Gutenberg Health Study Research Articles

Incidence of type 2 diabetes by occupation – 10-year follow-up of the Gutenberg Health Study

Abstract Background In order to implement targeted type 2 diabetes (T2D) prevention measures for the workplace, it is important to identify high-risk occupations. Most previous studies examine the association between T2D and occupation cross-sectionally, but longitudinal studies are missing. This study aims to investigate the 10-year incidence of T2D in the working population of a German cohort and identify occupations with an increased risk. Methods Data from the population-based Gutenberg Health Study (GHS) were used to examine occupation at baseline (2007-2012) and T2D incidence at the 10-year follow-up. Occupational phases were coded into categories according to the KldB 2010. T2D was defined as either a physician-diagnosed T2D, HbA1c-level ≥6.5% or use of antidiabetic drugs. Age- and sex-standardised incidence and 95% confidence intervals (CI) were calculated for occupational groups based on the age- and sex-distribution of the German population. Standardised incidence ratios (SIR) and 95% CI were calculated using the incidence in the total GHS working population as the reference. Results Of 8130 workers at baseline, 45.2% were female, the mean age was 48.4 years and 4.5% had prevalent T2D. 388 cases occurred between baseline and the 10-year follow-up within the subgroup of persons without prevalent T2D at baseline and with follow-up data (n = 5954). The standardised incidence was 6.9%. “Food production and processing” (20.7%), “cleaners” (16.5%) and “drivers and mobile plant operators” (14.8%) had the highest standardised incidences. Compared to the total working population, we observed a threefold increased SIR for employees in “food production and processing” (3.0, 95% CI 1.8-4.7) and a two times higher SIR for “cleaners” (2.2, 95% CI 1.0-4.7) and “drivers and mobile plant operators” (2.2, 95% CI 1.3-3.3). Conclusions We identified occupations with an increased risk of T2D. Preventive measures and etiological research on work-related risks should focus on these occupations. Key messages • The highest standardised incidence was observed in the occupational groups “food production and processing”, “cleaners” and “drivers and mobile plant operators”. • Targeted prevention measures for type 2 diabetes in the workplace should focus on these occupational groups with increased incidence.

Assessment of psychological resilience in a large cohort of the general population: Validation and norm values of the RS-5.

Psychological resilience is known as a protective factor against mental health disorders for which valid measures are indispensable. The present work aims to evaluate the Resilience Scale-5 (RS-5) psychometrically, and provide norm values. Data from the Gutenberg Health Study (GHS), encompassing 7,496 participants aged 25 to 86, spanning the years 2017 to 2022, was used. Selectivity, item difficulty, internal consistency, construct and factor validity, as well as factorial invariance were tested. Additionally, correlations and associations with depression, anxiety, and sociodemographic factors were determined. Furthermore, norm values were provided. The RS-5 displayed robust psychometric properties. Participants reported an average resilience score of 28.94 (SD = 5.53, median = 30, IQR = 6, range = 5-35), with those aged ≥75 exhibiting the highest resilience levels (M = 30.21, SD = 5.75, median = 32, IQR = 7). The RS-5 displayed a very good model fit, affirming measurement invariance across sex and age decades. Construct validity found support through anticipated intercorrelations with related psychological constructs. Significant correlations (p < .001) linked higher resilience with female gender, advanced age, higher education, elevated household income, and diminished psychological distress. The RS-5 emerged as a reliable and economic instrument for assessing psychological resilience in individuals aged 25 to 86. The study unraveled distinct sociodemographic characteristics significantly tied to resilience levels within this cohort. In contributing recent norm values tailored to the German population, this research enhances the practical applicability of the RS-5 across diverse contexts and enriches our comprehension of the demographic nuances associated with psychological resilience.

