Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

Increase in Mental Disorders During the COVID-19 Pandemic-The Role of Occupational and Financial Strains.

BACKGROUND: Numerous studies have reported an increase in mental disorders during the COVID-19 pandemic, but the exact reasons for this development are not well understood. In this study we investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. METHODS: We analyzed data from the German National Cohort (NAKO) Study. Between May and November 2020, 161 849 study participants answered questions on their mental state and social circumstances. Their responses were compared with data from the baseline survey before the pandemic (2014-2019). Linear fixed-effects models were used to determine whether individual changes in the severity of symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/ financial changes (controlling for various covariates). RESULTS: The prevalence of moderate or severe symptoms of depression and anxiety increased by 2.4% and 1.5%, respectively, during the COVID-19 pandemic compared with the preceding years. The mean severity of the symptoms rose slightly. A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91; 1.41], range 0-27). Increases were also seen for reduced working hours with no short-time allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. CONCLUSION: Depressive symptoms and anxiety disorders increased slightly in the study population during the first year of the COVID-19 pandemic. Occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures.

Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

The Impact of the COVID-19 Pandemic on Self-Reported Health.

BACKGROUND: The pandemic caused by the coronavirus SARS-CoV-2 and the countermeasures taken to protect the public are having a substantial effect on the health of the population. In Germany, nationwide protective measures to halt the spread of the virus were implemented in mid-March for 6 weeks. METHODS: In May, the impact of the pandemic was assessed in the German National Cohort (NAKO). A total of 113 928 men and women aged 20 to 74 years at the time of the baseline examination conducted 1 to 5 years earlier (53%) answered, within a 30-day period, a follow-up questionnaire on SARS-CoV-2 test status, COVID-19- associated symptoms, and self-perceived health status. RESULTS: The self-reported SARS-CoV-2 test frequency among the probands was 4.6%, and 344 participants (0.3%) reported a positive test result. Depressive and anxiety-related symptoms increased relative to baseline only in participants under 60 years of age, particularly in young women. The rate of moderate to severe depressive symptoms increased from 6.4% to 8.8%. Perceived stress increased in all age groups and both sexes, especially in the young. The scores for mental state and self-rated health worsened in participants tested for SARS-CoV-2 compared with those who were not tested. In 32% of the participants, however, self-rated health improved. CONCLUSION: The COVID-19 pandemic and the protective measures during the first wave had effects on mental health and on self-rated general health.

The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality-Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002-2016.

AIMS: Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers. METHODS: We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002-2006) and first follow-up (2007-2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders. RESULTS: Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6-2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5-6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1-16.8 per each doubling of follow up sTNF-R1 value). CONCLUSION: Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

[The investigation of health outcomes in the German National Cohort: the most relevant endpoints and their assessment]. / Erforschung von Erkrankungen in der NAKO Gesundheitsstudie. Die wichtigsten gesundheitlichen Endpunkte und ihre Erfassung.

The focus of the German National Cohort, the largest population-based cohort study in Germany to date, is the investigation of the most important widespread diseases, such as cardiovascular diseases, diabetes, cancer, neurological and psychiatric disorders, and frequent respiratory and infectious diseases. This cohort will answer questions on the development of these diseases and on the impact of genetic, environmental and lifestyle-related risk factors. Another focus is on the identification of early, subclinical markers of emerging diseases. To answer these questions, a comprehensive assessment of these health outcomes as well as of all potential determinants and precursors is mandatory.This paper describes the various health outcomes that are assessed in the German National Cohort, as well as the examination modules that are applied for deep phenotyping of study participants. Repeated collection of biosamples as well as functional measurements and application of modern imaging techniques at various time points allow for assessing the dynamics of physiological changes related to the individuals' health status. The prognostic value of these changes for disease development will be explored and translated to novel approaches for prevention and personalised medicine. Incident diseases are being assessed through self-reports by study participants and through record linkage with data from health insurances and cancer registries. Additional information about clinical diagnoses is obtained from the treating physicians to ensure the highest possible validity.

[The baseline assessment of the German National Cohort (NAKO Gesundheitsstudie): participation in the examination modules, quality assurance, and the use of secondary data]. / Die Basiserhebung der NAKO Gesundheitsstudie: Teilnahme an den Untersuchungsmodulen, Qualitätssicherung und Nutzung von Sekundärdaten.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.

Changes in fat mass and fat-free-mass are associated with incident hypertension in four population-based studies from Germany.

