Gutenberg Health Study Research Articles

Midregional pro atrial natriuretic peptide: a novel important biomarker for noise annoyance-induced cardiovascular morbidity and mortality?

BackgroundEnvironmental noise exposure has been associated with increased cardiovascular morbidity and mortality. Recently, noise annoyance was shown to induce atrial fibrillation, which was accompanied by significantly increased levels of midregional pro atrial natriuretic peptide (MR-proANP). Therefore, the aim of the present study was to analyze the association between noise annoyance, MR-proANP, incident cardiovascular events, and all-cause mortality.MethodsLevels of MR-proANP were measured in the first 5000 participants of the population-based Gutenberg Health Study. Annoyance was assessed separately for aircraft, road traffic, railway, neighborhood, and industrial/construction noise during the day and sleep.ResultsIn cross-sectional analyses, aircraft noise annoyance during day and sleep, industrial/construction noise annoyance during day, and railway noise annoyance during sleep were independently associated with increased levels of MR-proANP after multivariable adjustment. After a 5-year follow-up period, there were 43 cases of incident atrial fibrillation and 103 of incident cardiovascular disease (comprising atrial fibrillation, coronary artery disease, myocardial infarction, heart failure, or stroke). Moreover, there were 301 deaths after a mean follow-up of 7.42 ± 1.66 years. An odds ratio (OR) of 2.82 ([95% confidence interval (CI) 1.86; 4.35], p < 0.0001) for incident atrial fibrillation and an OR of 1.49 ([95% CI 1.13; 1.96], p = 0.0046) for incident cardiovascular disease per 1-standard deviation (SD) increase in MR-proANP levels were found. A 36% (hazard ratio: 1.36 [95% CI 1.19; 1.55], p < 0.0001) higher risk of death was found per 1-SD increase in MR-proANP levels.ConclusionsNoise annoyance may contribute to cardiovascular morbidity and mortality and is characterized by increased levels of MR-proANP.Graphic abstract

No evidence for an association of plasma homocysteine levels and refractive error - Results from the population-based Gutenberg Health Study (GHS).

There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D--2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6 D, 3.5%). Median Hcy levels were similar in all groups (μmol/l). We observed no association of Hcy with refraction or 5-year change in refraction in the models adjusted for age, sex and socioeconomic status. We found no evidence for an association of Hcy levels and refractive error.

Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study

BackgroundIron deficiency is now accepted as an independent entity beyond anemia. Recently, a new functional definition of iron deficiency was proposed and proved strong efficacy in randomized cardiovascular clinical trials of intravenous iron supplementation. Here, we characterize the impact of iron deficiency on all-cause mortality in the non-anemic general population based on two distinct definitions.MethodsThe Gutenberg Health Study is a population-based, prospective, single-center cohort study. The 5000 individuals between 35 and 74 years underwent baseline and a planned follow-up visit at year 5. Tested definitions of iron deficiency were (1) functional iron deficiency—ferritin levels below 100 µg/l, or ferritin levels between 100 and 299 µg/l and transferrin saturation below 20%, and (2) absolute iron deficiency—ferritin below 30 µg/l.ResultsAt baseline, a total of 54.5% of participants showed functional iron deficiency at a mean hemoglobin of 14.3 g/dl; while, the rate of absolute iron deficiency was 11.8%, at a mean hemoglobin level of 13.4 g/dl. At year 5, proportion of newly diagnosed subjects was 18.5% and 4.8%, respectively. Rate of all-cause mortality was 7.2% (n = 361); while, median follow-up was 10.1 years. After adjustment for hemoglobin and major cardiovascular risk factors, the hazard ratio with 95% confidence interval of the association of iron deficiency with mortality was 1.3 (1.0–1.6; p = 0.023) for the functional definition, and 1.9 (1.3–2.8; p = 0.002) for absolute iron deficiency.ConclusionsIron deficiency is very common in the apparently healthy general population and independently associated with all-cause mortality in the mid to long term.Graphic abstract

Prevalence and new onset of depression and anxiety among participants with AMD in a European cohort