Change of self-rated physical health predicts mortality in aging individuals: results of a population-based cohort study

BackgroundSelf-rated physical health (SRPH) is known as an important predictor of mortality. Previous studies mostly used baseline values of self-rated health to predict long-term mortality. The effect of change in self-rated physical health on mortality during the course of aging has rarely been researched. The present study aimed to determine SRPH over time in women and men of an aging population, assess whether and how change in SRPH affects mortality while adjusting for known determinants of mortality, and test effect modification by sex on the relation between course of SRPH and mortality.MethodsData of N = 12,423 respondents of the 5-year follow-up of the Gutenberg Health Study (GHS) with participation at the baseline assessment were analysed. All-cause mortality from 5-year follow-up onwards was defined as the primary outcome. SRPH was assessed by a single item. Cox proportional hazards models with adjustment for age, sex, socio-economic status and physical diseases were fitted to assess the predictive power of baseline score and course of SRPH. Additionally, effect modification by sex was assessed.ResultsDuring a median follow-up period of 7.3 years (quartiles 6.0-8.5 years), 618 (5%) participants died. Overall, 70.9% of the participants indicated good or very good SRPH at baseline (T1) and follow-up (T2), 6.9% rated their SRPH as not so good at T1 and T2, and 0.6% reported bad SRPH at T1 and T2. An improvement of SRPH was indicated by 9.6% and 12.0% indicated deterioration of their SRPH. Change in SRPH added substantial predictive information to the Cox proportional hazards models, when adjusting for relevant covariates. In men, deterioration and constantly bad SRPH were associated with the strongest increase in risk of mortality by 87%, resp. 228%. While improvements increased mortality risk in men (67%), women with an improved SRPH had a lower risk (57%).ConclusionA sizeable subgroup of aging participants reported deterioration of SRPH over five years. The association between change of SRPH and mortality is modified by sex. Deterioration of SRPH predicts mortality over baseline-assessment even when adjusted for relevant covariates. SRPH should be assessed regularly as part of an older individual’s health evaluation. Deterioration, constantly bad and improved SRPH should be taken seriously as unfavorable prognostic indicators, the latter only in men.

Prevalence of current suicidal thoughts and lifetime suicide attempts in individuals with cancer and other chronic diseases in Germany: Evidence for differential associations from a representative community cohort

BackgroundResearch indicates an elevated risk for suicidal thoughts and behaviors (STBs) among individuals with cancer, but community-based studies on the prevalence of STBs in comparison to the general population and other chronic diseases are lacking. MethodsData was drawn from the representative population-based, prospective Gutenberg Health Study (GHS). Participants (N = 12,382; age: M = 59.5, SD = 10.8; 48.9 % women) completed highly standardized medical assessments and validated questionnaires such as the PHQ-9. In addition to prevalence estimates (stratified by STBs and gender), logistic regression models were calculated (controlling for confounders). ResultsThe sample included 1910 individuals with cancer, 8.2 % of whom reported current suicidal thoughts and 2.0 % reported lifetime suicide attempts. There was neither a significant association between a cancer diagnosis and suicidal thoughts (p = .077) nor suicide attempts (p = .17) in models adjusting for age, gender, and income. Other chronic diseases were linked to suicidal thoughts and attempts only in men. LimitationsAlthough the investigation of the two kinds of STB are a strength of the study, the items' different time frames complicate comparisons. In addition, the cross-sectional design limits the ability to understand observed relationships and to identify periods of risk. ConclusionThis study expands the evidence base regarding the vulnerability to STBs in individuals with cancer, including long-term survivors. It highlights their heterogeneity, differential risk factors underlying suicidal thoughts and attempts, and the relevance of other (contextual) factors shaping an individual's susceptibility to suicidal crises.

Hypertensive Retinopathy is Not Associated with Low or High Birth Weight – Results from the Population-Based German Gutenberg Health Study

Hypertensive Retinopathy is Not Associated with Low or High Birth Weight – Results from the Population-Based German Gutenberg Health Study

Cardiovascular and genetic determinants of platelet high responsiveness: results from the Gutenberg Health Study

Cardiovascular and genetic determinants of platelet high responsiveness: results from the Gutenberg Health Study

Obesity-related inflammatory protein signature in cardiovascular clinical outcomes: results from the Gutenberg Health Study.

