Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus-results from the randomized, double-blind, placebo-controlled EmDia trial.

BACKGROUND: The sodium-glucose co-transporter 2 inhibitor empagliflozin improves cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM) and heart failure. Experimental studies suggest a direct cardiac effect of empagliflozin associated with an improvement in left ventricular diastolic function. METHODS: In the randomized, double-blind, two-armed, placebo-controlled, parallel group trial EmDia, patients with T2DM and elevated left ventricular E/E´ ratio were enrolled and randomized 1:1 to receive empagliflozin 10 mg/day versus placebo. The primary endpoint was the change of left ventricular E/E´ ratio after 12 weeks of intervention. RESULTS: A total of 144 patients with T2DM and an elevated left ventricular E/e´ ratio (age 68.9 ± 7.7 years; 14.1% women; E/e´ ratio 9.61[8.24/11.14], left ventricular ejection fraction 58.9% ± 5.6%). After 12 weeks of intervention, empagliflozin resulted in a significant higher decrease in the primary endpoint E/e´ ratio by - 1.18 ([95% confidence interval (CI) - 1.72/- 0.65]; P < 0.0001) compared with placebo. The beneficial effect of empagliflozin was consistent across all subgroups and also occurred in subjects with heart failure and preserved ejection fraction (n = 30). Additional effects of empagliflozin on body weight, HbA1c, uric acid, red blood cell count, hemoglobin, mean corpuscular hemoglobin, and hematocrit were detected (all P < 0.001). Approximately one-third of the reduction in E/e´ by empagliflozin could be explained by the variables examined. CONCLUSIONS: Empagliflozin improves diastolic function in patients with T2DM and elevated end-diastolic pressure. Since the positive effects were consistent in patients with and without heart failure with preserved ejection fraction, the data add a mechanistic insight for the beneficial cardiovascular effect of empagliflozin. TRIAL REGISTRATION: Clinicaltrials.gov, unique identifier: NCT02932436.

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

AIMS: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome. METHODS AND RESULTS: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality. CONCLUSION: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.

Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study.

BACKGROUND: Data of the EMPA-REG OUTCOME study have demonstrated a beneficial effect of the sodium-glucose cotransporter 2 inhibitor empagliflozin on cardiovascular outcome in patients with type 2 diabetes. The reduction in cardiovascular mortality and hospitalization due to heart failure might be in part explained by the direct effects of empagliflozin on cardiac diastolic function. The EmDia trial investigates the short-term effects of empagliflozin compared to placebo on the left ventricular E/E' ratio as a surrogate of left ventricular diastolic function. METHODS: EmDia is a single-center, randomized, double-blind, two-arm, placebo-controlled, parallel group study of phase IV. Individuals with diabetes mellitus type 2 (T2DM) are randomized 1:1 to receive empagliflozin 10 mg per day or a placebo for 12 weeks. The main inclusion criteria are diagnosed as T2DM with stable glucose-lowering and/or dietary treatment, elevated HbA1c level (6.5-10.0% if receiving glucose-lowering therapy, or 6.5-9.0% if drug-naïve), and diastolic cardiac dysfunction with left ventricular E/E'≥8. The primary end point is the difference of the change in the E/E' ratio by treatment groups after 12 weeks. Secondary end points include assessment of the effect of empagliflozin on left ventricular systolic function, measures of vascular structure and function, as well as humoral cardiovascular biomarkers (i.e. brain natriuretic peptide, troponin, C-reactive protein). In addition, the multidimensional biodatabase enables explorative analyses of molecular biomarkers to gain insights into possible mechanisms of the effects of empagliflozin on human health in a systems medicine-oriented, multiomics approach. CONCLUSION: By evaluating the short-term effect of empagliflozin with a comprehensive biobanking program, the EmDia Study offers an opportunity to primarily assess the effects on diastolic function but also to examine effects on clinical and molecular cardiovascular traits. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02932436. Registration date, 2016/10/13.