To investigate the prevalence and new onset of depression and anxiety among subjects with age-related macular degeneration (AMD) and its association with AMD in a large European cohort with relatively good visual acuity. 11,834 participants enrolled in the German population-based Gutenberg Health Study were studied. AMD was diagnosed by grading of fundus photographs. Depression and anxiety were assessed with the Patient Health Questionnaire and the Generalized Anxiety Disorder-2 Scale, respectively. Logistic regression analyses were performed and adjusted for several parameters. 1,089 (9.2%) participants were diagnosed having AMD. Prevalence of depression in AMD and non-AMD participants was 7.2% and 8.0%, respectively and prevalence of anxiety was 4.2% and 7.0%, respectively. New onset of depression and anxiety at 5-year follow-up in AMD subjects was 2.6% and 3.6%, respectively. AMD was not associated with depression (OR 0.93; CI 95% 0.70–1.20; p = 0.62). AMD was associated with less anxiety (OR 0.67; CI 95% 0.47–0.93; p = 0.02). This is the first study analyzing both prevalence and new onset of depression and anxiety in AMD subjects. AMD- and non-AMD participants had a similar prevalence and new onset of depression in our population-based sample. Participants without AMD had a higher prevalence of anxiety. AMD was not associated with depression.

Prevalence of Strabismus and Its Impact on Vision-Related Quality of Life: Results from the German Population-Based Gutenberg Health Study

This study investigates the prevalence of manifest strabismus and its subtypes in adulthood and analyzes the risk factors and its impact on vision-related quality of life (VRQoL). The Gutenberg Health Study (GHS) is a population-based, observational cohort study. A cross-sectional analysis of the baseline examination was conducted. Participants aged 35 to 74 years were included (n= 15 010). All participants were examined with a comprehensive ophthalmologic and general examination including the Hirschberg corneal reflex test to detect manifest strabismus. The following risk factors were analyzed: age, sex, socioeconomic status, birth weight, maternal age at birth, anisometropia, astigmatism, spherical equivalent, low visual acuity in the worse seeing eye (≥1.3 logMAR), and cardiovascular factors, and included in multivariable logistic regression analysis. Lifetime period prevalence and point prevalence of manifest strabismus were computed, and VRQoL was compared between participants with and without strabismus. Strabismus prevalence. A total of 14 700 participants (age, 55.0±11.1 years; 49.5% were female) were included in this analysis. The weighted prevalence of ever having strabismus was 2.9% (2.6%-3.2%), and the point prevalence for concomitant strabismus was 2.5% (2.3%-2.8%). Esotropia was twice as frequent as exotropia, and 2 participants had paralytic strabismus. Concomitant strabismus was associated with age 65 to 69 years (odds ratio [OR], 0.13 [0.05-0.39], P < 0.001); age 70 to 74 years (OR, 0.14 [0.05-0.4], P < 0.001); anisometropia (>1.0 diopters [D]: OR, 3.61 [2.32-5.62], P < 0.001; >2.0 D: OR, 6.93 [4.23-11.35], P < 0.001); astigmatism (≥1.0 D: OR, 2.09 [1.42-3.08], P < 0.001; ≥2.0 D: OR, 3.74 [2.35-5.97], P < 0.001); spherical equivalent (per diopter: OR, 1.43 [1.33-1.53], P < 0.001); and low visual acuity in the worse seeing eye (≥1.3 logMAR: OR, 21.7 [11.2-42.0], P< 0.001). VRQoL was lower in participants with strabismus compared with participants without strabismus in adjusted analysis (B=-5.96, P < 0.001). Strabismus is a frequent chronic eye condition that is associated with a lower VRQoL. Individuals with anisometropia, astigmatism, and hyperopia are more likely to have strabismus. In addition, low visual acuity in the worse eye was linked to strabismus prevalence.

Frequency of stressful life events and associations with mental health and general subjective health in the general population

AimWe aim to determine the frequency of stressful life events (SLEs) and investigate the association of single and aggregated SLEs with mental health and general subjective health, which has not been reported for an aging representative sample to date.Subjects and methodsA total of 12,947 participants (35–74 years old) of the Gutenberg Health Study (GHS) in Germany were analyzed. SLEs were analyzed at the item and aggregated level with unweighted and weighted sum scores. Additionally, the survey included measures of mental health, general subjective health and demographics. Descriptive analyses were stratified by sex, age and socioeconomic status.ResultsMultivariate analyses of variance with SLE at the item level revealed large main effects for sex (ηp2 = 0.30) and age (ηp2 = 0.30); a moderate effect was found for socioeconomic status (ηp2 = 0.08). Interaction effects of sex with age and SES were also significant, but with negligible effect sizes. Regression analyses revealed similar results for unweighted and weighted SLE sum scores controlling for sociodemographic variables, supporting the detrimental relations among cumulated SLEs, depression (β = 0.18/0.19) and anxiety (β =0.17/0.17), but not general health. Mental health indicators showed the highest correlations with single SLEs such as change of sleep habits or personal finances. Severe SLEs according to proposed weight scores showed no or only weak associations with mental health.ConclusionRepresentative data support a more distinct impact of SLEs on mental health than on general health. Single SLEs show strong associations with mental health outcome (e.g., change of sleep habits). The low associations between severe single SLEs and mental health merit further attention.