BACKGROUND: We estimated the association of changes in body weight, waist circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood pressure and incident hypertension using data from four German population-based studies. METHODS: We analyzed data from 4467 participants, aged 21 to 82 years not taking antihypertensive medication and not having type 2 diabetes mellitus or a history of myocardial infarction at baseline and follow-up, from four population-based studies conducted in Germany. Body weight, WC, and blood pressure were measured at baseline and follow-up (median follow-up of the single studies 4 to 7 years). FM and FFM were calculated based on height-weight models derived from bioelectrical impedance studies. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Confounder-adjusted linear and logistic regressions were used to associate changes in anthropometric markers with changes in blood pressure, incident hypertension, and incident normalization of blood pressure. RESULTS: In a pooled dataset including all four studies, increments in body weight, WC, FM, and FFM were statistically significantly associated with incident hypertension and changes in systolic and diastolic blood pressure over time. Decreases in body weight, FM, and FFM were significantly associated with incident normalization of blood pressure. CONCLUSIONS: Our data suggests that the well-established association between obesity and blood pressure levels might be more related to body composition rather than to total body weight per se. Our findings indicate that gaining or losing FFM has substantial impact on the development or reversion of hypertension.

Longitudinal association of short-term, metronome-paced heart rate variability and echocardiographically assessed cardiac structure at a 4-year follow-up: results from the prospective, population-based CARLA cohort.

AIMS: To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters. METHODS AND RESULTS: Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure. CONCLUSION: In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations.

Prognostic relevance of the interaction between short-term, metronome-paced heart rate variability, and inflammation: results from the population-based CARLA cohort study.

AIMS: To determine the interaction between HRV and inflammation and their association with cardiovascular/all-cause mortality in the general population. METHODS AND RESULTS: Subjects of the CARLA study (n = 1671; 778 women, 893 men, 45-83 years of age) were observed for an average follow-up period of 8.8 years (226 deaths, 70 cardiovascular deaths). Heart rate variability parameters were calculated from 5-min segments of 20-min resting electrocardiograms. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and soluble tumour necrosis factor-alpha receptor type 1 (sTNF-R1) were measured as inflammation parameters. The HRV parameters determined included the standard deviation of normal-to-normal intervals (SDNN), the root-mean-square of successive normal-interval differences (RMSSD), the low- and high-frequency (HF) power, the ratio of both, and non-linear parameters [Poincaré plot (SD1, SD2, SD1/SD2), short-term detrended fluctuation analysis]. We estimated hazard ratios by using covariate-adjusted Cox regression for cardiovascular and all-cause mortality incorporating an interaction term of HRV/inflammation parameters. Relative excess risk due to interactions (RERIs) were computed. We found an interaction effect of sTNF-R1 with SDNN (RERI: 0.5; 99% confidence interval (CI): 0.1-1.0), and a weaker effect with RMSSD (RERI: 0.4; 99% CI: 0.0-0.9) and HF (RERI: 0.4; 99% CI: 0.0-0.9) with respect to cardiovascular mortality on an additive scale after covariate adjustment. Neither IL-6 nor hsCRP showed a significant interaction with the HRV parameters. CONCLUSION: A change in TNF-α levels or the autonomic nervous system influences the mortality risk through both entities simultaneously. Thus, TNF-α and HRV need to be considered when predicating mortality.

Association of Serum Thyrotropin with Anthropometric Markers of Obesity in the General Population.

BACKGROUND: Except from associations study with body weight, there are few longitudinal data regarding the association between thyroid function and anthropometric measurements such as waist circumference, waist-to-hip ratio, or waist-to height ratio. OBJECTIVE: This study aimed to investigate the association of thyrotropin (TSH) at baseline with changes in different anthropometric markers between baseline and follow-up in the general population. METHOD: Data were used from four population-based longitudinal cohort studies and one population-based cross-sectional study. A total of 16,902 (8204 males) subjects aged 20-95 years from the general population were studied. Body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Multivariable median regression models were calculated adjusting for the following covariates: age, sex, baseline value of the respective anthropometric marker, smoking status, follow-up-time period, and study site. RESULTS: In cross-sectional analyses, serum TSH within the reference range was positively associated with waist circumference (ß = 0.94 cm [confidence interval (CI) 0.56-1.32]) and waist-to-height-ratio (ß = 0.029 [CI 0.017-0.042]). These associations were also present for the full range of TSH. In the longitudinal analyses, serum TSH at baseline was inversely associated with a five-year change of all considered anthropometric measures within the prior defined study-specific reference range, as well as in the full range of serum TSH. CONCLUSION: High TSH serum levels were positively associated with current anthropometric markers, even in the study-specific reference ranges. In contrast, high TSH serum levels were associated with decreased anthropometric markers over a time span of approximately five years. Further research is needed to determine possible clinical implications as well as public health consequences of these findings.

Association of late-life changes in blood pressure and cognitive status.