The objective of this study was to investigate whether an obesity-related inflammatory protein signature (OIPS) is associated with adverse cardiovascular events. The Olink Target 96 Inflammation panel was performed in 6662 participants from the population-based Gutenberg Health Study (GHS). The OIPS was selected by a logistic regression model, and its association with cardiovascular outcomes was evaluated by Cox regression analysis. The GHS-derived OIPS was externally validated in the MyoVasc study. The identified OIPS entailed 21 proteins involved in chemokine activity, tumor necrosis factor (TNF) receptor binding, and growth factor receptor binding. The signature revealed a novel positive association of axis inhibition protein 1 with obesity. The OIPS was associated with increased risk of all-cause and cardiac deaths, major adverse cardiovascular events, and incident coronary artery disease, independent of clinical covariates and established risk instruments. A BMI-stratified analysis confirmed the association of OIPS with increased death in those with obesity and overweight and with increased risk for coronary artery disease in those with obesity. The association of OIPS with increased risk of all-cause and cardiac deaths was validated in the MyoVasc cohort. The OIPS showed a significant association with adverse clinical outcomes, particularly in those with overweight and obesity, and represents a promising tool for identifying patients at higher risk for worse cardiovascular outcomes.

Noise annoyance due to different sources is associated with tinnitus presence and distress in the general population.

The pathophysiology of tinnitus is not yet fully understood. Although there is a large amount of evidence associating traffic noise exposure with non-auditory health outcomes, there is no evidence regarding the impact of noise annoyance on auditory disorders such as tinnitus. Thus, we aimed to investigate the association between noise annoyance due to different sources and tinnitus presence and distress in the general population. Data of 6813 participants from a large German population-based cohort were used (Gutenberg Health Study). Participants were asked about the presence of tinnitus and how much they were bothered by it. In addition, information on annoyance from road traffic, aircraft, railways, industrial, and neighborhood noise during the day and sleep was collected through validated questionnaires. The prevalence of tinnitus was 27.3%, and the predominant sources of noise annoyance in these subjects were aircraft, neighborhood, and road traffic noise. Overall, logistic regression results demonstrated consistent positive associations between annoyance due to different noise sources and prevalent risk of tinnitus with increases in odds ratios ranging from 4 to 11% after adjustment for sex, age, and socioeconomic status. Likewise, consistent increases in odds ratios were observed for tinnitus distress in subjects with prevalent tinnitus. For instance, neighborhood noise annoyance during the sleep was associated with a 26% increase in tinnitus distress (OR 1.26, 95% CI 1.13; 1.39). This is the first study investigating the association between noise annoyance and tinnitus presence and distress in a large cohort of the general population. Our results indicate consistent and positive associations between various sources of noise annoyance and tinnitus. These unprecedented findings are highly relevant as noise annoyance and tinnitus are widespread. The precise etiology and locus of tinnitus remain unknown, but excessive noise exposure is thought to be among the major causes. This study suggests that transportation and neighborhood noise levels thought merely to contribute to annoyance and non-auditory health effects may be sufficient to cause or exacerbate tinnitus.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on β-blockers than control subjects.

Impact of depersonalization on the course of depression: longitudinal observations from the gutenberg health study

BackgroundSymptoms of depersonalization (DP) and derealization (DR) are a risk factor for more severe impairment, non-response to various treatments, and a chronic course. In this study, we investigated the effects of DP/DR symptoms in patients with clinically significant depressive symptoms on clinical characteristics and various outcomes in a representative population-based sample with a 5-year follow-up.MethodsThe middle-aged sample comprised n = 10,422 persons at baseline, of whom n = 9,301 were free from depressive and DP/DR symptoms. N = 522 persons had clinically significant depression (PHQ-9 ≥ 10) and co-occurring DP/DR symptoms, and n = 599 persons had clinically significant depression (PHQ-9 ≥ 10) without DP/DR symptoms.ResultsThere were substantial health disparities between persons with and without depression. These disparities concerned a wide range of life domains, including lower quality of the recalled early life experiences with the parents, current socioeconomic status, social integration (partnership, loneliness), current social and interpersonal stressors (family, work), functional bodily complaints (e.g., tinnitus, migraine, chest pain), unhealthy lifestyle, and the prevalence of already developed physical diseases. These disparities persisted to the 5-year follow-up and were exceptionally severe for depressed persons with co-occurring DP/DR symptoms. Among the depressed persons, the co-occurrence of DP/DR symptoms more than doubled the risk for recurrence or persistence of depression. Only 6.9% of depressed persons with DP/DR symptoms achieved remission at the 5-year follow-up (PHQ-9 < 5). Depression with and without co-occurring DP/DR worsened self-rated physical health significantly. The impact of depression with co-occurring DP/DR on the worsening of the self-rated physical health status was stronger than those of age and major medical diseases (e.g., heart failure). However, only depression without DP/DR was associated with mortality in a hazard regression analysis adjusted for age, sex, and lifestyle.ConclusionsThe results demonstrated that DP/DR symptoms represent an important and easily assessable prognostic factor for the course of depression and health outcomes. Given the low remission rates for depression in general and depression with DP/DR in particular, efforts should be made to identify and better support this group, which is disadvantaged in many aspects of life.