Right atrium size in the general population.

Echocardiography is the most common routine cardiac imaging method. Nevertheless, only few data about sex-specific reference limits for right atrium (RA) dimensions are available. Transthoracic echocardiographic RA measurements were studied in 9511 participants of the Gutenberg-Health-Study. A reference sample of 1942 cardiovascular healthy subjects without chronic obstructive pulmonary disease was defined. We assessed RA dimensions and sex-specific reference limits were defined using the 95th percentile of the reference sample. Results showed sex-specific differences with larger RA dimensions in men that were attenuated by standardization for body-height. RA-volume was 20.2 ml/m in women (5th-95th: 12.7-30.4 ml/m) and 26.1 ml/m in men (5th-95th: 16.0-40.5 ml/m). Multivariable regressions identified body-mass-index (BMI), coronary artery disease (CAD), chronic heart failure (CHF) and atrial fibrillation (AF) as independent key correlates of RA-volume in both sexes. All-cause mortality after median follow-up-period of 10.7 (9.81/11.6) years was higher in individuals who had RA volume/height outside the 95% reference limit (HR 1.70 [95%CI 1.29-2.23], P = 0.00014)). Based on a large community-based sample, we present sex-specific reference-values for RA dimensions normalized for height. RA-volume varies with BMI, CHF, CAD and AF in both sexes. Individuals with RA-volume outside the reference limit had a 1.7-fold higher mortality than those within reference limits.

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study.

AIMS: Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. METHODS AND RESULTS: Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40-80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6-37.4%], 13.3% [12.6-13.9%], and 40.8% [39.9-41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19-1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11-2.05), P = 0.009]. CONCLUSION: Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.

What's past is prologue: Recalled parenting styles are associated with childhood cancer survivors' mental health outcomes more than 25 years after diagnosis.

BACKGROUND: With the increased survival rates of childhood cancer, long-term survivors' well-being over the life span has come into focus. A better understanding of the determinants of childhood cancer survivors' (CCS) mental health outcomes contributes to the identification of vulnerable individuals as well as to the development of evidence-based prevention and intervention efforts. It has been noted that psychosocial factors such as parental rearing behavior shape individual differences in mental health. There is also evidence that parents show altered parenting behavior in the face of childhood cancer, e. g. that they express more emotional support, but also more worries. However, little is known about the relevance of different parenting styles for CCS' mental health decades after diagnosis and treatment. METHODS: We examined the associations of recalled parenting styles and disease-related factors with lifetime diagnoses of depression and anxiety disorders in a German, registry-based sample of adult CCS (N = 948, 44.50% women) with survival times >25 years. We conducted logistic regression analyses of lifetime diagnoses of depression and anxiety disorders, respectively, on dimensions of recalled parental rearing behavior (measured with a validated German short version of the EMBU) controlling for relevant adjustment variables such as the presence of physical illnesses. RESULTS: Recalled parenting styles of both parents had statistically relevant associations with CCS' lifetime depression and anxiety diagnoses. Maternal emotional warmth was related to fewer lifetime diagnoses of depression and fewer lifetime diagnoses of anxiety. Memories of paternal control and overprotection were positively associated with lifetime diagnoses of anxiety. CONCLUSION: The results indicate that mental representations of one's caregivers are associated with psychological long-term outcomes. Thus, medical professionals should involve the parents and support them in accompanying their child through the difficult times of treatment and survivorship. Interventions aimed at fostering survivors' quality of life should consider the sustained relevance of early relationships.

Risk factors for suicidal ideation in a large, registry-based sample of adult long-term childhood cancer survivors.

