Population-based Gutenberg Health Study Research Articles

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

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

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

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

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

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

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

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

Development and Phenotype of Heart Failure in Long-Term Survivors of Childhood Cancer: The CVSS Study.

Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group. Although prevalence of HF was significantly higher in CCSs, prevalence of different HF stages varied strongly by specific tumor history. Compared with the population, the prevalence ratio was 2.6 (95% CI, 2.4-2.8) for HF stage A and 4.6 (95% CI, 4.1-5.1) for the composite of HF stage B to D in an age- and sex-adjusted Poisson regression model. Multivariable linear regression, adjusting for tumor entities, age, sex, and cardiovascular risk factors, revealed a lower left ventricular ejection fraction in patients with history of bone tumors (β, -4.30 [95% CI, -5.70 to -2.80]), soft tissue sarcoma (β, -1.60 [95% CI, -2.90 to -0.30]), and renal tumors (β, -1.60 [95% CI, -2.80 to -0.29]) compared with the population. The same model for the diastolic marker, ratio of the peak early diastolic filling velocity/lateral mitral annular early diastolic velocity, showed an association only with cardiovascular risk factors but not with tumor entities. Conclusions The prevalence of HF stage A to D was significantly higher among long-term CCSs compared with the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with tumor entities, whereas diastolic dysfunction was associated with a higher burden of cardiovascular risk factors in CCSs.

Association of autoantibody levels with different stages of age-related macular degeneration (AMD): Results from the population-based Gutenberg Health Study (GHS)

PurposeAnti-retinal autoantibodies are assumed to be associated with age-related macular degeneration (AMD). To our knowledge, this is the first evaluation of autoantibodies in human sera of participants with different stages of AMD in a large population-based, observational cohort study in Germany.MethodsThe Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. Amongst others, non-mydriatic fundus photography (Visucam PRO NM™, Carl Zeiss Meditec AG, Jena, Germany) was performed. Fundus images of the first 5000 participants were graded based on the Rotterdam Eye Study classification. Sera of participants with AMD (n=541) and sera of age-matched participants without AMD (n=490) were analyzed by antigen-microarrays. Besides descriptive statistics, autoantibody-levels were compared by Mann-Whitney-U test and the associations of level of autoantibodies with AMD were calculated by logistic regression analysis. Likewise, possible associations of the autoantibodies and both clinical and laboratory parameters on AMD subjects were analyzed.ResultsAutoantibodies against transferrin (p<0.001) were significantly downregulated in participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only compared to Controls. Mitogen-activated protein kinase 3 (p=0.041), glutathione peroxidase 4 (p=0.048), clusterin (p=0.045), lysozyme (p=0.19), protein kinase C substrate 80K-H (p=0.02), heat shock 70 kDa protein 1A (p=0.04) and insulin (p=0.018) show a trend between Control and participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only.ConclusionsThis study contributes to a growing knowledge of autoantibodies in association with different AMD stages compared to controls in the context of a large population-based study in Germany. Especially autoantibodies against inflammatory proteins were downregulated in participants with early AMD and soft, distinct drusen (≥63 μm) or pigmentary abnormalities only.

Abstract 12399: Impact of Heart Failure and Chronic Kidney Disease on Clinical Outcome in Relation to Presence of Type-2 Diabetes Mellitus - Results From the Population-Based Gutenberg Health Study

