxiety and indicators of glucose metabolism in people without diabetes varies by race and gender. Methods—Participants were 914 adults (777 white, 137 black) without diabetes in the MIDUS II study. Glucose metabolism was characterized by fasting glucose, insulin, HOMA-IR, and HbA1c. Hierarchical linear regressions stratified by race and gender examined whether anxiety was associated with glucose metabolism. Results—After adjustment for potential confounders, positive relationships between anxiety and fasting glucose (p=.04), insulin (p=.01), and HOMA-IR (p=.02) but not HbA1c, were observed in black women only. Conclusions—Our findings extend prior evidence about the links between psychosocial vulnerabilities and impaired glucose metabolism in black women, by documenting significant associations between anxiety and clinical indicators of glycemic control among black women without diabetes. Thus, anxiety might constitute an intervention target in black women, a subgroup disproportionately affected by type 2 diabetes, its complications, and premature mortality.

Objective: To use measures of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and genotype of a functional polymorphism of the monoamine oxidase A gene promoter (MAOA-uVNTR) to study the role of central nervous system (CNS) serotonin in clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes. Methods: In 86 healthy male volunteers, we evaluated CSF levels of the primary serotonin metabolite 5HIAA and MAOA-uVNTR genotype for association with a panel of 29 variables assessing hostility, other psychosocial, metabolic, and cardiovascular endophenotypes. Results: The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those of men with less active alleles for 15 of the 29 endophenotypes. MAOA-uVNTR genotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, body mass index, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles. Conclusions: These findings indicate that, in men, indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, whereas decreased CNS serotonin function is associated with a less favorable profile.

OBJECTIVE To examine whether the relationship of hostility (HOST) to fasting glucose indices is moderated by sex and race. HOST has been associated with abnormalities in glucose metabolism. Prior studies suggested that this association may be more prevalent in women and in African American (AA) individuals. METHODS A total of 565 healthy AA and white (W) men and women (mean age = 33 +/- 6 years) were assessed. HOST was measured by the 27-item version of the Cook Medley HOST Scale. The moderating effects of sex and race were evaluated for the associations of HOST to fasting glucose, insulin, and insulin sensitivity (HOMA-IR). RESULTS Analysis showed a moderating effect of sex and race on the association of HOST to fasting glucose (p = .03), but not for insulin (p = .12). Analysis of HOMA-IR revealed a trend (p = .06) for the interaction. Stratified analyses by race and sex revealed a positive association between HOST and fasting glucose only in AA women, which remained significant after controlling for age and body mass index. CONCLUSION A relationship between HOST and fasting glucose was evident in AA women only, a group that has twice the risk of developing Type 2 diabetes compared with W women. Further studies are needed to elucidate the mechanisms by which HOST may affect glucose metabolism in AA women.

Background Although a number of epidemiological studies have found an association between socioeconomic status (SES) indices such as income and education and coronary morbidity and mortality, few have looked at health consequences arising from actually experiencing financial shortcomings. The objective of the present study was to examine whether financial strain predicts recurrent coronary artery disease (CAD) events among women with established CAD. Methods Two hundred two women (mean age 62±9 years) hospitalized for an acute coronary event were followed over a period of 3.5 years. Demographic, socioeconomic, lifestyle-related, psychosocial and biological characteristics were obtained by means of questionnaires and clinical examination. Data on recurrent cardiac events were collected from the Swedish discharge and death registers. Results Women experiencing financial strain over the past year had an increased risk for recurrent events, i.e. the combination of all-cause mortality, new acute myocardial infarction and unstable angina pectoris during the follow-up with an unadjusted hazard ratio (HR) of 3.2 (95% CI 1.6–6.6), and a HR of 2.76 (95% CI 1.02–7.50) after controlling for education, household income, age, cohabiting status, inclusion diagnosis and rehabilitation therapy. Adjustment for potential mediators, i.e. psychosocial factors, lipids, diabetes mellitus, smoking, body-mass index, blood pressure, physical activity, alcohol consumption, participation in other cardiac rehabilitation programs did not alter the results significantly. Conclusions Financial strain was a predictor for recurrent events among women with CAD, independently of commonly used SES indicators such as education and household income. Future studies will have to explore the mechanism behind this association.