INTRODUCTION: Long-term childhood cancer survivors (CCS) are at risk for physical and psychosocial late effects. Previous research has attested to increased rates of suicidal ideation (SI) in CCS, an especially dangerous indicator of distress. However, little was known about risk factors of SI among CCS which go beyond illness- and treatment related variables. METHODS: A registry-based sample of 916 adult long-term CCS (Mage=34.58 years [SD=5.53], Mage at diagnosis=6.15 years [SD=4.28]) underwent medical assessments and filled out questionnaires. We conducted a linear regression analysis on SI, testing predictors of different areas: sociodemographic, social, physical health and health behavior, and psychological distress symptoms. RESULTS: SI was reported by 73 (8.0%) CCS and previous suicide attempts were reported by 26 (2.8%) CCS. SI was most closely related to social and psychological factors, i.e. to concurrent distress symptoms (depression, anxiety, social phobia), previous suicide attempts, current loneliness, and the present living situation. LIMITATIONS: SI and previous suicide attempts were assessed using short self-report instruments. The cross-sectional study design does not allow for causal inferences. CONCLUSIONS: Long-term CCS are a previously understudied, vulnerable group. Decades after having survived cancer, a considerable percentage is affected by (recurrent) SI. CCS' risk for SI is likely shaped by individual medical and psychological history, and by the current social environment and psychological comorbidities. There is a need for more interdisciplinary research and for screening efforts which take account of these factors. Interventions reducing CCS' risk of suicide should foster social integration and counteract current stressors.

Status and predictors of planning ability in adult long-term survivors of CNS tumors and other types of childhood cancer.

Long-term childhood cancer survivors' (CCS) quality of life can be impacted by late effects such as cognitive difficulties. Especially survivors of CNS tumors are assumed to be at risk, but reports of cognitive tests in CCS with survival times >25 years are scarce. We assessed planning ability, a capacity closely related to fluid intelligence, using the Tower of London. We compared 122 CNS tumor survivors, 829 survivors of other cancers (drawn from a register-based sample of adult long-term CCS), and 215 healthy controls (using sex-specific one-way ANOVAs and t-tests). Associations of CCS' planning ability with medical and psychosocial factors were investigated with a hierarchical linear regression analysis. Mean planning ability did not differ between CCS and controls. However, female CNS tumor survivors performed worse than female survivors of other cancers and female controls. CNS tumor survivors of both sexes had a lower socioeconomic status, and fewer of them had achieved high education than other survivors. In the regression analysis, lower status and anxiety symptoms were associated with poor planning, suggesting possible mediators of effects of disease and treatment. The results indicate the necessity to contextualize test results, and to include cognitive and psychological assessments into aftercare.

Parenting in the face of serious illness: Childhood cancer survivors remember different rearing behavior than the general population.

OBJECTIVE: A child's cancer diagnosis and treatment affect the whole family. While it has been recognized that parents are an important resource for their children, little is known about the specifics of parenting in the face of serious illness. METHODS: We used the Recalled Parental Rearing Behavior Questionnaire in a register-based cohort of adult childhood cancer survivors (CCS) (N = 951) and a representative population sample of the same age range (N = 2042). The questionnaire assesses behavior of mothers and fathers with three scales (emotional warmth, rejection/punishment, and control/overprotection) by querying the (former) child. We compared the two groups using general linear models. With a hierarchical linear regression analysis, we tested associations of recalled rearing behavior with disease- and treatment-related factors. RESULTS: Compared with the general population, CCS remembered both parents as emotionally warmer, more overprotective, and less punishing/rejecting and less ambitious. The regression analysis showed that having received radiotherapy (ß = 0.092; P = .009) and chemotherapy (ß = 0.077; P = .027) was positively related to memories of maternal emotional warmth. CONCLUSIONS: CCS remembered parenting styles which are generally deemed more positive. The extent of recalled control and overprotection deviated from the population in different directions, suggesting that parenting in childhood cancer entails more complex adaptations than being affectionate and giving comfort. The results suggest an adaptation of parental behavior to particularly challenging treatments. They highlight potential vulnerability and resilience factors, some of which were sex-dependent.

Income and education predict elevated depressive symptoms in the general population: results from the Gutenberg health study.

