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1.
Addict Biol ; : e12855, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789449

RESUMO

DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10-7 , 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P < .05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P < .05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood.

2.
Eur J Epidemiol ; 34(11): 1055-1074, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494793

RESUMO

Inferring a person's smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 ± 0.137, while external model validation in an independent population-based cohort (N = 1608) achieved an AUC of 0.911. These 13 CpGs also provided accurate inference of current (average AUCcrossvalidation 0.925 ± 0.021, AUCexternalvalidation0.914), former (0.766 ± 0.023, 0.699) and never smoking (0.830 ± 0.019, 0.781) status, allowed inferring pack-years in current smokers (10 pack-years 0.800 ± 0.068, 0.796; 15 pack-years 0.767 ± 0.102, 0.752) and inferring smoking cessation time in former smokers (5 years 0.774 ± 0.024, 0.760; 10 years 0.766 ± 0.033, 0.764; 15 years 0.767 ± 0.020, 0.754). Model application to children revealed highly accurate inference of the true non-smoking status (6 years of age: accuracy 0.994, N = 355; 10 years: 0.994, N = 309), suggesting prenatal and passive smoking exposure having no impact on model applications in adults. The finite set of DNA methylation markers allow accurate inference of smoking habit, with comparable accuracy as plasma cotinine use, and smoking history from blood, which we envision becoming useful in epidemiology and public health research, and in medical and forensic applications.

3.
J Psychosom Res ; 123: 109728, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376874

RESUMO

OBJECTIVE: Patients with coronary heart disease (CHD) suffer from physical limitations, but also from psychological distress. Natriuretic peptides may be involved in the neurobiological processes that modulate psychological adaptation, as they are increased in heart disease and seem to have an anxiolytic-like function. Longitudinal data on this association are scarce. METHODS: To assess the relationship between NT-proBNP and anxiety (Hospital Anxiety and Depression Scale (HADS)), we used secondary data from a multicenter trial from baseline to 24 months. Patients (N = 308, 80.8% male, mean age 60.1 years) had stable CHD and moderate levels of depression (HADS ≥8). RESULTS: Multiple linear regression adjusted for age, sex, BMI, and physical functioning revealed NT-proBNP as a significant predictor for anxiety at baseline, 1, 6, 12, 18, and 24 months (all p < .05). Linear mixed model analysis with the six anxiety measures as level-1 variable and NT-proBNP as fixed factor revealed a significant time*NT-proBNP interaction (t(1535.99) = -2.669, p = .01) as well as a significant time*NT-proBNP*sex interaction (t(1535.99) = 3.277, p = .001), when NT-proBNP was dichotomized into lowest vs. the three highest quartiles. CONCLUSION: Our results indicate a stable negative association of baseline NT-proBNP with anxiety over two years. In men and women, different pathways modulating this relationship appear to be in effect. Female patients with very low NT-proBNP levels, despite their cardiac disease, show persistently higher levels of anxiety compared to women with higher levels of NT-proBNP and compared to men. Trial name: A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD). TRIAL REGISTRATION: www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

4.
Public Health Nutr ; : 1-11, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31453792

RESUMO

OBJECTIVE: The origin of malnutrition in older age is multifactorial and risk factors may vary according to health and living situation. The present study aimed to identify setting-specific risk profiles of malnutrition in older adults and to investigate the association of the number of individual risk factors with malnutrition. DESIGN: Data of four cross-sectional studies were harmonized and uniformly analysed. Malnutrition was defined as BMI < 20 kg/m2 and/or weight loss of >3 kg in the previous 3-6 months. Associations between factors of six domains (demographics, health, mental function, physical function, dietary intake-related problems, dietary behaviour), the number of individual risk factors and malnutrition were analysed using logistic regression. SETTING: Community (CD), geriatric day hospital (GDH), home care (HC), nursing home (NH). PARTICIPANTS: CD older adults (n 1073), GDH patients (n 180), HC receivers (n 335) and NH residents (n 197), all ≥65 years. RESULTS: Malnutrition prevalence was lower in CD (11 %) than in the other settings (16-19 %). In the CD sample, poor appetite, difficulties with eating, respiratory and gastrointestinal diseases were associated with malnutrition; in GDH patients, poor appetite and respiratory diseases; in HC receivers, younger age, poor appetite and nausea; and in NH residents, older age and mobility limitations. In all settings the likelihood of malnutrition increased with the number of potential individual risk factors. CONCLUSIONS: The study indicates a varying relevance of certain risk factors of malnutrition in different settings. However, the relationship of the number of individual risk factors with malnutrition in all settings implies comprehensive approaches to identify persons at risk of malnutrition early.