Background: Type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD) are pathophysiologically linked and impact clinical outcome. The aim of this study was to determine the co-prevalence of T2DM, CKD and HF and to evaluate their additive prognostic significancefor all-cause mortality. Methods: Data from the population-based, prospective Gutenberg Health Study were analyzed (n=15,010). Clinical parameters were assessed during a highly standardized comprehensive 5-hour investigation at a dedicated study center. HF, T2DM and CKD were defined according to international guidelines. All-cause mortality was determined by regular checks of vital status via standardized follow-up examinations and regular alignment with registration offices. Results: In total 14,872 individuals were eligible for analysis (prevalence of T2DM: 8.6%; CKD: 29.1%; HF: 3.3%). During a median follow-up of 11.8 [interquartile range 10.3-13.2] years, 1,281 individuals died. In Cox regression analysis adjusted for age and sex, CKD and HF independently denoted an increased risk for all-cause mortality in diabetics (hazard ratio (HR) CKD 1.67 [95% confidence interval 1.33-2.09], P&lt;0.0001; HR HF 2.44 [1.86-3.20], P&lt;0.0001) and non-diabetics (HR CKD 1.22 [1.07-1.41], P=0.0042; HR HF 2.55 [2.07-3.14], P&lt;0.0001). Further adjustment for traditional cardiovascular risk factors (CVRF) marginally reduced effect estimates. When considering the interaction of CKD and HF in Cox regression analysis, adjusted for age, sex, and CVRF, CKD without HF indicated a higher risk for all-cause mortality in diabetics (HR 1.66 [1.28-2.14], P=0.00011) compared with non-diabetics (HR 1.17 [1.01-1.36], P=0.04). A similar pattern, but with higher estimates was detected for HF without CKD (HR T2DM 2.56 [1.63-4.00], P&lt;0.0001 vs. HR non-diabetics 2.13 [1.60-2.83], P&lt;0.0001), and the highest were found for the co-prevalence of CKD and HF (HR T2DM 3.69 [2.59-5.27], P&lt;0.0001 vs. HR non-diabetics 3.44 [2.54 - 4.65], P&lt;0.0001). Conclusion: CKD and HF each show an independent but different risk for all-cause mortality that is modified by the prevalence of T2DM. The co-prevalence of these diseases increases mortality, underscoring the need for a holistic treatment approach.

Determinants of mammography screening participation-a cross-sectional analysis of the German population-based Gutenberg Health Study (GHS).

We investigated the association between social inequality and participation in a mammography screening program (MSP). Since the German government offers mammography screening free of charge, any effect of social inequality on participation should be due to educational status and not due to the financial burden. The 'Gutenberg Health Study' is a cohort study in the Rhine-Main-region, Germany. A health check-up was performed, and questions about medical history, health behavior, including secondary prevention such as use of mammography, and social status are included. Two indicators of social inequality (equivalence income and educational status), an interaction term of these two, and different covariables were used to explore an association in different logistic regression models. A total of 4,681 women meeting the inclusion criteria were included. Only 6.2% never participated in the MSP. A higher income was associated with higher chances of ever participating in a mammography screening (odds ratios (OR): 1.67 per €1000; 95%CI:1.26-2.25, model 3, adjusted for age, education and an interaction term of income and education). Compared to women with a low educational status, the odds ratios for ever participating in the MSP was lower for the intermediate educational status group (OR = 0.64, 95%CI:0.45-0.91) and for the high educational status group (0.53, 95%CI:0.37-0.76). Results persisted also after controlling for relevant confounders. Despite the absence of financial barriers for participation in the MSP, socioeconomic inequalities still influence participation. It would be interesting to examine whether the educational effect is due to an informed decision.

Distribution of Pupil Size and Associated Factors: Results from the Population-Based Gutenberg Health Study.

Results 18,335 eyes of 9,559 participants aged 40 to 80 years were included in the analysis. Median pupil diameter was 4.19 mm in right eyes and 4.12 mm in left eyes. A smaller pupil was associated with older age, hyperopic refractive error, previous cataract surgery, diabetes, obesity, and ACE inhibitor intake, whereas wider pupil was associated with female gender, arterial hypertension, intake of tricyclic antidepressants, and intake of SNRI and tetracyclic antidepressants. Socioeconomic status and smoking were not associated with pupil size. Conclusion Individuals of older age, after cataract surgery, under therapy with ACE inhibitors and with diabetes have a smaller pupil. This should be taken into account when planning nonmydriatic fundus photography-based screening programs, for instance, for diabetic retinopathy.

Association of birth weight with corneal aberrations in adulthood – Results from a population-based study