BACKGROUND: Socioeconomic status (SES) has a strong association with depression or physical and mental health in general. However, as SES is a multifaceted construct these associations are not easy to explain. Further, there are several indicators and many studies only investigating two or less indicators at the same time. Therefore, this study aims to analyze the cross-sectional and longitudinal association of three defined SES dimensions (education, occupational position and household net-income) with the occurrence of elevated symptoms of depression relative to the impact of important covariates. METHODS: The study included observational data from 12,484 participants of the Gutenberg Health Study. The outcome was "elevated depressive symptoms" as defined by Patient Health Questionnaire (PHQ-2) ≥ 2 at the 2.5-year follow-up. Regression coefficients were adjusted for baseline covariates (age, sex, partnership, depression, anxiety, medical history of depressive or anxiety disorder and major medical diseases (MMD)) in addition to SES sum score and the three single indicators. We further examined interaction terms of the SES with sex, partnership and major medical diseases. We analyzed the sample stratified by elevated depressive symptoms at baseline, as we expected different trajectories in both subgroups. RESULTS: SES, education and household net-income were lower in the group of persons with PHQ-2 ≥ 2 at baseline, and they predicted the occurrence of PHQ-2 ≥ 2 at 2.5 year follow-up in the group of persons without elevated depressive symptoms at baseline after multivariable adjustment (SES: Odds Ratio (OR) 0.96, 0.95-0.98, p <  0.0001; education: OR 0.96, 0.93-0.99, p = 0.036; household net-income: OR 0.96, 0.92-0.99, p = 0.046) but not in the group of persons with elevated depressive symptoms at baseline. Further, we found that the impact of major medical diseases on the development of elevated depressive symptoms was buffered by high income. In addition, living in a partnership buffered the impact of a low occupational position. CONCLUSIONS: Regarding the SES, the dimensions education and household net-income seem to play the most important role for socioeconomic inequalities in persons in Mid-West Germany with depressive symptoms. TRIAL REGISTRATION: Reference no. 837.020.07; original vote: 22.3.2007, latest update: 20.10.2015.

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population-Based Gutenberg Health Study.

Background Preclinical data have indicated a link between use of vitamin K antagonists ( VKA ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population. Methods and Results Clinical and laboratory data, as well as medical-technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5-hour visit at the study center of the population-based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an independent association between VKA intake and stiffness index (ß=+2.54 m/s; [0.41/4.66]; P=0.019), ankle-brachial index (ß=-0.03; [-0.04/-0.01]; P<0.0001), intima-media thickness (ß=+0.03 mm [0.01/0.05]; P=0.0098), left ventricular ejection fraction (ß=-4.02% [-4.70/-3.33]; P<0.0001), E/E' (ß=+0.04 [0.01/0.08]; P=0.014) left ventricular mass (ß=+5.34 g/m2.7 [4.26/6.44]; P<0.0001), and humoral markers of cardiac function and inflammation (midregional pro-atrial natriuretic peptide: ß=+0.58 pmol/L [0.50/0.65]; P<0.0001; midregional pro-adrenomedullin: ß=+0.18 nmol/L [0.14/0.22]; P<0.0001; N-terminal pro B-type natriuretic peptide: ß=+1.90 pg/mL [1.63/2.17]; P<0.0001; fibrinogen: ß=+143 mg/dL [132/153]; P<0.0001; C-reactive protein: ß=+0.31 mg/L [0.20/0.43]; P<0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of VKA demonstrated consistent and robust results. Genetic variants in CYP 2C9, CYP 4F2, and VKORC 1 were modulating effects of VKA on subclinical markers of cardiovascular disease. Conclusions These data demonstrate negative effects of VKA on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long-term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.

Management of Oral Anti-Coagulation in Patients with Heart Failure-Insights from the ThrombEVAL Study.

Patients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

Associations between degree and sub-dimensions of depression and metabolic syndrome (MetS) in the community: results from the Gutenberg Health Study (GHS).