Background: n−3 (omega-3) Fatty acids are associated with a reduced risk of cardiovascular disease; however, the relation between dietary intake of n−3 fatty acids and ventricular arrhythmias has not been investigated among acute post-myocardial infarction (AMI) patients—a group at elevated risk of malignant arrhythmias. Objective: The objective was to examine the association between n−3 fatty acid consumption and ventricular ectopy among AMI patients. Design: In 260 AMI patients, dietary intake of n−3 fatty acids was assessed by using the Harvard food-frequency questionnaire, and ventricular ectopy was estimated from 24-h electrocardiograph recordings. Results: A greater intake of n−3 fatty acids (eicosapentaenoic acid + docosahexaenoic acid + docosapentaenoic acid + α-linolenic acid) was associated with lower ventricular ectopy (β = −0.35, P = 0.011), and this effect remained after cardiovascular comorbidities were controlled for (β = −0.47, P = 0.003). Higher concentrations of both marine-based (eicosapentaenoic acid + docosahexaenoic acid) (β = −0.21, P = 0.060) and plant-based (α-linolenic acid) (β = −0.33, P = 0.024) fatty acids remained associated with lower ventricular ectopy after cardiovascular comorbidities were controlled for. Conclusion: These findings extend existing evidence linking n−3 fatty acid consumption to a reduced risk of ventricular arrhythmias by showing that a greater intake of n−3 fatty acids may be associated with low ventricular ectopy among AMI patients.

Work and marital status have been shown to be associated with health outcome in women. However, the effect of employment and marriage on psychosocial functioning has been studied predominantly in healthy subjects. We investigated whether work and marital status are associated with depressive symptoms, social support, and daily stress behavior in women with coronary artery disease (CAD).Data of 105 women with CAD and of working age were analyzed. General linear models were used to determine the association between work and marital status and depressive symptoms, social support, and daily stress behavior.Women who were working at the time of measurement had lower levels of depressive symptoms (7.0 +/- 1.2 vs. 12.1 +/- 0.9, p0.01) and higher levels of social support (21.6 +/- 1.0 vs. 18.9 +/- 0.7, p = 0.03) than the nonworking women, whereas marital status was not related to any of the outcome variables. Results were similar after adjusting for potential confounders, that is, age, education, self-reported health, and risk factors for CAD. There was no significant interaction between marital status and working status on depressive symptoms, social support, or daily stress behavior.In women with CAD, all65 years of age, after a cardiac event, patients working had lower levels of depressive symptoms and a better social integration than those not working, regardless of reason for being nonemployed. Daily stress behavior, depression, and social support did not differ between cohabiting and not cohabiting women. Future interventions should take into consideration that women with CAD who are unemployed may have a higher risk for depression and social isolation and, therefore, poor clinical outcomes.

OBJECTIVE—This study examined the associations of depressive symptoms with glucose concentrations and morning cortisol levels in 665 African-American and 4,216 Caucasian Vietnam-era veterans. RESEARCH DESIGN AND METHODS—Glucose level was measured as a three-level variable (diabetes, impaired glucose, and normal). Depressive symptoms were measured by the Obvious Depression Scale (OBD) from the Minnesota Multiphasic Personality Inventory. RESULTS—Regression models showed significant race × OBD interactions in relation to glucose concentration (P < 0.0001) and cortisol (P < 0.0001). The OBD was positively associated with glucose concentration and cortisol in both racial groups. However, the magnitude of those associations was larger for African Americans. Further analyses suggested that cortisol partially mediated the race difference in the relation of depressive symptoms to glucose concentrations. CONCLUSIONS—These results suggest that enhanced hypothalamic pituitary adrenal activity plays an important role in the relation of depressive symptoms to dysregulated glucose metabolism and may partially explain the differential effects of depressive symptoms on glucose levels in African-American and Caucasian male subjects.

Background Although psychologic stress has been implicated in the pathogenesis of ventricular arrhythmias, the relationship between self-reported stress and ventricular ectopy has not been evaluated under naturalistic conditions in acute post–myocardial infarction (MI) patients, a group at elevated risk for arrhythmias. Materials and Methods Diary-reported stress was measured during 24-hour Holter monitoring in 80 patients (52 men and 28 women) approximately 12 weeks after their MI. In addition, state and trait anxiety were measured using the Spielberger State and Trait Anxiety Inventory, which was administered at the beginning of the 24-hour Holter monitoring session. The relationships between diary-reported stress, anxiety, and ventricular ectopy were evaluated. Results Mean diary-reported stress was associated with total ventricular ectopy ( β = .29, P = .01). State anxiety was also associated with 24-hour ectopy ( β = .24, P = .04); however, trait anxiety was not significantly associated with ectopy. Temporal analyses of the relationship between stress and ectopy showed that diary-reported stress was associated with an increase in the number of ventricular premature beats occurring in the following hour ( β = .74, P Conclusions These findings extend existing evidence linking psychologic factors to ventricular arrhythmias by demonstrating that psychologic stress predicts increased arrhythmic activity during routine daily activities in post-MI patients.

Background While aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. Methods and Results We used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P =1.3×10 −5 ), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen. Conclusions Together, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐ COX 1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.

Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive protein (CRP).Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay.Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study.Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.

Although heat shock proteins (Hsp’s) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure >95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBMmax) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8,P=0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11,P=0.10). There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.