PurposeLow birth weight (BW) is associated with increased corneal aberrations in childhood and alterations of corneal geometry in adulthood. Increased corneal aberrations may be a factor contributing to decreased visual function in former low BW newborns in later life. Hence, the aim of this study was to analyze the long-term effect of low BW on corneal aberrations in adulthood. MethodsIn the German population-based Gutenberg Health Study (GHS) participants (age: 40–80 years) were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). The relationship between self-reported BW and the different types of corneal aberrations was analyzed using linear regression analysis as uni- and multivariable analysis with adjustment for potential confounders. The main outcome measures were corneal aberrations defined as astigmatism (Z2−2; Z22), coma (Z3−1; Z31), trefoil (Z3−3; Z33), spherical aberration (Z40) and root-mean square of higher order aberrations (HOA; 3rd up to 8th order; aperture size: 6 mm). ResultsOverall, 5,628 participants were included in this analysis (3,004 women, aged 56.0 +/- 10.3 years). In a multivariable analysis lower BW was associated with decreased horizontal trefoil (B = 0.004 [0.001; 0.006] µm/500 g; p=.008); higher spherical aberrations (B=-0.006 [-0.008;-0.003] µm/500 g; p<.001), higher RMS (B=-0.028 [-0.042;-0.014] µm/500 g; p<.001), increased HOA (B=-0.007 [-0.010;-0.003] µm/500 g; p<.001) and increased LOA (B=-0.027 [-0.041;-0.013] µm/500 g; p<.001). No association was observed between birth weight and the other types of corneal aberrations in multivariable model. ConclusionOur results indicate an association between BW and spherical aberration in adults aged 40 to 80 years. This indicates that low BW may have an association with an altered corneal shape development which may affect optical image quality and, hence, visual function.

Relationships between coagulation factors and thrombin generation in a general population with arterial and venous disease background.

BackgroundThe current study aims to identify the relationships between coagulation factors and plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals.MethodsThis study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference group) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted.ResultsThe lag time, the time to form the first thrombin, was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference group, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. Endogenous thrombin potential, or area under the curve, was predominantly positively determined by factor II, VIII, X and IX in all groups. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous disease groups in comparison to the reference group.ConclusionThis large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12959-022-00392-0.

Renin, aldosterone, the aldosterone-to-renin ratio, and incident hypertension among normotensive subjects from the general population.

To investigate the predictive ability of direct plasma renin and aldosterone concentrations as well as their ratio [aldosterone-to-renin (ARR)] for incident hypertension in the general population. Concentration of renin and aldosterone were measured by a chemiluminescence immunoassay using the fully automated LIAISON® platform (DiaSorin) among 5362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically overt cardiovascular disease at baseline. During a follow-up period of 5 years, 18.6% (n = 996) developed a new-onset hypertension. Comparing extreme quartiles of biomarker distribution, the relative risk (RR) for incident arterial hypertension was found to be 1.58 [95% confidence interval (CI) 1.25-2.00; P = 0.00015; Q1 vs. Q4ref] for renin; 1.29 (95% CI 1.05-1.59, P = 0.018; Q4 vs. Q1ref) for aldosterone and 1.70 (95% CI 1.33-2.12; P < 0.0001; Q4 vs. Q1ref) for ARR after multivariable adjustment in men. In females, only high ARR was independently predictive for incident hypertension over 5 years [RR 1.29 (95% CI 1.04-1.62); P = 0.024]. Even in the subgroup of individuals having biomarker concentrations within the reference range, high ARR was predictive for new-onset hypertension in men [RR 1.44 (95% CI 1.13-1.83); P = 0.003]. Finally, synergistic effects of co-prevalent obesity and ARR on incident hypertension were also demonstrated, resulting in markedly higher risk estimates as seen for biomarker alone [RR of 2.70 (95% CI 2.05-3.6) for Q4 of ARR and having body mass index ≥ 30 kg/m2 vs. low ARR (Q1ref) and normal weight; P < 0.0001]. Among normotensives from the general population ARR possesses a stronger predictive value for incident hypertension than renin or aldosterone alone. The prediction of arterial hypertension by ARR was even stronger in obese subjects.

Long working hours and risk of cardiovascular outcomes and diabetes type II: five-year follow-up of the Gutenberg Health Study (GHS)