BACKGROUND: A growing number of studies have associated metabolic syndrome (MetS) and depression, both retrospectively and prospectively. However, it has remained unclear, which degrees, or sub-dimensions of depression are related to MetS and if comorbid depression affects health care utilization. The purpose of the study was to determine the associations of a) somatic and cognitive-affective symptoms to MetS and b) depression and MetS to health care utilization. METHODS: In a population-based, representative survey of 14.499 participants we studied the associations of the two dimensions of depression with MetS and health care utilization. Depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). RESULTS: MetS and its components were associated with the degree of depression, particularly with moderately severe/ severe depressive symptoms (PHQ-9 > = 15). There were clear positive associations of somatic-affective depressive symptoms with the presence of MetS and its components. Cognitive-affective symptoms were negatively associated with MetS. At the single item level, disorders of sleep and appetite as well as exhaustion were positively, while trouble concentrating was negatively associated with MetS. Symptoms of depression were related to higher consultations of somatic and mental health care, while the presence of MetS was related to somatic health care utilization. There was an additional interaction of depressive symptoms and MetS with mental health care. CONCLUSIONS: Somatic affective symptoms of depression are positively associated, while cognitive-affective symptoms are negatively associated with MetS.

[Assessing incident cardiovascular and metabolic diseases in epidemiological cohort studies in Germany]. / Erfassung inzidenter kardiovaskulärer und metabolischer Erkrankungen in epidemiologischen Kohortenstudien in Deutschland.

BACKGROUND: Cardiovascular and metabolic diseases are a major cause of mortality and loss of quality of life in Germany. Research into risk factors of these diseases requires large population-based cohort studies. Complete and accurate assessment of the incidence of cardiovascular and metabolic diseases is a key element for valid interpretation of the results from such studies. OBJECTIVE: Our aim was to identify population-based cohort studies with incidence of cardiovascular and metabolic diseases in Germany and to summarize their methods for assessment and classification of disease endpoints, including myocardial infarction, type 2 diabetes, stroke, heart failure, and arterial hypertension. METHODS: Within the framework of a workshop, representatives of the ascertained population-based cohort studies in Germany with incidence of cardiovascular or metabolic diseases were invited to present and to systematically provide information on their methods of endpoint identification. RESULTS: We identified eight studies from different regions in Germany with a total of 100,571 participants, aged 18-83 years at baseline. Self-reporting by study participants is the major source for further inquiries to assess disease endpoints in these studies. Most studies use additional data sources to verify the incidence of diseases, such as documents provided by the treating physician or hospital. CONCLUSIONS: Our results highlight the central role of self-reporting and the efforts associated with identification and verification of disease endpoints in cohort studies. They also provide a basis for future population-based studies that aim for standardized assessment of the incidence of cardiovascular and metabolic diseases.

Emotional and tangible social support in a German population-based sample: Development and validation of the Brief Social Support Scale (BS6).

Aim of the study was the development and validation of the psychometric properties of a six-item bi-factorial instrument for the assessment of social support (emotional and tangible support) with a population-based sample. A cross-sectional data set of N = 15,010 participants enrolled in the Gutenberg Health Study (GHS) in 2007-2012 was divided in two sub-samples. The GHS is a population-based, prospective, observational single-center cohort study in the Rhein-Main-Region in western Mid-Germany. The first sub-sample was used for scale development by performing an exploratory factor analysis. In order to test construct validity, confirmatory factor analyses were run to compare the extracted bi-factorial model with the one-factor solution. Reliability of the scales was indicated by calculating internal consistency. External validity was tested by investigating demographic characteristics health behavior, and distress using analysis of variance, Spearman and Pearson correlation analysis, and logistic regression analysis. Based on an exploratory factor analysis, a set of six items was extracted representing two independent factors. The two-factor structure of the Brief Social Support Scale (BS6) was confirmed by the results of the confirmatory factor analyses. Fit indices of the bi-factorial model were good and better compared to the one-factor solution. External validity was demonstrated for the BS6. The BS6 is a reliable and valid short scale that can be applied in social surveys due to its brevity to assess emotional and practical dimensions of social support.