Despite recent advances in the medical management of hypertension, chronically elevated blood pressure remains a major health problem in the United States, affecting almost 50 million Americans. It is widely recognized that lifestyle factors contribute to the development and maintenance of elevated blood pressure. This article critically reviews current approaches to the nonpharmacological treatment of high blood pressure and highlights outcome studies of exercise, weight loss and dietary modification, and stress management and relaxation therapies. Methodological issues in the assessment and treatment of hypertension are discussed, along with possible mechanisms by which lifestyle modification may reduce elevated blood pressure.

STEFFEN. P. R.. A. SHERWOOD. E. C. D. GULLETTE. A. GEORGIADES. A. HINDERLITER, and J. A. BLUMENTHAL. Effects of exercise and weight loss on blood pressure during daily life. Med. Sci. Sports Exerc.. Vol. 33, No. 10, 2001, pp. 1635-1640. Purpose: The objective of this study was to investigate the effects of exercise training and weight loss on blood pressure (BP) associated with physical activity and emotional stress during daily life. Methods: One hundred twelve participants with unmedicated high normal or stage I to stage 2 hypertension w%ere randomized to one of three conditions: a combined exercise and behavioral weight management group (WNI), an exercise-only group (EX). or a wait list control group (CON). BP was assessed in the clinic and during 15 h of daytime ambulatorv BP monitoring at baseline and after 6 months of treatment. Results: Increased levels of physical activity and emotional distress measured during daily life were associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP). heart rate (HR). and rate pressure product (RPP). After treatment, the WM group had significantly lower DBP. HR. and RPP responses during both high and low levels of physical activity and emotional distress compared with the CON group. The EX group had similar BP levels as the WM group. although the EX group had significantly lower BP than the CON group during low but not high levels of physical activity and emotional distress. Conclusion: These findings indicate that exercise. especially when combined with weight loss. reduces BP levels at rest and in situations that typically elevate BP such as intense physical activity and emotional distress. Key Words: STRESS. AMBULATORY MONITORING, PHYSICAL ACTIVITY, EMOTIONAL DISTRESS. AMBULATORY BLOOD PRESSURE

Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.

Exaggerated cardiovascular reactivity has been implicated in the development of left ventricular hypertrophy. The aim of the present study was to investigate the predictive value of casual clinic, ...

Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention Heart Study. Many metabolites, including known aspirin catabolites, changed on exposure to aspirin, and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Furthermore, purines were associated with aspirin response, and poor responders had higher postaspirin adenosine and inosine levels than did good responders (n = 76; both P < 4 × 10(-3)). Using our established "pharmacometabolomics-informed pharmacogenomics" approach, we identified genetic variants in adenosine kinase associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response--an important step toward personalized treatment approaches for cardiovascular disease.

Interindividual variability in response to antiplatelet therapy results in higher platelet reactivity as well as higher rates of cardiovascular events. Despite substantial effort, the genetic and nongenetic determinants of antiplatelet variability remain poorly understood. Emerging pharmacometabolomic paradigms that integrate systems approaches such as pharmacogenomics have the potential to unveil novel biology regarding disease pathogenesis, reveal the effect of drugs on pathways, and allow better understanding of response variability. Such approaches offer great potential for personalized antiplatelet treatment. Clinical Pharmacology & Therapeutics (2013); 94 5, 570–573. doi:10.1038/clpt.2013.153

Our primary aim in the present study was to investigate the association between blood pressure measured in the laboratory and in the ambulatory state in a group of middle-aged borderline hypertensive men and age-matched normotensive control subjects. In addition, we examined the relation between stress-induced blood pressure measurements and left ventricular mass. Blood pressure and heart rate were measured noninvasively during a standardized laboratory stress protocol and four times per hour throughout 24 hours. Borderline hypertensive subjects had significantly higher systolic and diastolic pressures than normotensive subjects during both the daytime (systolic pressure, 141.1±9.7 versus 130.9±8.6 mm Hg; diastolic pressure, 88.8±7.0 versus 79.4±6.2 mm Hg, P P r =.51 to .82). Furthermore, stress-induced blood pressure levels were significantly correlated to left ventricular mass in borderline hypertensive ( r =.33 to .40) but not normotensive subjects. Since stress-induced blood pressure levels were significantly associated with both ambulatory blood pressure levels and left ventricular mass in borderline hypertensive subjects, the addition of standardized stress testing to casual blood pressure measurements may improve risk estimation.

