Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples 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 (0.05/33 = .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 < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

The Effects of Tryptophan Enhancement and Depletion on Plasma Catecholamine Levels in Healthy Individuals.

OBJECTIVE: 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 for 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and 85 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 before and after 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 versus "sham" depletion days. There were also significant day by 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 (Premean = 23.92 (12.23) versus Postmean = 81.57 (62.36)) and decrease in norepinephrine (Premean = 257.2 (106.11) versus Postmean = 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-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS effects in animal models.

Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients.

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.

Effects of exercise and stress management training on nighttime blood pressure dipping in patients with coronary heart disease: A randomized, controlled trial.

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.

Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

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-COX1 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.

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

BACKGROUND: 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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

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.

Changes in body composition predict homocysteine changes and hyperhomocysteinemia in Korea.

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.

Impaired plasmalogens in patients with schizophrenia.

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-naïve 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.

Systolic blood pressure and adiposity: examination by race and gender in a nationally representative sample of young adults.

BACKGROUND: Adiposity, or more specifically, underlying body fat distribution, has been associated with systolic blood pressure (SBP), and it has been suggested that these associations vary between whites and blacks, as well as by gender. METHODS: Here, we use data from the National Longitudinal Study of Adolescent Health (Add Health), a US study of over 15,000 participants (median age 29.0 years), to characterize the associations between measures of body fat distribution-waist circumference (WC) and WC adjusted for body mass index (BMI) (WC(-bmi))-with SBP within white and black race and gender subgroups. RESULTS: Our findings suggest that, at lower levels of WC(-bmi), white women have significantly higher SBP as compared to black women, whereas black men have higher SBP than white men. Black women with WC(-bmi) >90 cm have higher SBP compared to white women with similar WC(-bmi), whereas among black and white men the associations are essentially similar across the full range of WC(-bmi). CONCLUSIONS: The present results suggest that associations among anthropometric measures of adiposity and blood pressure are nonlinear, and importantly, vary for whites and blacks by gender. In black women, SBP increased more as WC increased from low- to mid-range levels, whereas it was only at higher WC levels that black men exhibited higher SBP than white men.

Association of cortisol and the metabolic syndrome in Korean men and women.

Obesity and the metabolic syndrome are closely related and have become increasingly prevalent in Korea. The cardiovascular disease (CVD) risk factors comprising the metabolic syndrome have previously been associated with increased hypothalamic-pituitary-adrenal axis (HPAA) activity, but the associations have not been extensively examined in non-Caucasian populations. The aim of the present study was to investigate the relationships between cortisol, adiposity and the metabolic syndrome in a Korean population. A total of 1,881 adults participated in the study between January 2001 and February 2008. Sociodemographic data were assessed by questionnaires. Body composition, clinic blood pressures as well as metabolic variables including glucose, insulin, and lipid profile were assessed and analyzed in relation to cortisol levels. Mean age of the participants was 58.7 ± 10.8 yr. Higher levels of cortisol was associated with elevated blood pressure, fasting glucose and total cholesterol in men, and between cortisol and systolic blood pressure, fasting glucose and total cholesterol in women. There was an increased risk for the metabolic syndrome associated with higher cortisol levels in both men (P < 0.001) and women (P = 0.040) adjusting for age and body mass index. Higher cortisol levels are associated with several CVD risk factors and the metabolic syndrome, independent of overall of adiposity level, in Korean men and women.

Central nervous system serotonin and clustering of hostility, psychosocial, metabolic, and cardiovascular endophenotypes in men.

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.

Plasma epinephrine predicts fasting glucose in centrally obese African-American women.

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 (beta = 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 (beta = 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.

Hostility and minimal model of glucose kinetics in African American women.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hostility and fasting glucose in African American women.

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.

Daily stress and social support among women with CAD: results from a 1-year randomized controlled stress management intervention study.

BACKGROUND: Psychosocial stress may play a causative role in development and progression of coronary artery disease (CAD). PURPOSE: We investigated the effects of a 1-year stress management program on daily stress behavior and social support among female CAD patients. METHOD: Women, 247 (

Association between n-3 fatty acid consumption and ventricular ectopy after myocardial infarction.

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 + alpha-linolenic acid) was associated with lower ventricular ectopy (beta = -0.35, P = 0.011), and this effect remained after cardiovascular comorbidities were controlled for (beta = -0.47, P = 0.003). Higher concentrations of both marine-based (eicosapentaenoic acid + docosahexaenoic acid) (beta = -0.21, P = 0.060) and plant-based (alpha-linolenic acid) (beta = -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.

A convenient LC-MS method for assessment of glucose kinetics in vivo with D-[13C6]glucose as a tracer.

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 (2)H(2)-labeled or (13)C(1)-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-[(13)C(6)]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 <1% labeled glucose in the infusate. After deproteinization of plasma samples collected at various times, glucose is converted to a stable derivative, purified by solid-phase extraction (SPE), and analyzed by HPLC-electrospray ionization mass spectrometry to accumulate the isotope-abundance data for the A+2, A+3, and A+6 ions of the glucose derivative. A 2-pool modeling program was used to derive standard kinetic parameters. 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.

Financial strain predicts recurrent events among women with coronary artery disease.

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.