Loneliness in the general population: prevalence, determinants and relations to mental health.

BACKGROUND: While loneliness has been regarded as a risk to mental and physical health, there is a lack of current community data covering a broad age range. This study used a large and representative German adult sample to investigate loneliness. METHODS: Baseline data of the Gutenberg Health Study (GHS) collected between April 2007 and April 2012 (N = 15,010; 35-74 years), were analyzed. Recruitment for the community-based, prospective, observational cohort study was performed in equal strata for gender, residence and age decades. Measures were provided by self-report and interview. Loneliness was used as a predictor for distress (depression, generalized anxiety, and suicidal ideation) in logistic regression analyses adjusting for sociodemographic variables and mental distress. RESULTS: A total of 10.5% of participants reported some degree of loneliness (4.9% slight, 3.9% moderate and 1.7% severely distressed by loneliness). Loneliness declined across age groups. Loneliness was stronger in women, in participants without a partner, and in those living alone and without children. Controlling for demographic variables and other sources of distress loneliness was associated with depression (OR = 1.91), generalized anxiety (OR = 1.21) and suicidal ideation (OR = 1.35). Lonely participants also smoked more and visited physicians more frequently. CONCLUSIONS: The findings support the view that loneliness poses a significant health problem for a sizeable part of the population with increased risks in terms of distress (depression, anxiety), suicidal ideation, health behavior and health care utilization.

Depression, anxiety and suicidal ideation among 1(st) and 2(nd) generation migrants - results from the Gutenberg health study.

BACKGROUND: Even though migrants constitute a large proportion of the German population, there is a lack of representative studies on their mental health. Hence, the present study explored mental health characteristics and suicidal ideation comparing 1(st) and 2(nd) generation migrants to non-migrants and subgroups within 1(st) generation migrants. METHODS: We investigated cross-sectional data of 14,943 participants of the Gutenberg Health Study (GHS), a population-based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Migration status was assessed according to the German microcensus criteria. Depression and anxiety were measured by the PHQ (PHQ-8, GAD-2, Panic module), social anxiety by the Mini SPIN and Distressed Personality (Type D) by the DS-14. Suicidal ideation was assessed by the single item of the PHQ-9. RESULTS: A total of n = 3,525 participants had a migration background; the proportion of 1(st) generation (immigrated after 1949) migrants was 10.6 % (2(nd) generation 13 %). Among the 1(st) generation migrants those with Polish (N = 295) and Turkish (N = 141) origins were the largest groups from single countries. Controlling for sex, age and socioeconomic status, 1(st) generation migrants reported significantly more depression (OR 1.24; CI 1.01-1.52), generalized anxiety (OR 1.38; CI 1.13-1.68), panic attacks in the past 4 weeks (OR 1.43; CI 1.16-1.77); Type D (OR 1.28; CI 1.13-1.45) and suicidal ideation (1.44; CI 1.19-1.74) compared to non-migrants. The mental health of 2(nd) generation migrants did not differ from native Germans; they had the highest socioeconomic status of the three groups. Compared to native Germans, Turkish migrants of both sexes reported more depression and panic, particularly a strongly increased suicidal ideation (OR 3.02; CI 1.80-5.04) after taking sex, age, and socioeconomic status into account. Polish migrants only reported an increased rate of suicidal ideation and Type D. Turkish migrants exceeded Polish migrants regarding depression (OR = 2.61; 95 % CI 1.21-5.67), and panic attacks (OR=3.38; 95 % CI 1.45-7.85). In the subgroup analyses years lived in Germany was not significant. CONCLUSIONS: One of few representative community studies shows that compared to native Germans depression, anxiety and suicidal ideation were more frequently reported by 1(st) generation migrants, particularly of Turkish origin. Overall, 2(nd) generation migrants appear to have adjusted successfully. Limitations refer to a lack of data for persons without German language skills and missing mental health data in the Turkish sample. Further analyses need to address causes of mental strains and health care needs and provision.

