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1.
Eur J Public Health ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32034913

RESUMO

BACKGROUND: 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. METHODS: We investigated longitudinal data of N = 11 905 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. RESULTS: 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). CONCLUSIONS: 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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31922545

RESUMO

AIMS: Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown. METHODS AND RESULTS: We analyzed data from the multi-center cohort study thrombEVAL (NCT01809015), investigating the efficacy of OAC with vitamin K-antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1,558 participants, information about depressive symptoms, as measured by the two-item screener PHQ-2, was available in n = 1,405 individuals. The mean follow-up period was 28.04 months, with a standard deviation of 11.52 months. In multivariable Cox regression analysis, baseline PHQ-2 sum score was a strong and robust predictor of clinically-relevant bleeding (hazard ratio (HR) 1.13, 95% confidence interval 1.03-1.24; p = 0.011) and all-cause mortality (HR 1.18, 1.08-1.28; p = 0.001) independent of age, sex, high school graduation, partnership, clinical profile, intake of SSRI, and quality of OAC therapy. Individuals with clinically significant depressive symptoms (PHQ-2 ≥3) had a 57% increased risk for clinically relevant bleeding (fully adjusted HR 1.57, 1.08-2.28) and 54% greater risk for death (fully adjusted HR 1.54, 1.09-2.17). There was no association of depressive symptoms with thromboembolic events. For hospitalization, individuals with depressive symptoms (PHQ-2 ≥3) did not experience an elevated risk in the fully adjusted model (HR 1.08, 0.86, 1.35; p = 0.52). CONCLUSIONS: Assessment of depression by the PHQ-2 provided independent long-term prognostic information beyond common biomedical risk factors. These findings highlight the need for targeting depressive symptoms in the management of patients receiving OAC therapy.

3.
Clin Res Cardiol ; 109(2): 172-182, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31168641

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 1.742 subjects (48% females) with a mean age 59.3 ± 10.6 years were included in this study. Mean subfoveal thickness was 252 ± 77 µm (right eyes) and 255 ± 77 µm (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). CONCLUSIONS: We did find evidence for an association between subfoveal choroidal thickness and cardiovascular risk factors which was mediated by aging.

4.
Eur Heart J ; 41(4): 509-518, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31120118

RESUMO

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

5.
Haematologica ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806688

RESUMO

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. This study aims to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, N=5000 subjects from the population-based Gutenberg Health Study were analysed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factors trigger 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% CI: 1.07; 2.00], p=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio = 1.50, [1.06; 2.13], p=0.023) above the 95th percentile of the reference group, independent of the cardiovascular risk profile. This large-scale study demonstrates traditional cardiovascular risk factors, particularly obesity, as relevant determinants of thrombin generation. Lag time and endogenous thrombin potential were found as potentially relevant predictors of increased total mortality, which deserves further investigation.

6.
Sci Rep ; 9(1): 18929, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831794

RESUMO

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.

7.
Br J Ophthalmol ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31843792

RESUMO

AIMS: To determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors. DESIGN: The Gutenberg Health Study is a population-based study, including 15 010 participants aged 35-74 years. METHODS: Myopic maculopathy was graded in phakic eyes with spherical equivalent ≤-6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associated factors with myopic maculopathy. RESULTS: Myopic maculopathy was present in 10.3% (95% CI 7.9 to 13.3) study participants. The prevalence was 8.6% (95% CI 6.1% to 11.9%) in the 397 right eyes and 8.7% (95% CI 6.2% to 12.0%) in the 404 left eyes. The most common type of pathology was diffuse atrophy (8.1%), followed by patchy atrophy (1.3%) and macular atrophy (0.5%); plus lesions were present in 3% (right eyes). Age (OR 1.07 per year, 95% CI 1.03 to 1.11, p<0.001), higher myopic refractive error (p<0.001), and male gender (p=0.02) were associated with myopic maculopathy, while cardiovascular risk factors and socioeconomic factors were not. CONCLUSIONS: The prevalence of myopic maculopathy in the German population was 0.5%, and 10% in high myopic participants, aged 35-74 years. These population-based data are the first in Europe. Myopic maculopathy was related to severity of myopic refractive error and age.

