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Abstract Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.

Abstract 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

Abstract Previous studies on self-rated health and mortality have usually not differentiated between physical and mental health, respectively have not considered physical diseases. This study aims to determine self-rated physical and mental health from middle to old age, examine associations with mortality adjusted for objective risk factors and assess effect modification by gender. In a large population-based sample (N = 14,993 at baseline), self-rated physical and mental health were rated separately by a single-item. Associations to mortality were modelled by Cox regressions, adjusting for potential confounding variables. Most participants rated their physical (79.4%), resp. mental health (82.3%) as good. Poor self-rated physical health was lowest in the youngest group (19.6%, age 35–44), and highest in midlife (29.1%, age 55–64). Poor self-rated mental health was lowest among the oldest (18.5%), and highest from 45 to 54 years (29.3%). Poor self-rated physical, but not mental health was predictive of mortality when adjusting for objective risk factors. Male gender and poor self-rated physical health interacted (RERI 0.43 95%-CI 0.02–0.85). Self-rated physical health was best in the youngest and worst in the midlife group, this pattern was reversed regarding self-rated mental health. Poor self-rated physical, but not mental health was predictive of mortality, adjusting for objective risk factors. It was more strongly predictive of mortality in men than in women. Poor subjective physical health ratings, should be taken seriously as an unfavorable prognostic sign, particularly in men.

Abstract Animal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.

Abstract Feasibility and efficacy of complex percutaneous coronary intervention (PCI) in the elderly, a more frail population due to more comorbidities is incompletely understood. We therefore set out to compare success and complication rate of PCI for chronic total occlusion (CTO) in octogenarians, in comparison to non-octogenarians. Data from 267 patients (58 patients over 80 years of age and 209 under 80 years of age) who had undergone CTO PCI were analyzed. To compare the results we calculated the propensity score and used inverse probability of treatment weighting. We evaluated demographic, clinical, angiographic, and periprocedural information. The median age of the total collective was 68 (31–90) years (octogenarian collective 82 (80–90) years vs non-octogenarians 65 (31–79) years). We observed a high success rate in both collectives (82.8% vs 90.4%, p = 0.10) and no difference in periprocedural complications or complications in the follow-up period. In our collective restenosis rate at follow-up was comparable to the propensity sore weighted population (11.3% vs 16.3%, p = 0.9). Our results show that CTO PCI in older patients is safe and feasible with comparable in-hospital and follow-up complication rates compared to a younger patient population.

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

Abstract Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35–74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β − 0.36, 95% CI − 0.63/− 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β − 0.34, 95% CI − 0.53/− 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β − 0.656, 95% CI − 1.07/− 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HRperSD) 1.60, 95% CI 1.39–1.85; P

Abstract Environmental stress like important soccer events can induce excitation, stress and anger. We aimed to investigate (i) whether the FIFA soccer world cup (WC) 2014 and (ii) whether the soccer games of the German national team had an impact on total numbers and in-hospital mortality of patients with myocardial infarction (MI) in Germany. We analyzed data of MI inpatients of the German nationwide inpatient sample (2013–2015). Patients admitted due to MI during FIFA WC 2014 (12th June–13th July2014) were compared to those during the same period 2013 and 2015 (12th June–13th July). Total number of MI patients was higher during WC 2014 than in the comparison-period 2013 (18,479 vs.18,089, P

Abstract Glomerular filtration rate (GFR) declines with age by approx. 1 ml/min/m2 per year beginning in the third decade of life. At 70 years of age > 40 ml/min/m2 of GFR will be lost. Thus, factors affecting loss of GFR have significant public health implications. Furthermore, the definition of chronic kidney disease based on GFR may not be appropriate for the elderly. We analyzed factors affecting absolute and relative change of eGFR over a 5 year period in 12,381 participants of the Gutenberg Health Study. We estimated GFR at baseline and after 5 years of follow-up by two different equations. Association with the decline of estimated GFR (eGFR) was assessed by multivariable regression analysis. We confirmed a median loss of eGFR per year of approx. 1 ml/min/m2. Aside from albuminuria systolic blood pressure was most strongly associated with faster decline of eGFR followed by echocardiographic evidence of left ventricular diastolic dysfunction and reduced ejection fraction. White blood cell count showed a moderate association with eGFR loss. Diastolic blood pressure, serum uric acid and serum albumin were associated with slower GFR decline in multivariable analysis. Sensitivity analysis with exclusion of individuals taking diuretics, antihypertensive, antidiabetic, or lipid lowering drugs confirmed these associations.