BACKGROUND: Disagreement exists on the association between changes in blood pressure and cognitive impairment. We aimed to examine whether 4-year changes in systolic and diastolic blood pressure (SBP and DBP) are associated with cognitive status in a representative sample of older men and women. METHODS: Analysis of longitudinal data from 854 participants of a population-based German sample (aged 60-87 years) was performed with standard cognitive screening and blood pressure measurements. Effects of changes in SBP and DBP (10 mmHg and 5 mmHg respectively as unit of regression effect measure) on cognitive status were evaluated using non-parametric and linear regression modeling. RESULTS: No clear associations were seen between changes in SBP or in DBP and cognitive scores. Small effects were found after stratification for sex and hypertension awareness. Specifically, larger decreases in SBP were associated with higher cognitive scores in those men aware of their hypertension (10 mmHg decrease in SBP, ß = -0.26, 95% CI: -0.51 to -0.02) and men with controlled hypertension (10 mmHg decrease in SBP, ß = -0.44, 95% CI: -0.92 to -0.03). Additionally larger increases in DBP were associated with higher cognitive scores in men with controlled hypertension (5 mmHg increase in DBP, ß = 0.67, 95% CI: 0.19-1.15). For women aware of their hypertension, larger decreases in DBP were associated with higher cognitive scores (5 mmHg decrease in DBP, ß = -0.26; 95%CI: -0.51 to -0.01). CONCLUSIONS: Changes in blood pressure were only weakly associated with cognitive status. Specifically, decreases in SBP were associated with higher cognitive scores in men aware of their hypertension and especially those that were medically controlled.

Socioeconomic status and anthropometric changes-A meta-analytic approach from seven German cohorts.

OBJECTIVE: To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population. METHODS: Longitudinal data of 56,556 participants aged 18-83 years from seven population-based German cohort studies (CARLA, SHIP, KORA, DEGS, EPIC-Heidelberg, EPIC-Potsdam, PopGen) were analyzed by meta-analysis using a random-effects model. The indicators of SES were education and household income. RESULTS: On average, all participants gained weight and increased their waist circumference over the study's follow-up period. Men and women in the low education group had a 0.1 percentage points greater annual increase in weight (95% CI men: 0.06-0.20; and women: 0.06-0.12) and waist circumference (95% CI men: 0.01-0.45; and women: 0.05-0.22) than participants in the high education group. Women with low income had a 0.1 percentage points higher annual increase in weight (95% CI 0.00-0.15) and waist circumference (95% CI 0.00-0.14) than women with high income. No association was found for men between income and obesity markers. CONCLUSIONS: Participants with lower SES (education and for women also income) gained more weight and waist circumference than those with higher SES. These results underline the necessity to evaluate the risk of weight gain based on SES to develop more effective preventive measures.

QT interval, general mortality and the role of echocardiographic parameters of left ventricular hypertrophy: Results from the prospective, population-based CARLA study.

BACKGROUND: There is convincing evidence of an association between the QT interval on electrocardiograms and general mortality. However, results are inconclusive regarding the extent to which this association depends on ventricular mass and size. METHODS: Data were obtained from the prospective, population-based CARLA study, with a mean follow-up of 8.8 years, after exclusion of subjects with atrial fibrillation (919 men, 797 women aged 45-83 years remained eligible). Echocardiographic parameters were left ventricular mass index, left ventricular diastolic dimension index, diastolic interventricular septum thickness, diastolic left ventricular posterior wall and the relative left ventricular wall thickness. Heart rate-corrected QT interval (QTc) was measured with standard 12-lead electrocardiograms using the MEANS algorithm. The association between QTc and survival was modelled using Cox-regression models (crude- and covariate-adjusted). Values were standardized by dividing the QTc by the standard deviation. The association between QTc and survival was assessed in terms of tertiles of echocardiographic parameters. RESULTS: In covariate-adjusted models, QTc was associated with general mortality (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03, 1.38). Compared with higher tertiles, subjects in the lowest tertile of left ventricular mass index (HR=1.73, 95% CI: 1.26, 2.36) showed the strongest association with general mortality, which was also true for the lowest tertile of diastolic left ventricular posterior wall thickness (HR=1.49, 95% CI: 1.10, 2.02). CONCLUSION: In the general population, the association between QTc and general mortality is strongest in subjects with low left ventricular mass index and diastolic thickness of the left ventricular posterior wall, thus the prognostic value of QTc needs to be interpreted with regard to these echocardiographic parameters.

Performance of Sokolow-Lyon index in detection of echocardiographically diagnosed left ventricular hypertrophy in a normal Eastern German population - results of the CARLA study.