5.
Proc Natl Acad Sci U S A ; 116(23): 11370-11379, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31113877

RESUMO

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-κB-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-κB regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-κB. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-κB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-κB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.

6.
BMC Emerg Med ; 19(1): 31, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046724

RESUMO

BACKGROUND: The substantial increase in cardiovascular diseases (CVD) in China over the last three decades warrants comprehensive preventive primary and secondary strategies. Prolonged prehospital delay (PHD) has been identified as a substantial barrier to timely therapeutic interventions for acute myocardial infarction (AMI). Despite worldwide efforts to decrease the patient's decision-making time, minimal change has been achieved so far. Here, we aim to describe the conceptual framework and methods and outline key data of the MEDEA FAR-EAST Study, which aimed to elucidate in-depth barriers contributing to delay in Chinese AMI-patients. METHODS: Data sources of this multicenter cross-sectional observational study are a standardized bedside interview, a self-administered tailored questionnaire tool and the patient chart. PHD was defined as the main outcome and triangulated at bedside. Standard operation procedures ensured uniform data collection by trained study personnel. The study was ethically approved by Tongji-Hospital and applied to all participating hospitals. RESULTS: Among 379 consecutively screened patients, 296 (78.1%) fulfilled eligibility criteria. A total of 241 (81.4%) AMI-patients were male and 55 (18.6%) female. Mean age was 62.9 years. Prehospital delay time was assessed for 294 (99.3%) patients. Overall median PHD was 151 min with no significant sex difference. Symptom mismatch was present in 200 (69.7%) patients and 106 (39.0%) patients did not attribute their symptoms to cardiac origin. A total of 33 (12.4%) patients suffered from depression, 31 (11.7%) from anxiety and 141 (53.2%) patients employed denial as their major coping style. CONCLUSION: This is the first study on prehospital delay with emphasis on psychological variables in Chinese AMI-patients. A comprehensive assessment tool to measure clinical and psychological factors was successfully implemented. Socio-demographic key data proved a good fit into preexisting Chinese literature. Potential barriers including cardiac denial and symptom-mismatch were assessed for the first time in Chinese AMI-patients. The pretested selection of instruments allows future in depth investigations into barriers to delay of Chinese AMI-patients and enables inter-cultural comparisons.

7.
Eur J Prev Cardiol ; : 2047487319839183, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31030552

RESUMO

BACKGROUND: Although work stress and impaired sleep are established risk factors for cardiovascular disease (CVD) among healthy individuals, their impact on hypertensive workers is largely unknown. DESIGN: Prospective cohort study design. METHODS: Hypertensive workers ( N = 1959), derived from the population-based MONICA/KORA study in Southern Germany, who were free of any cardiovascular disease and diabetes were interviewed at baseline for work stress (high demand plus low control) and impaired sleep (difficulties falling asleep and/or maintaining sleep). Hazard ratios and 95% confidence intervals (CIs) were estimated by multivariate Cox proportional hazards models with adjustment for relevant covariates. RESULTS: During a mean follow-up of 17.8 years covering 34,900 person-years, 134 fatal CVD and 73 coronary heart disease (CHD) events were observed. In comparison to participants with low work stress and non-impaired sleep, participants with work stress (hazard ratio (HR) 1.56, 95% CI 0.81-2.98), or impaired sleep (HR 1.76, 95% CI 0.96-3.22) had an increased risk of CVD, while participants with both work stress and impaired sleep had the highest risk of CVD mortality (HR 2.94, 95% CI 1.18-7.33). Participants with both risk conditions had an absolute CVD mortality risk of 7.13 cases per 1000 person-years in comparison to 3.05 cases per 1000-person years in the reference group. Similar risk patterns were found for CHD mortality. CONCLUSIONS: Our findings add a new piece of evidence that work stress together with impaired sleep increase risk of coronary and cardiovascular mortality in hypertensive workers.