Noise annoyance and cardiovascular disease risk: results from a 10-year follow-up study

The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p < 0.0001). While in the 10-year follow-up, mostly positive associations (although not significant) between noise annoyance and incident CVD were observed, no indication of increased CVD risk was observed after 5 years of follow-up. Noise annoyance due to different sources was associated with prevalent CVD, whereas only weak associations with incident CVD were found. Further large-scale studies are needed to establish the relationship between noise annoyance and risk of CVD.

Bi-Gaussian analysis reveals distinct education-related alterations in spherical equivalent and axial length—results from the Gutenberg Health Study

PurposeThe aim of this study is to investigate the distribution of spherical equivalent and axial length in the general population and to analyze the influence of education on spherical equivalent with a focus on ocular biometric parameters.MethodsThe Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Participants underwent comprehensive ophthalmologic examinations as part of the 5-year follow-up examination in 2012–2017 including genotyping. The spherical equivalent and axial length distributions were modeled with gaussian mixture models. Regression analysis (on person-individual level) was performed to analyze associations between biometric parameters and educational factors. Mendelian randomization analysis explored the causal effect between spherical equivalent, axial length, and education. Additionally, effect mediation analysis examined the link between spherical equivalent and education.ResultsA total of 8532 study participants were included (median age: 57 years, 49% female). The distribution of spherical equivalent and axial length follows a bi-Gaussian function, partially explained by the length of education (i.e., < 11 years education vs. 11–20 years). Mendelian randomization indicated an effect of education on refractive error using a genetic risk score of education as an instrument variable (− 0.35 diopters per SD increase in the instrument, 95% CI, − 0.64–0.05, p = 0.02) and an effect of education on axial length (0.63 mm per SD increase in the instrument, 95% CI, 0.22–1.04, p = 0.003). Spherical equivalent, axial length and anterior chamber depth were associated with length of education in regression analyses. Mediation analysis revealed that the association between spherical equivalent and education is mainly driven (70%) by alteration in axial length.ConclusionsThe distribution of axial length and spherical equivalent is represented by subgroups of the population (bi-Gaussian). This distribution can be partially explained by length of education. The impact of education on spherical equivalent is mainly driven by alteration in axial length.

Current and past depression as risk factors for incident type 2 diabetes mellitus and pre-diabetes in men and women: evidence from a longitudinal community cohort

BackgroundDepression is associated with an increased risk for type 2 diabetes mellitus. However, depression may take different courses, and it is not fully understood how these affect the development of diabetes. It is further to be determined whether sex modifies the association between depression and type 2 diabetes.MethodsWe analyzed data from the Gutenberg Health Study, a longitudinal and population-based cohort study (N = 15,010) in Germany. Depressive symptoms (measured by PHQ-9), history of depression, diabetes mellitus, and relevant covariates were assessed at baseline, and the outcomes of prediabetes and type 2 diabetes mellitus were evaluated 5 years later. Logistic regression was used to estimate odds ratios of incident prediabetes and type 2 diabetes mellitus, adjusting for potential confounders as identified in a Directed Acyclic Graph.ResultsIn the confounder adjusted model, current depression (PHQ-9 ≥ 10 at baseline; OR = 1.79, 95% CI = 1.11 to 2.74, p = 0.011), and persistent depression had a statistically significant (OR = 2.44, 95% CI = 1.62 to 3.54, p = 0.005) effect on incident type 2 diabetes mellitus. A history of depression without current depression had no statistically significant effect on type 2 diabetes (OR = 1.00, 95% CI = 0.68 to 1.43, p = 0.999). The effect of depression on incident diabetes did not differ significantly between women (OR = 2.02; 95% CI = 1.32 to 3.09) and men (OR = 2.16; 95% CI = 1.41 to 3.31; p-value for interaction on the multiplicative scale p = 0.832 and on the additive scale p = 0.149). Depression did not have a significant effect on incident prediabetes.ConclusionThis study shows how the history and trajectory of depression shape the risk for diabetes. This raises interesting questions on the cumulative effects of depression trajectories on diabetes and body metabolism in general. Depression can negatively affect physical health, contributing to increased morbidity and mortality in people with mental disorders.