8.
Sci Rep ; 9(1): 20090, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882836

RESUMO

Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: -6.85, 95% confidence interval: -12.19,-1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

9.
Acta Ophthalmol ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680456

RESUMO

PURPOSE: We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. METHODS: 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. RESULTS: A total of 1890 people aged 40-80 years 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. CONCLUSIONS: Epiretinal membranes are more frequent in older and myopic subjects and in those with prior retinal laser therapy.

10.
PLoS One ; 14(11): e0224608, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682633

RESUMO

PURPOSE AND METHODS: A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20-84 years). RESULTS: Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (ß = -0.07; 95%CI -0.10, -0.04) than in women (ß = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51). CONCLUSIONS: Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.

11.
Hepatol Commun ; 3(11): 1472-1481, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31701071

RESUMO

Cardiovascular disease (CVD) is the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The current analysis expands the knowledge on atherogenic lipid profiles in NAFLD by modeling changes in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) in a prospectively enrolling real-life study cohort to inform physicians on the cardiovascular (CV) event risk based on these changes. A total of 304 patients with histologically confirmed NAFLD were included (mean age, 52 years; equal sex distribution). Of these, 129 (42.4%) patients exhibited a NAFLD activity score ≥4 and 186 (61.2%) had at least intermediate fibrosis ≥F2. The median TC levels were 209 mg/dL (interquartile range [IQR], 183, 239), LDL-C 131 mg/dL (IQR, 103, 152), and high-density lipoprotein cholesterol (HDL-C) 45 mg/dL (IQR, 38, 52). Only 16.9% of patients received lipid-lowering therapy. According to the LDL/HDL ratio, 69 (23.7%) patients exhibited a high CV risk. The 10-year CV event risk according to the Framingham risk score (FRS) was low in 91 (41.2%), intermediate in 59 (26.7%), and high in 71 (32.1%) patients and higher in the ≥F2 NAFLD population. A moderate increase in LDL-C levels by 20 mg/dL led to a transition of 20% of patients into the high-risk group when assessing the LDL/HDL ratio. According to the FRS, 6 (2.7%) patients moved from low to intermediate and 11 (4.9%) from intermediate to high CV risk. Conclusion: Patients with NAFLD exhibit a substantial CV event risk and are frequently undertreated with lipid-lowering medication. Moderate increases in LDL-C would result in worsening of the CV event risk in approximately 7.8% of all patients without a history of CVD.

12.
Ocul Surf ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31734512

RESUMO

PURPOSE: To 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. METHODS: The 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. RESULTS: The length of wetting of the Schirmer strips for ST-5 was 23.2 ±â€¯9.31 mm for right and 22.9 ±â€¯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. CONCLUSIONS: For 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.

13.
Psychooncology ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713915

RESUMO

OBJECTIVE: Long-term childhood cancer survivors (CCS) are less likely to become parents than their peers of the same age. Previous research has suggested that besides fertility, this outcome is shaped by psychosocial factors such as emotional motives toward having a child. Drawing from a sample of CCS with survival times >25 years, we present the validation of a questionnaire assessing cancer-specific reproductive motives and concerns. METHODS: We evaluated the cancer-specific version of the Leipzig Questionnaire of Motives to have a Child (LKM-C) in a register-based sample of adult CCS (N = 632, 31% had children, 44.5% women). We conducted a confirmatory factor analysis and tested associations with sociodemographic characteristics and psychological symptoms (PHQ-9, GAD-2). RESULTS: The questionnaire showed good item discrimination parameters and reliability (α = 0.86). The two-factorial structure was confirmed with the independent scales "return to normalcy" and "illness-related worries (child's/own health)." On average, CCS reported more motives in favor of a child than worries (P < .001; d = 1.12). Favorable attitudes were associated with the presence of a partnership and children, stronger current desire for a child, and fewer depressive symptoms. Worries were associated with an unfulfilled desire to have a child and elevated levels of depression and anxiety symptoms. CONCLUSIONS: The LKM-C offers a brief measure of parenthood motivations in long-term CCS. Having a child signifies return to normalcy, health, fulfillment of life perspectives, and enrichment of the partnership. Less intense worries included illnesses of the child and concerns regarding one's own health. The questionnaire could inform follow-up care, psychotherapy, and fertility treatments.