Cardiovascular disease (CVD) is the primary cause of death in Korea. Hyperhomocysteinemia confers an independent risk for CVD comparable to the risk of smoking and hyperlipidemia. The purpose of this study was to assess the effect of cardiovascular risk factors and body composition change on homocysteine (Hcy) levels in Korean men and women. The association between body composition and Hcy levels was investigated in a 2-yr prospective cohort study of 2,590 Koreans (mean age 45.5±9.6 yr). There were 293 cases of hyperhomocysteinemia (>14 µM/L) at follow-up. Increases in total body fat proportion and decreases in lean body mass (LBM) were significantly associated with increases in Hcy concentration after controlling for confounding factors. Further adjustments for behavioral factors showed that decreases in LBM were associated with Hcy increase. Decrease in LBM also predicted hyperhomocysteinemia at follow-up, after controlling for confounding factors. There was no significant association between change in body mass index (BMI) and Hcy concentrations over time. Hcy changes over time were related to change in LBM and body fat content, whereas BMI or weight change did not predict change in Hcy levels. Changes in ratio of LBM to total fat mass may contribute to hyperhomocysteinemia.

It has been suggested that the association between anthropometric measures of adiposity (e.g., waist circumference (WC) and body mass index (BMI)) and high blood pressure vary by race.1 These anthropometric measures, however, only broadly capture more complex underlying patterns of body composition and adiposity (e.g., visceral vs. subcutaneous adipose tissue, upper body vs. abdominal fat), which also vary by sex and race.2 Despite their relative lack of specificity with respect to adiposity, techniques for assessing anthropometric measures such as BMI and WC are comparatively inexpensive and widely accessible. Thus, further elucidation of how these relatively simple measures are associated with disease remains important. The present study describes the association between WC and systolic blood pressure (SBP), with a focus on how these relations may vary by race and sex, using a large nationally representative sample of young adults in the United States. We focus on SBP in the present study because, although associations have been shown to vary by age,3 many studies have shown SBP to be more important than diastolic blood pressure (DBP) with respect to health risk,4–9 and also possibly more responsive than DBP to changes in modifiable risk factors such as exercise, diet, and weight loss.10 WC has been shown to add to the prediction of visceral fat beyond measurements of BMI.11,12 Visceral adipose tissue is an independent predictor of the metabolic syndrome in both men and women,13 and has also been found to add to the prediction of hypertension.14,15 Following Tybor et al.,16 we use statistical partialling to remove the effect of BMI from the association between WC and SBP. WC partialled for BMI reflects WC independent of overall body size, and thus, by definition, must reflect body shape or body fat distribution. We also allow for the possibility that these associations may be nonlinear. Examination of these questions in this manner may provide more precise information about the pathophysiology underlying high blood pressure and also further guide risk stratification in clinical practice.

Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmogens. An earlier study found differences in plasma phospholipids between unmedicated patients with schizophrenia and matched healthy control subjects. We here report a comparison of plasma plasmalogen levels across 20 drug-naive patients experiencing first psychotic episodes, 20 recently unmedicated patients experiencing psychotic relapses after failing to comply with prescribed medications, and 17 matched healthy control subjects. Multiple plasma phosphatidylcholine and phosphatidylethanolamine plasmalogen levels were significantly lower in first episode patients and patients with recurrent disease compared to healthy controls. Reduced plasmalogen levels appear to be a trait evident at the onset of psychotic illness and after multiple psychotic relapses. It is implied that reductions in plasmalogen levels are not related to antipsychotic treatment but due to the illness itself. Reduced plasmalogen levels suggest impairments in membrane structure and function in patients with schizophrenia that might happen early in development. This may serve as a clue to the neurobiology of schizophrenia and should be studied as a potential biomarker for individuals at risk for schizophrenia.

The reliability of classically conditioned skin conductance responses was investigated. Temporal stability was determined in 28 subjects studied three weeks apart (study 1), and internal consistency in 223 subjects studied once (study 2). A discriminative classical conditioning paradigm using slides with a duration of 8 s served as conditioned stimuli (CS) for an aversive unconditioned noise stimulus (study 1) or a mild unconditioned electric shock stimulus (UCS) (study 2). Electrodermal responses were recorded during a habituation phase (4 trials), an acquisition phase, where CS+ was paired repeatedly with the UCS, while CS- never was (8 trials), and an extinction phase during which shocks were withheld (8 trials each). First interval responses were measured 1-4 s after CS- onset during all phases of the experiment. During the acquisition and extinction phases, second interval responses were scored 5-9 s after CS- onset while third interval responses were determined 1-4 s after CS- termination. Internal consistency was significant for the first (rxy range 0.96-0.90), second (rxy range 0.84-0.54) and third (rxy range 0.96-0.86) skin conductance interval response. Temporal stability was highest for the first interval response (rxy range 0.72-0.37) and lowest for the second interval response (rxy range 0.51-0.05). It is concluded that the first interval skin conductance response shows adequate internal consistency and temporal stability to assess individual differences in classical conditioning.