8.
Int Arch Allergy Immunol ; 179(4): 262-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31018198

RESUMO

BACKGROUND: Psychosocial factors are supposed to play a central role in the development of allergic diseases. Associations with seasonal and perennial forms of allergies have not been investigated, yet. OBJECTIVES: The aim of the study was to investigate the associations of psychosocial factors (social status, depression, generalized anxiety, psychosocial stress, Type-D personality) with seasonal, perennial, and other forms of allergies in adults. METHOD: The analysis of self-reported data of the KORA FF4 study was performed with SAS 9.4. The sample consisted of 1,782 study participants in the study region of Augsburg (39-88 years, 61 years, 51.1% female). Descriptive bivariate statistics and multinomial logistic regression models were performed. Age, sex, family predisposition, and smoking status were considered possible confounders. Moreover, several sensitivity analyses were carried out to check whether missing values distorted the results. RESULTS: A positive association between generalized anxiety and seasonal allergies was found in the multivariate model. Depression was positively, and anxiety negatively, associated with perennial allergies. No association between the analyzed psychosocial factors and other forms of allergies could be found. CONCLUSION: The results support the relevance of psychosocial factors in association with allergies. Looking at the psychosocial factors, a separate consideration of seasonal and perennial allergies seems reasonable. Further longitudinal studies should investigate the direction of the associations, the underlying mechanisms, and other psychosocial factors, such as coping mechanisms, in confirmed allergies.


Assuntos
Ansiedade , Depressão , Rinite Alérgica Perene/psicologia , Rinite Alérgica Sazonal/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Psicologia , Rinite Alérgica Perene/epidemiologia , Rinite Alérgica Sazonal/epidemiologia , Autorrelato , Fatores Socioeconômicos , Estresse Psicológico
9.
Eur J Epidemiol ; 34(7): 675-687, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30941552

RESUMO

Morbidity trends may result from cohort experiences in critical developmental age. Our objective was to compare the health status of 65-71 year-olds who were in critical developmental age before (1937-June 1945), during (June 1945-June 1948) and after (June 1948-1950) the early reconstruction and food crisis (ERFC) period in Germany following World War II. Data originate from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study in Southern Germany. We used the 2008 baseline sample born 1937-1943 and the 2015 enrichment sample born 1944-1950. Health status was assessed as the number of accumulated health deficits using a Frailty Index (FI). Cohorts were defined based on co-occurrence of critical developmental age (gestation and the first 2 years of life) and the ERFC period. Cohort, age and sex effects on older-age health status were analyzed using generalized linear models. We included 590 (53% male) pre-war and war (PWW), 475 (51% male) ERFC and 171 post-currency reform (PCR) cohort participants (46% male). Adjusted for covariates, FI levels were significantly higher for the ERFC (Ratio 1.14, CL [1.06, 1.23]) but not for the PCR (Ratio 1.06, CL [0.94, 1.20]) as compared to the PWW cohort. Being in critical developmental age during the ERFC period increased FI levels in adults aged 65-71 years. Covariates did not explain these effects, suggesting a direct detrimental effect from being in critical developmental age during the ERFC period on older-age health. This expansion of morbidity in Germany was not detected in the PCR cohort.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Nível de Saúde , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Morbidade/tendências , Fatores Sexuais , Fatores Socioeconômicos , II Guerra Mundial
10.
BMC Psychiatry ; 19(1): 57, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717711