14.
J Pediatr Ophthalmol Strabismus ; 56(6): 397-401, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743409

RESUMO

PURPOSE: To determine whether amblyopia interferes with cognitive functions requiring visuospatial processing, measured by the Tower of London (ToL) test. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.].

15.
Invest Ophthalmol Vis Sci ; 60(14): 4943-4950, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770434

RESUMO

Purpose: This study analyzed whether low birth weight is linked to prevalence and incidence of age-related maculopathy (AMD) in adulthood. Methods: 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. Results: 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. Conclusions: 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.


Assuntos
Recém-Nascido de Baixo Peso , Degeneração Macular/epidemiologia , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fotografação , Prevalência , Fatores de Risco
16.
Basic Res Cardiol ; 114(6): 46, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664594

RESUMO

Nocturnal train noise exposure has been associated with hypertension and myocardial infarction. It remains unclear whether acute nighttime train exposure may induce subclinical atherosclerosis, such as endothelial dysfunction and other functional and/or biochemical changes. Thus, we aimed to expose healthy subjects to nocturnal train noise and to assess endothelial function, changes in plasma protein levels and clinical parameters. In a randomized crossover study, we exposed 70 healthy volunteers to either background or two different simulated train noise scenarios in their homes during three nights. After each night, participants visited the study center for measurement of vascular function and assessment of other biomedical and biochemical parameters. The three nighttime noise scenarios were exposure to either background noise (control), 30 or 60 train noise events (Noise30 or Noise60), with average sound pressure levels of 33, 52 and 54 dB(A), respectively. Flow-mediated dilation (FMD) of the brachial artery was 11.23 ± 4.68% for control, compared to 8.71 ± 3.83% for Noise30 and 8.47 ± 3.73% for Noise60 (p < 0.001 vs. control). Sleep quality was impaired after both Noise30 and Noise60 nights (p < 0.001 vs. control). Targeted proteomic analysis showed substantial changes of plasma proteins after the Noise60 night, mainly centered on redox, pro-thrombotic and proinflammatory pathways. Exposure to simulated nocturnal train noise impaired endothelial function. The proteomic changes point toward a proinflammatory and pro-thrombotic phenotype in response to nocturnal train noise and provide a molecular basis to explain the increased cardiovascular risk observed in epidemiological noise studies.

17.
JCI Insight ; 4(23)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31600170

RESUMO

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

18.
J Am Heart Assoc ; 8(20): e012509, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31583936

RESUMO

Background Endothelial 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 Results In 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 ß 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 (ß=-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 (ß=-0.003; P=0.59). Conclusions Endothelial 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.

19.
PLoS Med ; 16(9): e1002903, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31553733

RESUMO

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

20.
J Psychosom Res ; 124: 109760, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31443804

RESUMO

OBJECTIVE: In aging populations, a growing number of individuals are affected by cancer. However, the relevance of the disease for mental health is still controversial, especially after treatment. We drew from a representative community sample to explore the link of cancer with mental health assessing different dimensions and different periods of time. METHODS: A cohort of 14,375 men and women (35-74 years) underwent medical assessments and was queried about cancer history, previous diagnoses of mental disorders, current mental distress symptoms, and current subjective health appraisal. RESULTS: 1066 participants (7.4%) reported a diagnosis of cancer (survival time M = 9.79 (SD = 9.07) years). Most common were breast (24.3%), skin (20.9%), gynecological (13.8%), and prostate cancer (12.9%). Based on cut-off-scores of standardized self-report scales (PHQ-9, GAD-2), rates of depression (8.4%; 95%CI 6.90-10.30) and anxiety symptoms (7.8%; 95%CI 6.30-9.60) corresponded to those of participants without cancer. In men, cancer was related to a lifetime diagnosis of depression (OR = 2.15; 95%CI 1.25-3.64). At the time of assessment, cancer was associated with reduced subjective health in both sexes and with anxiety symptoms in men (OR = 2.43; 95%CI 1.13-4.98). CONCLUSION: Findings indicate different relations of cancer in men and in women with different operationalizations of mental health. They underscore that a history of cancer is not universally linked to distress in the general population. The study points out that different ascertainments of the association of cancer and mental health might be traced back to different assessment strategies. It also notes potential targets for interventions to alleviate distress, e.g. by physical activity.

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