Noise annoyance predicts symptoms of depression, anxiety and sleep disturbance 5 years later. Findings from the Gutenberg Health Study

Cross-sectional studies have shown that noise annoyance is strongly associated with mental distress, however, its long-term effects on mental health is unknown. We therefore investigated whether noise annoyance predicts depression, anxiety and sleep disturbance in a large, representative sample 5 years later. We investigated longitudinal data of N = 11905 participants of the Gutenberg Health Study, a population-based, prospective, single-centre cohort study in mid-Germany (age at baseline 35-74 years). Noise annoyance was assessed at baseline and 5-year follow-up (sources: road traffic, aircraft, railways, industrial, neighbourhood indoor and outdoor noise; and day vs. nighttime). Depression, anxiety and sleep disturbance were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-2. Participants suffering from depression, anxiety or sleep disturbance at baseline were excluded from the respective multivariate analyses of new onset at follow-up. General noise annoyance remained stable. Daytime noise annoyance predicted new onset of depressive, anxiety symptoms (also nighttime annoyance) and sleep disturbance (beyond respective baseline scores). Additional predictors were female sex, lower age and low socioeconomic status (SES). Regarding specific sources, daytime baseline aircraft annoyance predicted depression and anxiety. Sleep disturbance was most consistently predicted by neighbourhood annoyance (baseline and follow-up) and follow-up annoyance by aircraft (night) and road traffic (day and night). We identified current and past noise annoyances as risk factors for mental distress and sleep disturbance. Furthermore, women, younger adults and those with lower SES are particularly susceptible to noise annoyance. Our results indicate the need to provide regulatory measures in affected areas to prevent mental health problems.

A multi-cohort consortium for GEnder-Sensitive Analyses of mental health trajectories and implications for prevention (GESA) in the general population in Germany

IntroductionMental health is marked by gender differences. We formed a multi-cohort consortium to perform GEnder-Sensitive Analyses of mental health trajectories and study their implications for prevention (GESA). GESA aims at...

Thrombin generation in cardiovascular disease and mortality - results from the Gutenberg Health Study.

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Cox regression models adjusted for age, sex, cardiovascular risk factors and vitamin K antagonists investigated the association between thrombin generation parameters and total mortality. Lag time was positively associated with obesity and dyslipidaemia for both sexes (P<0.0001). Obesity was also positively associated with endogenous thrombin potential in both sexes (P<0.0001) and peak height in males (1 pM tissue factor, P=0.0048) and females (P<0.0001). Cox regression models showed an increased mortality in individuals with lag time (1 pM tissue factor, hazard ratio=1.46, 95% confidence interval: 1.07-2.00; P=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio=1.50, 95% confidence interval: 1.06-2.13; P=0.023) above the 95th percentile of the reference group, independently of the cardiovascular risk profile. This large-scale study demonstrates that traditional cardiovascular risk factors, particularly obesity, are relevant determinants of thrombin generation. Lag time and endogenous thrombin potential were found to be potentially relevant predictors of increased total mortality, observations which deserve further investigation.

Association between medicated obstructive pulmonary disease, depression and subjective health: results from the population-based Gutenberg Health Study