RESUMO

BACKGROUND: Depressive symptoms are common in patients with coronary artery disease (CAD) and are associated with an unfavourable outcome. Establishing prognostic patient profiles prior to the beginning of mental health care may facilitate higher efficacy of targeted interventions. The aim of the current study was to identify sociodemographic and somatic predictors of depression outcome among depressed patients with CAD. METHODS: Based on the dataset of the multicentre SPIRR-CAD randomised controlled trial (n = 570 patients with CAD and ≥ 8 points on the Hospital Anxiety and Depression Scale (HADS)), 141 potential sociodemographic and somatic predictors of the change in the HADS-D depression score from baseline to 18-month-follow-up were derived in two different ways. We screened for univariable association with response, using either analysis of (co)variance or logistic regression, respectively, both adjusted for baseline HADS-D value and treatment group. To guard against overfitting, multivariable association was evaluated by a linear or binomial (generalised) linear model with lasso regularisation, a machine learning approach. Outcome measures were the change in continuous HADS-D depression scores, as well as three established binary criteria. The Charlson Comorbidity Index (CCI) was calculated to assess possible influences of comorbidities on our results and was also entered in our machine learning approach. RESULTS: Higher age (p = 0.002), unknown previous myocardial infarction (p = 0.013), and a higher heart rate variability during numeracy tests (p = .020) were univariably associated with a favourable depression outcome, whereas hyperuricemia (p ≤ 0.003), higher triglycerides (p = 0.014), NYHA class III (p ≤ 0.028), state after resuscitation (p ≤ 0.042), intake of thyroid hormones (p = 0.007), antidiabetic drugs (p = 0.015), analgesic drugs (p = 0.027), beta blockers (p = 0.035), uric acid drugs (p ≤ 0.039), and anticholinergic drugs (p = 0.045) were associated with an adverse effect on the HADS-D depression score. In all analyses, no significant differences between study arms could be found and physical comorbidities also had no significant influence on our results. CONCLUSION: Our findings may contribute to identification of somatic and sociodemographic predictors of depression outcome in patients with CAD. The unexpected effects of specific medication require further clarification and further research is needed to establish a causal association between depression outcome and our predictors. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00705965 (registered 27th of June, 2008). www.isrctn.com ISRCTN76240576 (registered 27th of March, 2008).


Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/psicologia , Depressão/diagnóstico , Depressão/psicologia , Sintomas Inexplicáveis , Apoio Social , Idoso , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Intervenção Coronária Percutânea , Fatores Socioeconômicos , Resultado do Tratamento
13.
Eur Heart J ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30462213

RESUMO

Aims: To investigate the clinical value of a lower blood pressure (BP) cut-off for Stage 1 (S1) hypertension (130-139 mmHg systolic or 80-89 mmHg diastolic) in comparison to the currently established Stage 2 (S2) cut-off (≥140/90 mmHg) in a population-based cohort. Methods and results: We assessed the hypertension prevalence and associated cardiovascular disease (CVD) events in a sample of 11 603 participants (52% men, 48% women; mean 47.6 years) from the MONICA/KORA prospective study. The implementation of the new S1 cut-off increased the prevalence of hypertension from 34% to 63%. Only 24% of S2 hypertension patients were under treatment. Within a follow-up period of 10 years (70 148 person-years), 370 fatal CVD events were observed. The adjusted CVD-specific mortality rate per 1000 persons was 1.61 [95% confidence interval (CI) 1.10-2.25] cases in S2 and 1.07 (95% CI 0.71-1.64) cases in S1 hypertension in comparison to normal BP. Cox proportional regression models were significant for the association of S2 and CVD mortality (1.54, 95% CI 1.04-2.28, P = 0.03), also in the presence of competing risks (1.47, P = 0.05). However, statistical significance for S1 hypertension was not reached (0.93, 95% CI 0.61-1.44, P = 0.76). Among S2 participants, there was a significantly higher prevalence of depressed-mood in treated patients (47%) in comparison to non-treated patients (33%) (P < 0.0001). Conclusion: The lower BP cut-off substantially increased hypertension prevalence, while capturing a population with lower CVD mortality. Additionally, participants under treatment were more likely to have depressed-mood in comparison to non-treated participants, which might reflect a negative labelling effect.