Night shift work and cardiovascular diseases among employees in Germany: five-year follow-up of the Gutenberg Health Study.

This study aimed to determine if there is an increased risk of incident cardiovascular diseases (CVD) resulting from cumulative night shift work in the German population-based Gutenberg Health Study (GHS). We examined working participants of the GHS at baseline and after five years. Cumulative night shift work in the 10 years before baseline was assessed and categorized as low (1-220 nights ≙ up to 1 year), middle (221-660 nights ≙ 1-3 years), and high (>660 nights ≙ more than 3 years) night shift exposure. Hazard ratios (HR) were estimated for incident "quality-assured CVD events" using Cox proportional hazard models. At baseline, 1092 of 8167 working participants performed night shift work. During the follow-up, 202 incident cardiovascular events occurred. The crude incidence rates for CVD per 1000 person-years were 6.88 [95% confidence interval (CI) 4.80-9.55] for night shift workers and 5.19 (95% CI 4.44-6.04) for day workers. Cumulative incidence curves showed a higher cumulative incidence in workers exposed to night shift work compared to day workers after five years. The adjusted HR for incident CVD events were 1.26 (95% CI 0.68-2.33), 1.37 (95% CI 0.74-2.53) and 1.19 (95% CI 0.67-2.12) for employees in the low, middle and high night shift categories compared to employees without night shift work, respectively. The observed tendencies indicate that night shift work might be negatively associated with cardiovascular health. We expect the continued follow-up will clarify the long-term impact of night shift work.

Change of Intraocular Pressure Over 5 Years and its Relationship to Cardiovascular Parameters: Results From the Gutenberg Health Study.

To investigate the longitudinal change in intraocular pressure (IOP) over 5 years and its relationship with cardiovascular parameters in a population-based sample in Germany. The Gutenberg Health Study is a prospective, observational, single-center cohort study. The sample was equally stratified for sex, residence, and age decade. IOP was measured with noncontact tonometry at baseline and at 5-year follow-up. Cardiovascular parameters, including body mass index (BMI), systolic blood pressure, and diabetes status, were assessed. Participants without IOP measurement at one time point, who were taking IOP-lowering medications, or who had ophthalmic surgery during the 5-year follow-up interval were excluded, as well as those with glaucoma diagnosis. Univariable and multivariable linear regression analyses were conducted. This analysis included 9633 participants (48.9% female). The mean IOP increased from 14.04 ± 2.78 mmHg at baseline to 14.77 ± 2.92mmHg at 5-year follow-up (P < 0.001). In multivariable linear regression analyses, an increase in BMI was associated with an increase in IOP over time (P < 0.001), whereas a higher baseline BMI was associated with a lower IOP change (P < 0.001). Higher age and male sex were associated with higher IOP change (P < 0.001). A change in systolic blood pressure was associated with IOP change, whereas baseline systolic blood pressure and diabetes status were not associated. This population-based study found a relationship between IOP change over 5 years and BMI and systolic blood pressure change, respectively. These findings suggest the importance of monitoring cardiovascular risk factors in IOP management.