The high prevalence of diabetes in African-American (AA) women has been widely assumed to be related to the greater prevalence of obesity in this group. Catecholamine release acting on central adipose tissue has been proposed to be a contributing factor. The aim of this article was to examine the interaction of plasma catecholamines and central adiposity on fasting and nonfasting glucose levels in two separate samples. In both studies, the women were healthy, nondiabetic of similar age. In addition, both studies assessed plasma epinephrine (EPI) and norepinephrine (NOREPI) levels collected at three time points. In study 1, catecholamines were measured during a standardized laboratory mental stress task and in study 2, they were measured during the initial phase (10 min) of an intravenous glucose tolerance test (IVGTT). Results from both studies revealed significant effects of EPI on fasting glucose in the obese women. In study 1, mean EPI levels were significantly related to fasting glucose in AA women with high trunk fat (β = 0.60, P < 0.001). Because high BMI was associated with high trunk fat in women, we used BMI >30 as a proxy for high trunk fat (>32%) in study 2. In study 2, EPI response to the glucose bolus was a strong predictor of fasting glucose in AA women with BMI >30 (β = 0.75, P < 0.003). We conclude that the effect of central adiposity on fasting glucose may be moderated by plasma EPI. This suggests that adrenal medullary activity could play a role in the pathophysiology of type 2 diabetes.

According to Eysenck's arousal theory, introverts and individuals high on neuroticism should show greater reactivity and better conditionability than extraverts and individuals low on neuroticism. Forty-six subjects recruited consecutively were subjected to a discriminative Pavlovian conditioning paradigm after being classified in terms of extraversion and neuroticism using a median-split approach. Pictures with a duration of 8 sec served as conditioned stimuli (CS) and a mild electric shock served as an unconditioned stimulus (UCS). Heart rate and multiple electrodermal responses were recorded during a habituation phase (8 trials), an acquisition phase, during which CS+ was paired with UCS— never was (16 trials), and an extinction phase where the electric shocks were withheld (16 trials). During the acquisition phase, introverts displayed greater accelerative unconditioned heart rate responses than extraverts. Introverts conditioned heart rate accelerations to CS+ while extraverts conditioned heart rate decelerations to CS+. There were no significant differences in reactions to CS - between the groups. Extraverts and introverts did not differ in electrodermal reactivity of conditionability. No significant differences were obtained between individuals high and low on neuroticism, neither in cardiovascular nor electrodermal reactivity or conditionability. The present study supports the view that introversion, but not neuroticism, facilities classical conditioning of parasympathetic rather than sympathetic nervous system activity during standard laboratory conditions. This is consistent with the notion that cerebral rather than limbic arousal is associated with conditionability.

To explore the underlying physiology of hostility (HOST) and to test the hypothesis that HOST has a greater impact on fasting glucose in African American (AA) women than it does on AA men or white men or women, using an intravenous glucose tolerance test (IVGTT) and the minimal model of glucose kinetics.A total of 115 healthy subjects selected for high or low scores on the 27 item Cook Medley HOST Scale underwent an IVGTT. Fasting nonesterified fatty acids (NEFA) levels were measured before the IVGTT. Catecholamine levels were measured 10 minutes into the IVGTT.Moderation by group (AA women versus others) of HOST was found for glucose effectiveness (Sg, p = .02), acute insulin response (AIRg, p = .02), and disposition index (DI, p = .02). AA women showed a negative association between HOST and both Sg (beta = -0.45, p = .04) and DI (beta = -0.49, p = .02), controlling for age and body mass index. HOST was also associated with changes in epinephrine (beta = 0.39, p = .05) and fasting NEFA (beta = 0.44, p = .02) in the AA women. Controlling for fasting NEFA reduced the effect of HOST on both Sg and DI.This study shows that HOST is related to decreased DI, a measure of pancreatic compensation for increased insulin resistance as well as decreased Sg, a measure of noninsulin-mediated glucose transport compared in AA women. These effects are partly mediated by the relationship of HOST to fasting NEFA.

Psychosocial stress may play a causative role in development and progression of coronary artery disease (CAD).We investigated the effects of a 1-year stress management program on daily stress behavior and social support among female CAD patients.Women, 247 (or=75 years), hospitalized for a cardiac event were randomized to either a control or an intervention group. Controls obtained usual health care; intervention patients participated in 20 2-h group sessions of stress management therapy and obtained health care by a cardiologist. Measurements were at baseline, 10 weeks (after ten sessions), 1-year (end of intervention), and at a 1- to 2-year follow-up.Daily stress scores for the intervention and control groups were at baseline 39.5 +/- 8.1 vs. 37.2 +/- 9.1 (p = 0.06), 10 weeks 37.2 +/- 8.0 vs. 35.5 +/- 9.4 (p = 0.20), 1-year 36.1 +/- 7.2 vs. 35.9 +/- 8.5 (p = 0.85), and at 1-2 year follow-up 34.0 +/- 7.8 vs. 35.3 +/- 8.7 (p = 0.32), respectively. Intention to treat analyses showed interaction between treatment and time [F(3,213) = 2.72; p = 0.01] reflecting that the decrease was more pronounced in the intervention group. There was no evidence for a difference in change concerning social support.CAD women in the intervention group had a more pronounced reduction of self-rated daily stress behavior over time compared to controls. However, as the intervention group had higher baseline values, due to regression toward the mean, we have no evidence that the difference in decrease of daily stress was due to the intervention.