14.
J Psychosom Res ; 113: 89-99, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30190055

RESUMO

INTRODUCTION: The biological and psychosocial risk profile differs between women and men with coronary artery disease (CAD). Depressive symptoms and Vital Exhaustion (VE) predict an unfavourable course of CAD. The secondary analysis of the SPIRR-CAD trial offered the possibility to examine gender as exposure variable of the clinical and psychological situation at baseline and in a variety of psychosocial measures as outcomes. METHODS: In this trial, 450 men (78.9%) and 120 women (21.1%) with CAD (age ≤ 75 y), with mild to moderate depression (scoring ≥8 on the HADS), were randomized to usual care with or without a stepwise psychotherapy intervention. Beside clinical measures exhaustion and other indicators of depressive symptoms were collected at baseline and 18-month follow up. RESULTS: Men had more signs and symptoms of heart disease at baseline, whereas women had higher psychosocial burden (e.g. negative affect). Women were more likely to live alone, had lower educational levels and employment rates and higher levels of depression and exhaustion. The psychotherapy intervention differed as a function of gender: In women, VE decreased from 29.4 ±â€¯8.1 to 22.1 ±â€¯11.7 in the intervention group (IG) and from 29.2 ±â€¯8.2 to 25.1 ±â€¯11.3 in the control group (CG). In men VE decreased from 23.3 + -10.8 to 21.2 ±â€¯9.7 in the IG and from 23.6 ±â€¯10.7 to 19.3 ±â€¯11.3 in the CG (time x intervention x gender; F = 4.97; p = .026). DISCUSSION: Women had a higher psychosocial burden than men. VE compared to other rating instruments of depressive symptoms suggested a stronger response to the intervention in women. VE may help to understand gender differences in psychotherapeutic treatment studies of CAD. ISRCTN: 76240576; clinicaltrials.gov.

15.
J Am Geriatr Soc ; 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30136728

RESUMO

OBJECTIVES: To identify determinants of incident malnutrition in community-dwelling older adults. DESIGN: Meta-analysis of 6 community-based longitudinal datasets with follow-up of 1 to 3 years. SETTING: Datasets from MaNuEL (MalNutrition in the Elderly) partners were included: 3 studies from Germany and 1 each from Ireland, the Netherlands, and New Zealand. PARTICIPANTS: community-dwelling adults aged 65 and older (N=4,844). MEASUREMENT: The same definition of incident malnutrition was used for all cohorts (body mass index < 20.0 kg/m2 at follow-up or weight loss ≥10 % between baseline and follow-up). Twenty-one potential baseline determinants from 7 domains (demographic, nutritional, lifestyle, social, psychological, physical functioning, medical) and 2 follow-up variables (hospitalization, falls) were harmonized for all studies. Binary logistic regression analyses were performed to assess the association between each variable, adjusted for specific confounders, and incident malnutrition. Combined odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects meta-analyses. RESULTS: Studies included between 209 and 1,841 participants without malnutrition at baseline; mean age ranged from 71.7 to 84.6. Incidence of malnutrition varied from 5.1% and 17.2%. Meta-analyses identified 6 variables as independent determinants of incident malnutrition; with increasing age, the risk of developing malnutrition increased continuously. Unmarried, separated, or divorced participants were more likely to develop malnutrition than married participants, whereas no association was found for widowed participants. Participants with difficulty walking (OR=1.41, 95% CI=1.06-1.89) or difficulty climbing stairs (OR=1.45, 95% CI=1.14-1.85) and those who were hospitalized before baseline (OR=1.49, 95% CI=1.25-1.76) and during follow-up (OR=2.02, 95% CI=1.41-2.88) had higher odds of incident malnutrition. CONCLUSION: In this harmonized meta-analysis based on prospective data of older, community-dwelling adults, age, marital status, limitations with walking and climbing stairs, and hospitalization were identified as determinants of incident malnutrition.