ObjectivesThe aims of this study were to determine if there was an increased risk of incident cardiovascular disease (CVD) and diabetes and an increase in arterial stiffness in participants who reported working 41–54 h per week and more than 55 h compared to those who worked 40 h or less over a time interval of 5 years.MethodsIn a subsample of the population-based prospective Gutenberg Health Study (GHS) study, we examined working participants younger than 65 years at baseline (n = 7241) and after 5 years. To test the association of working time at baseline and incident cardiovascular events and diabetes type II, we estimated hazard ratios (HR) using competing risks models. For a change in the arterial stiffness index (SI) based on assessment using a Pulse Trace PCA2 device, we used multivariate linear regression models.ResultsThe SI increased in those working more than 55 h per week (beta coefficiant = 0.32 m/s (95% CI 0.07–0.58) compared to those working 40 h and less after adjustment for sex, age and SES. Due to small numbers there was no significant association of working hours and clinically manifest cardiovascular events and diabetes type II in the 5-year follow-up time.ConclusionsFurther studies are needed to confirm the results on working hours and arterial stiffness. Analyses of the 10-year follow-up with more events may clarify the results for incident cardiovascular events and metabolic outcomes.

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study.

PurposeLow birth weight (BW) is associated with alterations of foveal shape development in childhood—leading to an increased retinal thickness of the fovea. The aim of the present study was to assess whether BW has a long-term effect on foveal retinal thickness (RT) and is still present in adulthood.MethodsIn the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography. The association between self-reported BW and RT in the foveolar and perifoveal locations was assessed. Multivariable linear regression analyses with adjustment for potential confounders and grading of foveal hypoplasia were performed.ResultsOverall, RT measurements and self-reported BW were available for 2,539 participants (1300 female, mean age 54.5 ± 9.7 years). The absolute foveolar RT was 239.6 ± 25.8 µm, 232.2 ± 20.1 µm and 234.8 ± 21.0 µm, respectively, in the low (<2500 g), normal (2500–4000 g) and high (>4000 g) BW groups (P < 0.001). After adjustment for confounders, an association was observed between lower BW and increased foveolar thickness (B = –0.35 [95% confidence interval {CI}: –0.49; –0.20] µm/100 g; P < 0.001), whereas only a weak association with RT was observed with the nasal (P = 0.010), temporal (P = 0.011), and inferior (P = 0.021) quadrants in the 1 mm distance, with no association in the 2 mm distance to the fovea. Foveal hypoplasia grade 1 was more frequent in the low BW group (6.8%) compared to the normal (0.9%) and high BW group (1.2%).ConclusionsThis study provides evidence of an association between lower BW and increased foveolar thickness and foveal hypoplasia, indicating that prenatal growth may affect macular morphology, which in turn may persist until adulthood and predispose to retinal disease later in life.

Disturbed Glucose Metabolism and Left Ventricular Geometry in the General Population.

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH). Methods: 15,010 subjects (35–74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up. Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) over prediabetes (17.8%) to T2DM (23.8%). Prediabetes and T2DM were associated with increased LV mass index (prediabetes: β1.3 (95% CI 0.78–1.81), p < 0.0001; T2DM: β2.37 (95% CI 1.81; 2.92), p < 0.0001) independent of age, sex, and cardiovascular risk factors (CVRF). The frequency of LVH was related to the presence of T2DM (prevalence ratio (PR)T2DM 1.2 (95% CI 1.06–1.35), p = 0.0038). T2DM was related to mortality independent of age, sex, and CVRF regardless of LVH (hazard ratio (HR)T2DM-LVH 2.67 (95% CI 1.94–3.66), p < 0.0001; HRT2DM-noLVH 1.59 (95% CI 1.29–1.96), p < 0.0001), prediabetes was only associated with outcome in individuals with LVH independent of age and sex (HRprediabetes-LVH 1.51 (95% CI 1.01–2.25), p = 0.045). Neither T2DM nor prediabetes were predictors of incident LVH after adjustment for clinical covariates. Conclusions: Prediabetes and T2DM promote alterations of cardiac geometry. T2DM and particularly the coprevalence of T2DM with LVH substantially reduce life expectancy. These findings highlight the need for new therapeutic and screening approaches to prevent and detect cardiometabolic diseases at an early stage.

Obstructive sleep apnea predicts 10-year cardiovascular disease-related mortality in the Sleep Heart Health Study: a machine learning approach.