Background: The isotope-labeled intravenous glucose tolerance test (IVGTT) combined with computer modeling is widely used to derive parameters related to glucose metabolism in vivo. Most of these methods involve use of either 2H2-labeled or 13C1-labeled d-glucose as a tracer with GC-MS to measure the isotope enrichment. These methods are challenging, both technologically and economically. We have developed a novel approach that is suitable for labeled-IVGTT studies involving a large cohort of individuals. Methods: The tracer, d-[13C6]glucose, is a low-cost alternative with the significant advantage that the sixth isotope of natural glucose has virtually zero natural abundance, which facilitates isotopomer analysis with Results: With labeled-IVGTT data from 10 healthy male individuals, the values for insulin sensitivity, glucose effectiveness, and the plasma clearance rate estimated with the 2-pool minimal model compared well with values obtained via traditional methods. Conclusions: The relative simplicity and robustness of the new method permit the preparation and analysis of up to 48 samples/day, a throughput equivalent to 2 complete IVGTT experiments, and this method is readily adaptable to existing 96 well–format purification and analytical systems.

Diabetes patients have a twofold increased risk of suffering from depression as compared to individuals without diabetes. This commonly overlooked comorbidity affects about a quarter of the diabetic population. Because depression among diabetes patients has been associated with decreased metabolic control, poor adherence to medication and diet regimens, a reduction in quality of life, it is of importance for health care providers to recognize and properly treat depression among diabetes patients. When screening for depression, it is important to take into account that the physical symptoms of depression and diabetes overlap to some degree. Also, when deciding on a treatment plan for depression in diabetic patients, the health care provider must be aware of the unique side effects of antidepressants in this population. Psychotherapy and pharmacotherapy are effective in treating depression in the presence of diabetes; both cognitive behavior therapy and selective serotonin reuptake inhibitors have been associated with glycemic improvement in some studies.

Psychosocial factors, including depression and vital exhaustion (VE) are associated with adverse outcome in coronary heart disease (CHD). Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited. This randomized controlled clinical study evaluated the effect of a 1-year stress management program, aimed at reducing symptoms of depression and VE in CHD women.Patients were 247 women,or =75 years, recruited consecutively after a cardiac event and randomly assigned to either stress management (20 2-h sessions) and medical care by a cardiologist, or to obtaining usual health care as controls. Measurements at; baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention sessions), 1 year (end of intervention) and 1-2 years follow-up.For VE, intention to treat analysis showed effects for time (P0.001) and time x treatment interaction (P = 0.005), reflecting that both groups improved over time, and that the decrease of VE was more pronounced in the intervention group. However, the level of VE was higher in the intervention group than amongst controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The change in depressive symptoms did not differ between the groups.CHD women attending our program experienced a more pronounced decrease in VE than controls. However, as they had higher baseline levels, due to regression towards the mean we cannot attribute the decrease in VE to the intervention. Whether the program has long-term beneficial effects needs to be evaluated.

This study examined the associations of depressive symptoms with glucose concentrations and morning cortisol levels in 665 African-American and 4,216 Caucasian Vietnam-era veterans.Glucose level was measured as a three-level variable (diabetes, impaired glucose, and normal). Depressive symptoms were measured by the Obvious Depression Scale (OBD) from the Minnesota Multiphasic Personality Inventory.Regression models showed significant race x OBD interactions in relation to glucose concentration (P0.0001) and cortisol (P0.0001). The OBD was positively associated with glucose concentration and cortisol in both racial groups. However, the magnitude of those associations was larger for African Americans. Further analyses suggested that cortisol partially mediated the race difference in the relation of depressive symptoms to glucose concentrations.These results suggest that enhanced hypothalamic pituitary adrenal activity plays an important role in the relation of depressive symptoms to dysregulated glucose metabolism and may partially explain the differential effects of depressive symptoms on glucose levels in African-American and Caucasian male subjects.

Objective This study aimed to investigate changes in depressive symptoms in hypertensive individuals participating in an exercise and weight loss intervention. Methods This study involved 133 sedentary men and women with high blood pressure (BP; 130–180 mmHg systolic BP and/or 85–110 mmHg diastolic BP) who participated in a 6-month intervention consisting of three groups: aerobic exercise, aerobic exercise and weight loss, and a waiting list control. Results Participants in both treatment groups demonstrated significant improvements in aerobic capacity and lower BP compared with participants in the control group. Participants in the active treatment groups who had mild to moderate depressive symptoms at baseline also exhibited greater reductions in depressive symptoms compared with participants in the control group. Conclusion Results from the present study suggest that exercise, alone or combined with weight management, may reduce self-reported depressive symptoms among patients with hypertension.