16.
Psychoneuroendocrinology ; 96: 188-194, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29982099

RESUMO

Natriuretic peptides (NP) are involved in the regulation of blood pressure and blood volume, and are elevated in patients with coronary artery disease (CAD). They are used as markers for illness severity, but their role in mental health is not well understood. Recently, A-type NP (ANP) has been associated with reduced anxiety in studies on cardiac patients; however, this study is the first to assess this effect for B-type NP (BNP) and for further dimensions of well-being and mental health. Depression, anxiety, and distress are more common in CAD patients than in the general population and are most likely not only influenced by psychological adaptation but also by neurobiological processes. We used baseline N-terminal proBNP (NT-proBNP) samples and psychometric assessments of 529 at least mildly depressed (Hospital Anxiety and Depression Scale, depression score ≥ 8) CAD patients from the multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial. Psychosocial status was assessed using standardized self-rating questionnaires on anxiety, depression, coping with illness, vital exhaustion, type D personality, and quality of life. Separate linear regression models for each psychometric scale revealed significant negative correlations of NT-proBNP with anxiety, depression, vital exhaustion, depressive coping, and negative affectivity. Moreover, patients with higher levels of NT-proBNP experienced less bodily pain and had a better self-rated mental health, despite worse physical functioning. Linear regression adjusted for age, sex, and physical functioning (Short Form Health Survey [SF-36]) revealed NT-proBNP to be a significant predictor for all tested measures of the patients' psychosocial status. These results indicate that NT-proBNP is not only positively associated with greater disease severity in mildly to moderately depressed CAD patients but also with better psychosocial status and mental well-being. Possible mechanisms of this effect are discussed.

17.
JAMA Psychiatry ; 75(9): 949-959, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29998287

RESUMO

Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers. Objective: To identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood. Design, Setting, and Participants: To date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts. Main Outcomes and Measures: Whole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire. Results: The discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%] women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 × 10-08; n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 × 10-09; n = 11 256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 × 10-08; n = 11 256; chromosome = 15q26.1). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 × 10-03) and of ARHGEF3 in fibroblasts (effect, -0.48; P = 9.8 × 10-04) was associated with major depression. Conclusions and Relevance: This study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects.

18.
BMC Public Health ; 18(1): 754, 2018 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-29914437

RESUMO

BACKGROUND: Job insecurity has been associated with impaired self-rated health (SRH) in cross-sectional studies, but prospective findings with short, medium and long-term follow-up yielded mixed findings. Therefore, the aim of the present study was to assess the long-term association between perceived job insecurity and SRH, after controlling for baseline levels of health status and life-style choices. Furthermore, three different follow-up periods (14, 19 and 24 years) were considered. METHODS: Data were derived from the prospective population-based MONICA/KORA cohort study (southern Germany). N = 4356 participants (2622 men and 1734 women), aged between 25 and 64 years at baseline, were included in the sample, mean follow-up was after 19.1 years. Job insecurity, SRH and risk factors were assessed at baseline during three independent surveys (1984-1995). SRH was additionally assessed in 2009. The association of job insecurity and impaired SRH at follow-up was estimated using logistic regression analyses. RESULTS: Overall, perceiving job insecurity at baseline was significantly associated with a 20% higher risk of developing impaired SRH at follow-up in the pooled analysis (OR = 1.20, 95% CI = 1.01-1.43, p = .034), even after controlling for baseline SRH, socio-demographic characteristics, lifestyle, clinical and work-related factors. The association was strongest and significant after 14 years (OR = 1.58, 95% CI 1.17-2.13, p = .003) and weaker and not significant to 19 (OR = 1.20, 95% CI 0.89-1.62, p = .24) and 24 years (OR = 0.98, 95% CI 0.73-1.32, p = .89) of follow-up in the fully adjusted models. CONCLUSIONS: We found that perceived job insecurity during working life was independently and significantly associated with impaired SRH both cross-sectionally as well as after 14 years, but not after 19 and 24 years.