Abstract To evaluate the cost-saving of a specialized, eHealth-based management service (CS) in comparison to regular medical care (RMC) for the management of patients receiving oral anticoagulation (OAC) therapy. Costs of hospitalization were derived via diagnosis-related groups which comprise diagnoses (ICD-10) and operation and procedure classification system (OPS), which resulted in OAC-related (i.e. bleeding/ thromboembolic events) and non-OAC-related costs for both cohorts. Cost for anticoagulation management comprised INR-testing, personnel, and technical support. In total, 705 patients were managed by CS and 1490 patients received RMC. The number of hospital stays was significantly lower in the CS cohort compared to RMC (CS: 23.4/100 py; RMC: 68.7/100 py); with the most pronounced difference in OAC-related admissions (CS: 2.8/100 py; RMC: 13.3/100 py). Total costs for anticoagulation management amounted to 101 EUR/py in RMC and 311 EUR/py in CS, whereas hospitalization costs were 3261 [IQR 2857–3689] EUR/py in RMC and 683 [504–874] EUR/py in CS. This resulted in an overall cost saving 2368 EUR/py favoring the CS. The lower frequency of adverse events in anticoagulated patients managed by the telemedicine-based CS compared to RMC translated into a substantial cost-saving, despite higher costs for the specialized management of patients. Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.

Abstract Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.

Abstract Patients undergoing knee joint replacement (KJR) are at high risk of postoperative venous thromboembolism (VTE), but data on the time trends of VTE rate in this population are sparse. In this analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary KJR in Germany 2005–2016. Overall, 1,804,496 hospitalized patients with elective primary KJR (65.1% women, 70.0 years [IQR 63.0–76.0]) were included in the analysis. During hospitalization, VTE was documented in 23,297 (1.3%) patients. Total numbers of primary KJR increased from 129,832 in 2005 to 167,881 in 2016 (β-(slope)-estimate 1,978 [95% CI 1,951 to 2,004], P

Abstract 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.

Abstract Previous reports have investigated the impact of age on D-Dimer testing in elderly individuals with suspected deep vein thrombosis (DVT), but data on the age-related diagnostic value of D-dimer in a sample covering a broad age range are limited. The present study determined age-specifically the diagnostic accuracy of D-dimer and compared it to C-reactive protein (CRP), a marker of inflammation, in 500 patients with suspected DVT from the VTEval project (NCT02156401). Sensitivity of D-dimer was lower in patients 0.05). In conclusion, these data outline a clinically-relevant limitation of D-dimer testing among younger patients with suspected DVT indicating a necessity for age-adapted cut-off values. Further research is required to decrypt the role of inflammation in the pathophysiology and diagnosis of venous thrombosis.

Abstract The relation between inflammation, hemostasis and arterial stiffness is of pathophysiological relevance for the development of cardiovascular disease (CVD). Data investigating this interplay using stiffness index (SI) by digital photoplethysmography are not available yet. Therefore, sex-specific relation between SI and inflammatory and hemostatic biomarkers was investigated within 13,724 subjects from the population-based Gutenberg Health Study. C-reactive protein (CRP), white blood cell count (WBCC), neopterin, interleukin-18, interleukin-1 receptor antagonist (IL-1RA), fibrinogen and hematocrit were measured. Multivariable linear regression analysis with adjustment for cardiovascular risk factors, medication, and hormonal status (in females) revealed an independent association between SI and WBCC, IL-1RA and hematocrit in both sexes, and with fibrinogen in women. There was a joint effect of increasing tertiles of SI and biomarker concentrations for future CVD risk prediction. Subjects with both SI and biomarker concentration above the median had the worst overall survival and with both below the median the best survival during a follow-up period of 6.2 ± 1.7 years, except for hematocrit. The results support the relation between inflammation, hemostasis and arterial stiffness measured by digital photoplethysmography. Markers of inflammation and hemostasis modulate the ability of SI to identify subjects at risk for future CVD or higher mortality.