Medicated obstructive pulmonary disease (asthma or COPD) has been associated with depression. Yet, there is little knowledge of the interplay of contributing social, biological, behavioral and psychological factors in the community. The study was conducted: (1) To determine the prevalence of depression in participants with medicated COPD or asthma from the general population, (2) to identify underlying social, biological, behavioral and psychological factors and (3) to determine the contribution of obstructive pulmonary disease and depression to subjective health. The population-based sample of 15.010 study participants (35–74 years) from the Gutenberg Health Study (GHS) was queried according to a medical diagnosis of obstructive pulmonary disease, defined as medicated COPD or asthma, and comorbid disorders. Demographic, behavioral and psychological factors were assessed by self-report; lung function (FEV1; FCV) was measured by spirometry. 307 men (4.3%) and 396 women (5.6%) reported a medical diagnosis of COPD or asthma. The prevalence of depression (PHQ-9 > = 10) was twice as high (16.2% vs. 7.5%) compared to participants without obstructive pulmonary disease. Participants with obstructive pulmonary disease were older, had a lower SES, more comorbid diseases and cardiovascular risk factors, higher distress and took more psychotropic medication. In multivariable logistic regression analyses, obstructive pulmonary disease was associated with a 71% increase of depression (OR = 1.71; 95% CI = 1.30 to 2.24). Additional contributors were FEV1 (1.18; 95% CI = 1.05 to 1.32) and dyspnea (NYHA > = 1) (2.19; 1.82 to 2.64), sex (women) (OR = 1.73; 95% CI 1.41 to 2.12), lower SES (OR = 0.98; 95%CI = 0.96 to 0.99). Lack of active sports OR = 0.79; 95% CI 0.68 to 0.92), obesity (OR 1.27; 95% CI 1.07 to 1.50), smoking (OR = 1.26; 95% CI 1.06 to 1.49) and dyslipidemia (OR = 1.35; 95% CI 1.15 to 1.57) also increased the risk of depression. Additional psychological risks were social phobia, type D, low social support, loneliness and life events in the past 12 months. In multivariable linear regression analyses, obstructive pulmonary disease and depression independently contributed to reduced subjective health in addition to sedentary behavior, smoking and comorbid somatic and mental disorders. These findings provide evidence that COPD and asthma are associated with depression in the community. Complex underlying demographic, medical and psychosocial variables have been identified which may justify an integrative treatment approach. Promoting health behavior (smoking cessation, exercising, weight reduction) and social integration may not only improve the somatic course of the disease, but also mental health. Mental health treatment may also improve health behavior and subjective health.

Course of depressive symptoms in men and women: differential effects of social, psychological, behavioral and somatic predictors

In this study, we aimed to identify the most important and sex-specific social, psychological, behavioral and somatic predictors of recurrent depressive symptoms. Data was obtained at two measurement points within five years by the Gutenberg Health Study (GHS). Out of N = 12,061 individuals, a sample of 877 (age 52.3 ± 9.9) who reported clinically relevant depressive symptoms at baseline was analyzed. Univariate analyses and multiple logistic regression analyses were conducted. Almost half of participants depressed at baseline also reported depressive symptoms five years later. Sex-stratified multivariate analyses revealed that solely social support remained a significant protective predictor against recurrence of depression in men (OR = 0.93; CI95% = 0.87–0.99), whereas in women smoking (OR = 1.97; CI95% = 1.23–3.22), and Type D personality (OR = 1.65; CI95% = 1.10–2.49) were significant risk factors. However, when analyzing the entire sample, no interaction effect between sex and each predictor turned out to be significant. Only social support was retained as an overall predictive factor. As depressive symptoms recur, depressive vulnerability is established involving personality, health behavior and social factors. Although no significant sex-specific interactions were observed, sex-stratified analyses point out different patterns for relevant predictors of recurrent depressive symptoms in men and women.

Low Birth Weight Is Linked to Age-Related Macular Degeneration: Results From the Population-Based Gutenberg Health Study (GHS).

This study analyzed whether low birth weight is linked to prevalence and incidence of age-related maculopathy (AMD) in adulthood. The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany. GHS participants at an age from 35 to 74 years were included. An ophthalmologic examination with fundus photography was carried out. Fundus photographs were graded according to the Rotterdam Grading Scheme for AMD at baseline and at the 5-year follow-up examination. Participants were divided into three different birth weight groups (low: <2500 g; normal: 2500-4000 g; and high: >4000 g). Poisson regression analysis with adjustment for several confounders was used to assess associations between birth weight and AMD prevalence (overall, early, late AMD) and 5-year cumulative incidence. Overall, 6492 participants were included (3538 female, aged 50.7 ± 10.4 years). Prevalence of total AMD was highest in the low birth weight group (11.2%; 40/358) compared to the normal birth weight group (6.5%; 346/5328) and the high birth weight group (8.4%; 68/806). Low birth weight was associated with overall AMD prevalence (prevalence ratio [PR] = 1.54, P = 0.006), and in particular with early AMD prevalence (PR = 1.52; P = 0.01). No association was observed between low birth weight and cumulative 5-year incidence of AMD. Our analyses indicate that low birth weight may lead to higher prevalence of retinal diseases in later life, as we observed for AMD. Our results are limited due to missing data and loss to follow-up, but may be a first hint that AMD has one of its origins in early life.