19.
J Psychosom Res ; 108: 39-46, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29602324

RESUMO

OBJECTIVE: The relationship between attachment orientations and the recovery from depressive symptoms in patients diagnosed with coronary artery disease (CAD) with and without a psychotherapeutic intervention was examined in this study. METHODS: In a multicenter trial of 570 depressed CAD patients (SPIRR-CAD), assigned to usual care plus either a stepwise psychotherapy intervention or one information session, 522 patients provided attachment data at baseline. Attachment was measured with the Relationship Scales Questionnaire (RSQ), yielding four attachment orientations. The primary outcome was change in Hospital Anxiety and Depression Scale depression (HADS-D) scores from baseline to follow-up at 18 months. Secondary outcomes were HADS-D scores at 1, 6, 12, and 24 months. RESULTS: Independent of treatment assignment, attachment was related to change in depression at 18 months (p < 0.01) with secure attachment resulting in a significant reduction (-2.72, SE = 0.27) in depression compared to dismissive-avoidant (-1.51, SE = 0.35, p = 0.040) and fearful-avoidant (-0.65, SE = 0.61, p = 0.012) attachment. Patients with anxious-preoccupied attachment showed changes similar to secure attachment (-2.01, SE = 0.47). An explorative subgroup analysis across all assessment time points revealed patients with a dismissive-avoidant attachment benefitted from psychotherapy (average mean difference = 0.93, SE = 0.47, p = 0.048). CONCLUSION: Attachment played an important role for improvement in depressive symptoms. Only dismissive-avoidant patients seemed to benefit from the intervention. The lack of improvement in fearful-avoidant patients shows a need for specific interventions for this group. TRIAL REGISTRATION: www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

20.
Int Arch Occup Environ Health ; 91(5): 623-631, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29687327

RESUMO

OBJECTIVES: Emerging cross-sectional research has identified lack of supportive leadership behavior (SLB) as a risk factor for workforce health. However, prospective evidence is hitherto lacking. SLB denotes support in difficult situations, recognition and feedback on work tasks. This study aims to determine the effect of SLB on suboptimal self-rated health (SRH) after 10 years considering potential moderators such as ages, sex, occupation and job strain. METHODS: The sample included 884 employed participants drawn from the population-based prospective MONICA/KORA Study. SLB, SRH, as well as job strain were assessed by questionnaire. Logistic regressions estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the effect of SLB at baseline on suboptimal SRH at follow-up. Analyses were adjusted for age, gender, lifestyle (alcohol, smoking, physical activity), socioeconomic status as well as for SRH and job strain at baseline. RESULTS: Lack of SLB was associated with suboptimal SRH at baseline [OR 2.00, (95% CI 1.19-3.46)] and at follow-up [OR 2.33, (95% CI 1.40-3.89)]. Additional adjustment for job strain did not substantially alter this association [OR 2.06, (95% CI 1.20-3.52)]. However, interactions between SLB and job strain as well as gender became evident, indicating moderating influences on the association between SLB and SRH. CONCLUSION: Lack of supportive leadership was associated with suboptimal SRH at 10 years' follow-up in men, even if SRH at baseline and other risk factors were taken into account. This effect is likely to be moderated by job strain.


Assuntos
Nível de Saúde , Liderança , Estresse Ocupacional/psicologia , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Relações Interprofissionais , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Apoio Social , Inquéritos e Questionários
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