Age standardization and time-of-day performance for the Oldenburg Sentence Test (OLSA): results from the population-based Gutenberg Health Study

PurposeThe Oldenburg Sentence Test (OLSA) is a German matrix test designed to determine speech recognition thresholds (SRT). It is widely used for hearing-aids and cochlear implant fitting, but an age-adjusted standard is still lacking. In addition, knowing that the ability to concentrate is an important factor in OLSA performance, we hypothesized that OLSA performance would depend on the time of day it was administered. The aim of this study was to propose an age standardization for the OLSA and to determine its diurnal performance.MethodsThe Gutenberg Health Study is an ongoing population-based study and designed as a single-centre observational, prospective cohort study. Participants were interviewed about common otologic symptoms and tested with pure-tone audiometry and OLSA. Two groups—subjects with and without hearing loss—were established. The OLSA was performed in two runs. The SRT was evaluated for each participant. Results were characterized by age in 5-year cohorts, gender and speech recognition threshold (SRT). A time stamp with an hourly interval was also implemented.ResultsThe mean OLSA SRT was − 6.9 ± 1.0 dB (group 1 male) and − 7.1 ± 0.8 dB (group 1 female) showing an inverse relationship with age in the whole cohort, whereas a linear increase was observed in those without hearing loss. OLSA-SRT values increased more in males than in females with increasing age. No statistical significance was found for the diurnal performance.ConclusionsA study with 2900 evaluable Oldenburg Sentence Tests is a novelty and representative for the population of Mainz and its surroundings. We postulate an age- and gender-standardized scale for the evaluation of the OLSA. In fact, with an intergroup standard deviation (of about 1.5 dB) compared to the age dependence of 0.7 dB/10 years, this age normalization should be considered as clinically relevant.

MyD88 in myeloid cells promotes angiotensin II-induced vascular inflammation and is associated with all-cause mortality and incident heart failure in humans with arterial hypertension

Abstract Background Angiotensin II (AngII) causes hypertension and promotes vascular accumulation of inflammatory cells. We aimed to determine how myeloid factor of differentiation 88 (MyD88) contributes to vascular dysfunction and arterial hypertension in mice and humans. Methods Male C57BL/6 as well as MyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/- and TLR9-/- were investigated in the AngII-model of hypertension (1 mg/kg/d for 7days). Biodata analyses were performed in the Gutenberg-Health Study (GHS), a population based cohort. In addition, we performed computational analyses of known hypertension-related genes from genome-wide association studies (GWAS) to investigate whether they preferentially interact with MyD88 in the human protein network. Results MyD88 deficiency attenuated AngII-induced blood pressure increase and endothelial dysfunction in conductance and resistance vessels. Vascular mRNA expression levels of vcam-1, nos2, nox2 were decreased in AngII-infused MyD88-/- mice compared to C57BL/6 controls. Flow cytometric analyses revealed that AngII-induced aortic accumulation of CD11b+Ly6Chi inflammatory monocytes was significantly dampened in MyD88-/- mice. AngII increased mRNA expression of cd62L, cd68 and ccl2, which was blocked in MyD88-/- mice, indicating a role of MyD88 for myeloid cell activation and differentiation. Additionally, aortic interferon-g+ NK cells and mRNA levels of interleukin-12 and interleukin-1b were reduced in AngII-treated MyD88-/- mice. Bone marrow transfer experiments demonstrated a vasoprotective effect of MyD88 deficiency in bone marrow-derived cells, and selective expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myelomonocytic cells drives vascular dysfunction in a MyD88-dependent manner. Furthermore, data from 1,274 individuals in the GHS indicated, that MyD88 mRNA expression was associated with all cause mortality and incident chronic heart failure after a median follow-up of 11.6 years. Computational analysis of the human protein interaction network demonstrated that MyD88 is significantly connected to proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. Conclusion We provide evidence, that MyD88 expressed by myelomonocytic cells promotes AngII-induced vascular dysfunction and arterial hypertension. MyD88 might be used as an inflammatory diagnostic marker for the risk of death in hypertensive patients.