Schirmer test results: are they associated with topical or systemic medication?

PurposeTo test whether Schirmer test (ST) results are associated with topical or systemic medication and to evaluate the distribution of tear fluid quantity in a 3-min and 5-min ST. MethodsThe Gutenberg Health Study is a population-based, prospective, observational cohort study in Germany. ST was assessed in a sub-cohort of 1,999 participants. ST was performed under topical anesthesia for 5 min (ST-5) or of 3 min (ST-3). Anthropometric factors, systemic diseases, use of systemic and eye medications were recorded. We used multivariable quantile regression analysis to assess the influence on ST measurements. ResultsThe length of wetting of the Schirmer strips for ST-5 was 23.2 ± 9.31 mm for right and 22.9 ± 9.0 mm for left eyes. In ST-3, the measurements were 20.0 mm in right and 19.1 mm in left eyes. The clinical cut off of 10 mm for ST-5 corresponded with an 8 mm cut off for ST-3.There was an association of smaller ST-5 measures with male sex, higher age, socioeconomic status and season (all p < 0.001), but not with diabetes or smoking. The use of prostaglandin or beta-blocker eye drops or oral non-steroidal anti-inflammatory drugs, drugs for peptic ulcer and gastro-oesophageal reflux disease, thyroid hormones, progesterone and estrogen combination drugs, and hypnotics and sedatives showed an association with smaller ST-5. ConclusionsFor the first time we describe the distribution of tear fluid quantity by ST in a very large cohort of the general population. Furthermore, we found associations of ST measures with topical and systemic medication.

Characteristics and pathologies of the vitreo-macular interface-results from the Gutenberg Health Study.

We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. The Gutenberg Health Study is a population-based study in Germany, including an ophthalmological examination with refraction, biometry and optical coherence tomography (OCT) imaging. Characteristics of the vitreo-macular interface were graded on volume scans including visibility of an epiretinal membrane, full-thickness macular hole, lamellar hole and pseudohole. Overall and age-specific prevalences including 95% confidence intervals [95%-CI] were calculated. Association analyses were conducted to determine systemic and ocular factors that are associated with epiretinal membranes (the most common pathology) using multivariable logistic regression. A total of 1890 people aged 40-80years were included in the study. Of these, 4.7% (95%-CI: 3.8%-5.8%) had an epiretinal membrane in at least one eye, 0.1% a full-thickness macular hole, 0.6% a lamellar hole and 0.6% a pseudohole. The presence of an epiretinal membrane was associated with higher age, myopic refractive error and prior retinal laser therapy, but not with gender, body height, body weight, smoking, prior cataract surgery or intraocular pressure. Epiretinal membranes are more frequent in older and myopic subjects and in those with prior retinal laser therapy.

Intact Visuospatial Cognition in Amblyopia: Results From the Gutenberg Health Study.

To determine whether amblyopia interferes with cognitive functions requiring visuospatial processing, measured by the Tower of London (ToL) test. The current study was based on a sub-cohort from the population-based Gutenberg Health Study and included 1,569 participants aged 35 to 44 years. Amblyopia was defined as a visual acuity of 0.63 or worse (worse eye) in the presence of an amblyogenic factor; prevalence was 5%. There were three groups: participants with amblyopia (n = 78), participants with a visual acuity of 0.63 or worse (worse eye) without amblyopia (n = 65), and participants with a visual acuity of better than 0.63 (worse eye) (n = 1,426). Visuospatial planning ability was measured by the ToL test (touch-screen version), and the performance score ranged from 0 to 24, depending on the number of correctly solved problems. The authors used linear regression models to investigate the association between amblyopia and ToL test scores, adjusting for age, sex, and socioeconomic status. The mean ± standard deviation of ToL test performance was 15.31 ± 3.29 in participants with a visual acuity of better than 0.63, 14.56 ± 3.76 in the amblyopic group, and 15.14 ± 3.65 in participants with a visual acuity of 0.63 or worse without amblyopia. In a linear regression model, sex, and socioeconomic status significantly predicted planning performance (P <.0001), whereas amblyopic status did not (P = .20). Amblyopia may affect visuospatial perception, but no such relationships could be found for higher cognitive functions that strongly depend on visuospatial processing. Thus, in adulthood, individuals with amblyopia are unaffected in their visuospatial cognitive abilities, as required by the ToL test. [J Pediatr Ophthalmol Strabismus. 2019;56(6):397-401.].

Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus.

BackgroundEndothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development.Methods and ResultsIn a population‐based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35–74 years at enrollment in 2007–2012), we identified 1610 cases of incident pre–diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A1c (HbA1c) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow‐mediated dilation and digital volume plethysmography–derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate β coefficients of HbA1c levels at follow‐up and relative risks of incident (pre–)diabetes mellitus. Reactive hyperemia index was independently associated with HbA1c after multivariable adjustment for baseline HbA1c, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack‐years of smoking, non–high‐density lipoprotein/high‐density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C‐reactive protein (β=−0.020; P=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02–1.15; P=0.012) for incident pre–diabetes mellitus and 1.16 (95% CI, 1.01–1.34; P=0.041) for incident type 2 diabetes mellitus. Flow‐mediated dilation independently increased the relative risk for developing pre–diabetes mellitus by 8% (95% CI, 1.02–1.14; P=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86–1.19; P=0.92) and with HbA1c (β=−0.003; P=0.59).ConclusionsEndothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre–)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.

Posterior segment eye lesions: prevalence and associations with ocular and systemic parameters: results from the Gutenberg Health Study.

To estimate the prevalence of posterior segment eye lesions and to identify their ocular and systemic associations within the Gutenberg Health Study (GHS) in Germany. Assessment and grading of fundus images as well as physical examination and history taking were performed in the cross-sectional analysis of 15,010 subjects (aged 35-74years) using standardised procedures to determine the prevalence and associations of various posterior segment eye lesions. Fundus photographs of both eyes were available for 12,782 (85.2%; 50% female) subjects. The prevalence weighted to the region of Mainz and Mainz-Bingen in Germany was for choroidal nevi 2.4%, drusen of the optic nerve head 0.2%, tilted discs 1.5%, chorioretinal scars suggestive of toxoplasmosis 0.2%, retinitis pigmentosa 0.04% and persistent hyaloid artery 0.02%. Choroidal nevi were positively associated with a history of myocardial infarction (OR = 2.7, 95% confidence interval 1.2-6.2, p value = 0.017). Tilted discs were positively associated with increased intraocular pressure (OR = 1.09 per mm Hg (1.02-1.16), p = 0.011) and negatively associated with smoking (OR 0.4 (0.3-0.7), p = 0.0022). Participants with tilted discs had a mean spherical equivalent of - 3.6dioptres (standard deviation 4.0) compared with - 0.4dioptres (2.4) to those without. Our study is-to the best of our knowledge-the first to determine the prevalence of drusen of optic nerve head among Caucasians, to show a positive association between tilted discs and increased intraocular pressure and questions a possible link between choroidal nevi and myocardial infarction. It also showed that participants with tilted discs had a lower mean spherical equivalent than those without.

RENIN, ALDOSTERONE, THE ALDOSTERONE-TO-RENIN RATIO AND INCIDENT ARTERIAL HYPERTENSION AMONG NORMOTENSIVE SUBJECTS FROM THE POPULATION

Objective: To investigate the predictive value of directly-measured plasma renin concentration (PRC), aldosterone (PAC) and the aldosterone-to-renin ratio (ARR) for incident arterial hypertension in the population. Design and method: From the sample of 15,010 participants of the population-based Gutenberg Health Study, only normotensive subjects at baseline (n = 5,362) were included in the present analysis. Concentrations of renin and aldosterone were determined by a competitive chemiluminescence immunoassay (CLIA) using the fully-automated LIAISON® platform (DiaSorin). Extreme quartiles (Q) of biomarker concentrations were compared by means of regression analysis, adjusted for traditional CVRF, renal function and hormonal status (in women only). Results: During a follow-up period of five years, new-onset hypertension developed in 996 participants (18.6%). Among men, the relative risk (RR) for incident arterial hypertension was found to be 1.49 (95% confidence interval (CI) 1.19–1.86; p = 0.00054; Q1 vs Q4ref) for renin; 1.26 (95%CI 1.02–1.56, p = 0.029; Q4 vs Q1ref) for aldosterone and 1.70 (95%CI 1.33–2.12; p < 0.0001; Q4 vs Q1ref) for ARR in a fully adjusted model. In females, only high ARR was an independent predictor of incident arterial hypertension (RR 1.29 (95% CI 1.04–1.62); p = 0.024). In the subgroup of individuals with concentrations within the reference range, only ARR (Q4 vs Q1ref) was predictive for the new-onset hypertension in men (RR 1.44 (95%CI 1.13–1.83) p = 0.003). Synergistic effects of co-prevalent obesity and biomarker concentrations on incident hypertension were also demonstrated, resulting in a markedly higher risk estimates (e.g. men in Q4 of ARR and having BMI >= 30 kg/m2 had compared to subjects with normal weight and low ARR (Q1ref), a RR of 2.92 (95% 1.90–4.49); p < 0.0001)). Conclusions: Among normotensives from the general population ARR possesses a stronger predictive value for the development of new-onset hypertension than renin or aldosterone alone. The prediction of the development of arterial hypertension by ARR was even stronger in obese subjects.