Obstructive sleep apnea (OSA) is considered to be an important risk factor for the development of cardiovascular disease (CVD). This study aimed to develop and evaluate a machine learning approach with a set of features for assessing the 10-year CVD mortality risk of the OSA population. This study included 2,464 patients with OSA who met study inclusion criteria and were selected from the Sleep Heart Health Study. We evaluated the importance of potential features by mutual information. The top 9 features were selected to develop a random forest model. We evaluated the model performance on a test set (n = 493) using the area under the receiver operating curve with 95% confidence interval and confusion matrix. A random forest model awarded the highest area under the receiver operating curve of 0.84 (95% confidence interval: 0.78-0.89). The specificity and sensitivity were 73.94% and 81.82%, respectively. Sixty-three years old was a threshold for increased risk of 10-year CVD mortality. Persons with severe OSA had higher risk than those with mild OSA. This study demonstrated that a random forest model can provide a quick assessment of the risk of 10-year CVD mortality. Our model may be more informative for patients with OSA in determining their future CVD mortality risk. Li A, Roveda JM, Powers LS, Quan SF. Obstructive sleep apnea predicts 10-year cardiovascular disease-related mortality in the Sleep Heart Health Study: a machine learning approach. J Clin Sleep Med. 2022;18(2):497-504.

Five-year cumulative incidence and progression of age-related macular degeneration: results from the German population-based Gutenberg Health Study (GHS)

PurposeAge-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort.MethodsThe Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age. The baseline examination, including fundus photography, was conducted between 2007 and 2012, and the 5-year follow-up examination was performed between 2012 and 2017. AMD grading of fundus photographs was performed according to the Rotterdam Eye Study classification. The 5-year cumulative incidence and progression of AMD were calculated. Poisson regression analysis was conducted to investigate factors associated with the cumulative incidence and progression of AMD.ResultsSix-thousand-eight-hundred-eighty-eight participants (49.8%, n = 3427 female) were included in the analysis. AMD prevalence was 8.5% [95% CI: 7.9–9.2%] at baseline and 10.3% [95% CI: 9.6–11.1%] at follow-up. The cumulative 5-year-incidence was 2.0% [1.7–2.4%]. AMD progression within 5 years was seen in 18.1% [95% CI: 15.1–21.5%] of the participants. AMD incidence and AMD progression were associated with higher age, for each 10-year increase in age, the risk of AMD doubles (RR = 2.30), and the risk of progression of the disease is increased by 1.6. while AMD incidence also with pseudophakic status.ConclusionsIn summary, this population-based sample provides substantial epidemiologic data from a large German cohort, including data on progression and cumulative incidence of macular degeneration in younger age groups. AMD progression over 5 years is common in the German population, 18.1% of subjects with AMD showed progression in at least one eye in this time frame and is associated with higher age. Nevertheless, although usually defined to occur over the age of 50, in this cohort AMD occurred in 0.5% and AMD progression occurred in 5.4% of those already affected in the youngest age group before 50 years of age.

Refined atrial fibrillation screening and cost-effectiveness in the German population

ObjectiveLittle is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.MethodsWe performed a...

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

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

Tubulin-folding cofactor E deficiency promotes vascular dysfunction by increased endoplasmic reticulum stress.

AimsAssessment of endothelial function in humans by measuring flow-mediated dilation (FMD) risk-stratifies individuals with established cardiovascular disease, whereas its predictive value is limited in primary prevention. We therefore aimed to establish and evaluate novel markers of FMD at the population level.Methods and resultsIn order to identify novel targets that were negatively correlated with FMD and investigate their contribution to vascular function, we performed a genome-wide association study (GWAS) of 4175 participants of the population based Gutenberg Health Study. Subsequently, conditional knockout mouse models deleting the gene of interest were generated and characterized. GWAS analysis revealed that single-nucleotide polymorphisms (SNPs) in the tubulin-folding cofactor E (TBCE) gene were negatively correlated with endothelial function and TBCE expression. Vascular smooth muscle cell (VSMC)-targeted TBCE deficiency was associated with endothelial dysfunction, aortic wall hypertrophy, and endoplasmic reticulum (ER) stress-mediated VSMC hyperproliferation in mice, paralleled by calnexin up-regulation and exacerbated by the blood pressure hormone angiotensin II. Treating SMMHC-ERT2-Cre+/−TBCEfl/fl mice with the ER stress modulator tauroursodeoxycholic acid amplified Raptor/Beclin-1-dependent autophagy and reversed vascular dysfunction.ConclusionTBCE and tubulin homeostasis seem to be novel predictors of vascular function and offer a new drug target to ameliorate ER stress-dependent vascular dysfunction.