Noise Annoyance Is Associated with Depression and Anxiety in the General Population- The Contribution of Aircraft Noise.

BACKGROUND: While noise annoyance has become recognized as an important environmental stressor, its association to mental health has hardly been studied. We therefore determined the association of noise annoyance to anxiety and depression and explored the contribution of diverse environmental sources to overall noise annoyance. PATIENTS AND METHODS: We investigated cross-sectional data of n = 15.010 participants of the Gutenberg Health Study (GHS), a population-based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Noise annoyance was assessed separately for road traffic, aircraft, railways, industrial, neighborhood indoor and outdoor noise ("during the day"; "in your sleep") on 5-point scales ("not at all" to "extremely"); depression and anxiety were assessed by the PHQ-9, resp. GAD-2. RESULTS: Depression and anxiety increased with the degree of overall noise annoyance. Compared to no annoyance, prevalence ratios for depression, respectively anxiety increased from moderate (PR depression 1.20; 95%CI 1.00 to 1.45; PR anxiety 1.42; 95% CI 1.15 to 1.74) to extreme annoyance (PR depression 1.97; 95%CI 1.62 to 2.39; PR anxiety 2.14; 95% CI 1.71 to 2.67). Compared to other sources, aircraft noise annoyance was prominent affecting almost 60% of the population. INTERPRETATION: Strong noise annoyance was associated with a two-fold higher prevalence of depression and anxiety in the general population. While we could not relate annoyance due to aircraft noise directly to depression and anxiety, we established that it was the major source of annoyance in the sample, exceeding the other sources in those strongly annoyed. Prospective follow-up data will address the issue of causal relationships between annoyance and mental health.

Hypertension in Germany.

BACKGROUND: Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. METHODS: Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. RESULTS: After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group. CONCLUSION: New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.

History of deep vein thrombosis is a discriminator for concomitant atrial fibrillation in pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is the consequence of deep vein thrombosis (DVT) in 70% of all cases. Although, PE and DVT are commonly related to risk factors of Virchow's triad, both entities are linked to cardiovascular risk factors, but risk factors seem differently important in both entities. OBJECTIVES: We aimed to investigate clinical profile and outcome of patients with PE history stratified by concomitant DVT. PATIENTS/METHODS: Data from the observational multi-center thrombEVAL-study were analyzed. RESULTS: The sample (N=2,318) comprised 295 PE patients, of whom 69.2% (N=204) had DVT. Individuals without DVT were older and had higher prevalence of concomitant atrial fibrillation (AF), chronic lung diseases, coronary artery disease, heart failure and hypertension. Multivariable regression revealed an independent association of AF (Odds Ratio (OR) 3.17, 95% CI 1.63-6.18, P<0.001) and coronary artery disease (OR 2.31, 95% CI 1.15-4.66, P=0.019) with PE without DVT. There was higher frequency of permanent AF in individuals without DVT, whereas paroxysmal AF was more prevalent in individuals with DVT. All AF subtypes were independently associated with PE without DVT with increasing ORs from paroxysmal to permanent AF. PE patients with and without DVT did not differ in survival (P=0.32) and cost-relevant clinical outcome (P=0.26) during follow-up. AF in PE patients was associated with cost-relevant clinical outcome (Hazard Ratio (HR) 1.78, 95% CI 1.03-3.09, P=0.040), but no significant difference in survival (HR 0.93, 95% CI 0.35-2.50, P=0.88) was observed. CONCLUSIONS: History of DVT is a significant discriminator for clinical profile of PE patients. Individuals without DVT had more often cardiac and pulmonary disease with strongest association with AF. Data advocate a potential link between AF and PE. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov, Unique identifier NCT01809015.