ContextObservational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality, but the effects of behavioral interventions on psychosocial and medical end points remain uncertain.ObjectiveTo determine the effect of 2 behavioral programs, aerobic exercise training and stress management training, with routine medical care on psychosocial functioning and markers of cardiovascular risk.Design, Setting, and PatientsRandomized controlled trial of 134 patients (92 male and 42 female; aged 40-84 years) with stable ischemic heart disease (IHD) and exercise-induced myocardial ischemia. Conducted from January 1999 to February 2003.InterventionsRoutine medical care (usual care); usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks; usual care plus weekly 1.5-hour stress management training for 16 weeks.Main Outcome MeasuresSelf-reported measures of general distress (General Health Questionnaire [GHQ]) and depression (Beck Depression Inventory [BDI]); left ventricular ejection fraction (LVEF) and wall motion abnormalities (WMA); flow-mediated dilation; and cardiac autonomic control (heart rate variability during deep breathing and baroreflex sensitivity).ResultsPatients in the exercise and stress management groups had lower mean (SE) BDI scores (exercise: 8.2 [0.6]; stress management: 8.2 [0.6]) vs usual care (10.1 [0.6]; P = .02); reduced distress by GHQ scores (exercise: 56.3 [0.9]; stress management: 56.8 [0.9]) vs usual care (53.6 [0.9]; P = .02); and smaller reductions in LVEF during mental stress testing (exercise: −0.54% [0.44%]; stress management: −0.34% [0.45%]) vs usual care (−1.69% [0.46%]; P = .03). Exercise and stress management were associated with lower mean (SE) WMA rating scores (exercise: 0.20 [0.07]; stress management: 0.10 [0.07]) in a subset of patients with significant stress-induced WMA at baseline vs usual care (0.36 [0.07]; P = .02). Patients in the exercise and stress management groups had greater mean (SE) improvements in flow-mediated dilation (exercise: mean [SD], 5.6% [0.45%]; stress management: 5.2% [0.47%]) vs usual care patients (4.1% [0.48%]; P = .03). In a subgroup, those receiving stress management showed improved mean (SE) baroreflex sensitivity (8.2 [0.8] ms/mm Hg) vs usual care (5.1 [0.9] ms/mm Hg; P = .02) and significant increases in heart rate variability (193.7 [19.6] ms) vs usual care (132.1 [21.5] ms; P = .04).ConclusionFor patients with stable IHD, exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone.

Objective: To test the hypothesis that alcohol consumption is positively related to heart rate variability (HRV) in women with coronary heart disease (CHD) and therefore that cardiac autonomic activity is potentially implicated in the mediation of the favourable effects of moderate drinking. Design, settings, and patients: Cross sectional study of female patients who survived hospitalisation for acute myocardial infarction or underwent a revascularisation procedure, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. Main outcome measures: Ambulatory 24 hour ECG was recorded during normal activities. The mean of the standard deviations of all normal to normal intervals for all five minute segments of the entire recording (SDNNI) and the following frequency domain parameters were assessed: total power, high frequency power, low frequency power, and very low frequency power. A standardised questionnaire evaluated self reported consumption of individual alcoholic beverage types: beer, wine, and spirits. Other clinical characteristics, such as age, body mass index, smoking habits, history of diabetes mellitus, menopausal status, educational status, and treatment, were also assessed. Results: Wine intake was associated with increased HRV in both time and frequency domains independently of other clinical covariates (for example, ln SDNNI was 3.89 among wine drinkers v 3.59 among wine non-drinkers in the multivariate model; p = 0.014). In contrast, consumption of beer and spirits and the total amount of alcohol consumed did not relate significantly to any of the HRV parameters. Conclusion: Intake of wine, but not of spirits or beer, is positively and independently associated with HRV in women with CHD. These results may contribute to the understanding of the complex relation between alcohol consumption and CHD.

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.

Objective To investigate 24-h ambulatory blood pressure measurements (ABPM) as a tool for long-term prediction of future blood pressure (BP) status in high normal and low stage 1 hypertensives. Design, setting and participants A total of 165 men from a population screening program with diastolic BP (DBP) 85-94 mmHg and a systolic BP (SBP) < 150 mmHg performed a 24-h ABPM. Ten years later, 120 participants (73%) returned for renewed measurements. Main outcome measures Blood pressure status at 10 years. Results At the 10-year follow-up, 530/0 of the participants were classified as hypertensive (HT) (BP ≥ 140/90 or taking anti-hypertensive medication) and 47% were classified as normotensive (NT) (BP < 140/90 mmHg). There was no significant baseline differences in office SBP levels between those who were normotensive or hypertensive at follow-up (136/91 versus 138/92 mmHg), whereas both SBP and DBP night-time levels were significantly lower in the future normotensives as compared to the future hypertensives (107/69 versus 112/ 74 mmHg, P < 0.01). Using recommended normalcy night-time ABP levels of < 120/75 mmHg in addition to office BP (140/90) at baseline, over 85% of the subjects were correctly classified provided they met both clinic and ambulatory night-time criteria for HT and NT classification at baseline. Conclusion The use of ABPM in addition to office BP's in patients with borderline hypertension greatly increases the possibility of identifying those individuals who are at a very small risk of developing future hypertension. This could potentially lead to considerable savings in both patient anxiety, physician time and resource consumption.