Vision-related quality of life considering both eyes: results from the German population-based Gutenberg Health Study (GHS)

PurposeMost definitions of visual impairment focus on the status of the better-seeing eye only, but this approach might underestimate the influence of the worse-seeing eye on the vision-related quality of life (VRQoL).MethodsWe assessed distance-corrected visual acuity in both eyes and VRQoL using the “National Eye Institute 25-Item Visual Function Questionnaire” (NEI VFQ-25) in the German population-based Gutenberg Health Study. We calculated the Rasch-based visual functioning scale (VFS) and socioemotional scale (SES). We categorized the visual acuity of the better-seeing eye (BE) and worse-seeing eye (WE) as follows: (1) no visual impairment (VI) (< 0.32 logMAR)), (2) mild VI (0.32–0.5 logMAR), and (3) moderate to severe VI (> 0.5 logMAR). Next, the subjects were categorized as follows: both eyes with no VI (no/no), the better-seeing eye with no VI and the worse-seeing eye with mild VI (no/mild), no VI/severe VI (no/severe), both eyes with mild VI (mild/mild), light VI/severe VI (mild/severe), and both eyes with severe VI (severe/severe). We calculated the median scores for VFS and SES. We used linear regression to estimate the combined influence of BE/WE on VFS and SES.ResultsWe included 11,941 participants (49.9% female, age range: 35–74 years) with information on VRQoL and visual acuity. The median VFS/SES scores were 90/100 (no/no VI group), 84/97 (no/mild group), 81/94 (no/severe group), 70/90 (mild/mild group), 67/74 (mild/severe group), and 63/76 (severe/severe group). These differences were supported by the regression analysis results.ConclusionRelying on the function of the better-seeing eye considerably underestimates the impact of visual impairment on VRQoL.

Choroidal thickness is associated with cardiovascular risk factors and cardiac health: the Gutenberg Health Study.

Choroidal thickness is associated with several cardiovascular parameters in case-control studies including patients with manifest disease. So far, it was unclear whether underlying cardiovascular risk factors or the continuum of heart failure may lead to alterations of the choroid. Therefore, our hypothesis was to test in a population-based study, whether choroidal thickness is associated with cardiovascular risk factors and heart disease. A population-based cross-sectional study was carried out in Germany. A comprehensive medical examination including assessment of cardiovascular risk factors, echocardiography and ophthalmological examinations with spectral-domain optical coherence tomography of the choroid was performed. Subfoveal choroidal thickness as well as left ventricular ejection fraction (LVEF) and a surrogate marker for left ventricular end-diastolic pressure (E/e') were measured. Linear regression analyses were carried out to determine the relationship between subfoveal choroidal thickness and age, sex, body mass index, systolic blood pressure, dyslipidemia, HbA1c level, hematocrit, estimated glomerular filtration rate (eGFR), LVEF, E/e' and left ventricular mass index adjusted for ocular parameters. 1.742 subjects (48% females) with amean age 59.3 ± 10.6years were included in this study. Mean subfoveal thickness was 252 ± 77µm (right eyes) and 255 ± 77µm (left eyes). Unadjusted linear regression analysis revealed that subfoveal choroidal thickness is associated with sex, age, systolic blood pressure, hematocrit, eGFR, left ventricular end-diastolic pressure, left ventricular mass index (all p < 0.001) and dyslipidemia (p = 0.009). Adjusted linear regression only revealed age as associated parameter (p < 0.001). We did find evidence for an association between subfoveal choroidal thickness and cardiovascular risk factors which was mediated by aging.