Sex differences in the clinical profile of individuals with prediabetes and type 2 diabetes mellitus in the general population - results from the Gutenberg Health Study

Abstract Introduction The rising prevalence of type 2 diabetes mellitus (T2DM) and concomitant diseases accompany mounting evidence of clinically significant sex differences. T2DM is more frequently diagnosed at lower ages in men, differences in biology and lifestyle affect risk and complications differently in both sexes, and risk for vascular disease was shown to be higher in women. Also, in prediabetes, sex differences were detected, but only a few studies exist. Purpose To investigate the sex-related prevalence of prediabetes and T2DM in the general population, the clinical profile regarding asymptomatic organ damage (AOD) and prevalent cardiovascular disease (CVD), and its influence on CVD risk prediction and mortality. Methods The Gutenberg Health Study sample (15,010 subjects, 35-74 years) was stratified regarding sex and glucose state. Euglycemia, prediabetes, and T2DM were categorized based on clinical information and HbA1c level. CVD included the prevalence of coronary artery disease, myocardial infarction, stroke or transient ischemic attack, heart failure, atrial fibrillation, and peripheral artery disease. AOD was assessed in individuals without prevalent CVD as an indicator of early, subclinical CVD according to current guidelines and included left ventricular mass index, carotid intima-media thickness and plaque, ankle-brachial index, and renal function. Ten years of CVD risk prediction was assessed using the Framingham score. Clinical outcome was assessed by structured follow-up. Results Overall, 14,870 individuals were included in the present analysis, 7,352 women and 7,518 men. Among them, 4,784 (65.1%) women and 4,642 (61.7%) men revealed euglycemia, 2,065 (28.1%) women and 2,063 (27.4%) men had prediabetes, and in 503 (6.8%) women and 813 (10.8%) men T2DM was present. Except for obesity, cardiovascular risk factors were more prevalent in prediabetic and diabetic men than in women. Female sex was associated with a reduced risk for AOD (prevalence ratio (PR) 0.92, 95% confidence interval (CI) 0.89 to 0.94, P&amp;lt;0.0001) and CVD (PR 0.65, 95%CI 0.59 to 0.71, P&amp;lt;0.0001). The 10-year risk for CVD was about doubled in men compared to women in euglycemia (women 6.8±6.2% vs. men 14.9±11.3%), prediabetes (women 11.6±7.8% vs. men 21.6±12.6%) and T2DM (women 24.7±12.9% vs. men 42.6±17.9%). Regarding all-cause mortality, female sex was favorable (hazard ratio 0.58, 95%CI 0.51 to 0.66, P&amp;lt;0.0001). Conclusions In the general population, euglycemia and prediabetes were more prevalent in women, T2DM was more prevalent in men. Distinct differences were found in risk between both sexes, with a more favorable profile in women. Particularly the high prevalence of the primarily unrecognized prediabetes in the general population highlights the necessity for prevention and early detection. Investigating sex-associated differences may help to elucidate the pathophysiology and improve prevention and treatment by more individualized therapy concepts.

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.

Vertigo and its burden of disease-Results from a population-based cohort study.

Vertigo describes symptoms of abnormal movement of the environment or the patient's own body. As such, it affects patients' quality of life, prevents them from following their daily activities, and increases healthcare utilization. The Global Burden of Disease Project aims to quantify morbidity and mortality worldwide. In 2013, a separate disability weight for vertigo was introduced. The aim of this study is to estimate the symptom burden of disease caused by vertigo. This study analyzes data from the Gutenberg Health Study (GHS). The GHS is a population-based cohort study representative of the city of Mainz and its district. Participants were asked whether they suffered from vertigo and, if so, how bothered they felt by it, rating their distress on a six-level scale from 1 = little stressful to 6 = extremely stressful. Eight thousand five hundred and nineteen participants could be included in the study. The overall prevalence of vertigo was 21.6% (95%-confidence interval [CI] [20.7%; 22.5%]). Vertigo prevalence peaked in the age group of 55-64 years. Vertigo annoyance averaged 2.42 (1.28). When an annoyance of 3-6 was considered bothersome, the prevalence of bothersome vertigo was 8.1 % (95%-CI [7.5%; 8.7%]). Age-standardized to the European Standard Population 2013, vertigo caused a burden of 2102 years lived with disability per 100,000 population. In this study, it was found that one in five people suffer at least occasionally from vertigo. This result suggests a significant burden of disease. This burden is reported at the symptom level. Future studies are needed to attribute the burden to specific causes. 2.