Despite recent advances in the medical management of hypertension, chronically elevated blood pressure remains a major health problem in the United States, affecting almost 50 million Americans. It is widely recognized that lifestyle factors contribute to the development and maintenance of elevated blood pressure. This article critically reviews current approaches to the nonpharmacological treatment of high blood pressure and highlights outcome studies of exercise, weight loss and dietary modification, and stress management and relaxation therapies. Methodological issues in the assessment and treatment of hypertension are discussed, along with possible mechanisms by which lifestyle modification may reduce elevated blood pressure.

Background Hypertrophy and concentric remodeling of the left ventricle are important manifestations of hypertension that are associated with increased morbidity and mortality. Although lifestyle interventions are efficacious in lowering blood pressure, evidence that they have a beneficial effect on target organs has been lacking. Objective To assess the effects of regular aerobic exercise or exercise plus weight management counseling on left ventricular mass and geometry in overweight, sedentary men and women with high-normal or mildly elevated blood pressure. Methods Eighty-two participants in a randomized, controlled trial were assigned to supervised aerobic exercise only, a behavioral weight management program that included exercise, or a waiting-list control group for 6 months. Blood pressure and echocardiographic measures of left ventricular structure were measured at baseline and at the conclusion of the treatment phase. Results The 45 women and 37 men had a mean ± SD age of 47 ± 9 years and had a mean ± SD blood pressure of 140 ± 10/93 ± 5 mm Hg. Blood pressure fell by 7/6 mm Hg in the weight management group and by 3/4 mm Hg in the aerobic exercise group. In association with these decreases in blood pressure, participants in the intervention groups exhibited significant decreases in left ventricular relative wall thickness ( P = .003), posterior wall thickness ( P = .05), and septal thickness ( P = .004) and a trend toward a decrease in indexed left ventricular mass ( P = .08) relative to the control group. Conclusions In a cohort of overweight, sedentary men and women, exercise and weight loss reduced blood pressure and induced favorable changes in left ventricular structure.

Objective: This study was designed to evaluate the relationship between left ventricular (LV) mass and blood pressure (BP) recorded in the following contexts: in the clinic, using standard auscultatory procedures, during a typical day using ambulatory BP monitoring, and in the laboratory environment during behavioral stress testing. Methods: Ninety-seven men and women with clinic systolic blood pressure (SBP) of 130 to 180 mm Hg and/or diastolic blood pressure (DBP) of 85 to 110 mm Hg and mild to moderate obesity were included in the study. Laboratory stressors included the following tasks: Public Speaking; Anger Interview; Mirror Trace; and Cold Pressor. LV mass was measured using echocardiography and adjusted for body size by dividing by height 2.7 to yield LV mass index (LVMI). Results: LVMI was positively correlated with clinic SBP (r 0.24, p .05), ambulatory SBP (r 0.34, p .01), and aggregated laboratory stress SBP (r 0.28, p .01). Of the individual stressors, only SBP responses to the Mirror Trace and Cold Pressor tasks were independently correlated with LVMI (r 0.35 and 0.34, respectively, p values .01). Hierarchical regression analyses revealed that laboratory stress SBP remained a significant predictor of LVMI, after controlling for BMI and clinic pressure. Conclusions: These findings suggest that cardiovascular responses to behavioral stress are associated with individual differences in LVMI in men and women with high blood pressure who are overweight. Laboratory studies of behavioral stress may help promote our understanding of the pathophysiology of LVH. Key words: left ventricular mass, ambulatory blood pressure, psychological stress, hypertension. SBP systolic blood pressure; DBP diastolic blood pressure; LVMI left ventricular mass index; LVH left ventricular hypertrophy; SVRI systemic vascular resistance index; HR heart rate; CI cardiac index; BMI body mass index. Although hypertension is defined by elevated arterial blood pressure (BP), its clinical significance is primarily due to morbid events affecting the heart and brain. Complications of hypertension, such as myocardial infarction and stroke, are not directly due to elevated pressures, but to the resulting structural changes in the heart and blood vessels. Left ventricular hyper

International audience; While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10−4, N = 12). These results suggest that serotonin is implicated in aspirin response variability.