BACKGROUND: Arterial hypertension is a common disease with high prevalence in the general population. Left ventricular hypertrophy (LVH) is an independent risk factor in arterial hypertension. Electrocardiographic indices like the Sokolow-Lyon index (SLI) are recommended as diagnostic screening methods for LVH. We assessed the diagnostic performance of the SLI in a cohort of a large general population. METHODS: We used electrocardiographic and echocardiographic data from the prospective, population-based cohort study CARdio-vascular Disease, Living and Ageing in Halle (CARLA). Linear and logistic regression models were used to assess the association of SLI with LVH. To assess the impact of the body-mass-index (BMI), we performed interaction analyses. RESULTS: AUC of SLI to predict LVH was 55.3 %, sensitivity of the SLI was 5 %, specificity 97 %. We found a significant association of SLI after covariate-adjustment with echocardiographically detected LVH (increase of left-ventricular mass index, LVMI 7.0 g/m(2) per 1 mV increase of SLI, p < 0.0001). However, this association was mainly caused by an association of SLI with the left-ventricular internal diameter (LVIDd, increase of 0.06 cm/m(2) per 1 mV increase of SLI, p < 0.0001). In obese (BMI > 30 kg/m(2)) we found the strongest association with an increase of 9.2 g/m(2) per 1 mV. CONCLUSIONS: Although statistically significant, relations of SLI and echocardiographic parameters of LVH were weak and mainly driven by the increase in LVIDd, implicating a more eccentric type of LVH in the collective. The relations were strongest when obese subjects were taken into account. Our data do not favour the SLI as a diagnostic screening test to identify patients at risk for LVH, especially in non-obese subjects without eccentric LVH.

Prevalence and Incidence of Hypertension in the General Adult Population: Results of the CARLA-Cohort Study.

Hypertension is a leading cause of cardiovascular disease. There are very few studies dealing with the incidence of hypertension and changes in blood pressure (BP) over time. We aimed to evaluate the prevalence and incidence of hypertension within an adult population-based cohort.The sample included 967 men and 812 women aged 45 to 83 years at baseline, 1436 subjects completed follow-up1 after 4 years and 1079 completed follow-up2 after 9 years. BP was measured according to a standardized protocol with oscillometric devices and hypertension was defined as mean systolic BP (SBP) ≥140  mmHg and/or diastolic BP (DBP) ≥90  mmHg and/or use of antihypertensive medication if hypertension was known. We examined prevalence and incidence of hypertension, by age and sex.The age-standardized prevalence of hypertension at baseline was 74.3% for men and 70.2% for women. The age-standardized annual incidence rate of hypertension for men was 8.6 (95% confidence interval [95% CI] 4.3-12.9) for follow-up period1 and 5.4 (95% CI 2.8-10.6) for follow-up period2 and for women 8.2 (95% CI 3.6-12.8) for follow-up1 and 5.6 (95%CI 2.7-11.4) for follow-up2. A clear decrease in SBP and DBP between baseline and follow-up1 and follow-up2 was seen, accompanied by an increase in anti-hypertensive medication consumption and a higher awareness of the condition.Hypertension prevalence and incidence in the CARLA Study appear to be elevated compared with other studies. The decrease of BP over time seems to be caused by improved hypertension control due to interventional effects of our observational study and improved health care.

Evaluation of a questionnaire to assess selected infectious diseases and their risk factors : findings of a multicenter study.

BACKGROUND/OBJECTIVES: The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called "ID Screen") for feasibility and validity. METHODS: From August-November 2011, 435 participants between the ages of 20-69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents' registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure "immune status" and "susceptibility to infections", multivariate analysis was used. RESULTS: The overall practicability was good and most items were well understood, demonstrated by < 2/33 missing questions per questionnaire and only three variables: vaccination for influenza and pneumococci and infection with chickenpox had a frequency > 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach's α < 0.5). This is corroborated by the extraction of more than one factor with a Kaiser-Meyer-Olkin measure of 0.6 instead of a unidimensional latent construct for "immune status". CONCLUSION: All in all, the ID Screen is a good and reliable tool to measure infectious diseases as risk factors and outcome in general, but requires a better translation of infection specific terms into lay person terms. For the assessment of the overall immune status, the tool has strong limitations. Vaccinations status should also rather be assessed based on vaccination certificates than on participants' recall.

Inflammation and renal function after a four-year follow-up in subjects with unimpaired glomerular filtration rate: results from the observational, population-based CARLA cohort.

BACKGROUND: There is evidence that chronic inflammation is associated with the progression/development of chronic renal failure; however, relations in subjects with preserved renal function remain insufficiently understood. OBJECTIVE: To examine the association of inflammation with the development of renal failure in a cohort of the elderly general population. METHODS: After excluding subjects with reduced estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m2) and missing data, the cohort incorporated 785 men and 659 women (aged 45-83 years). Follow-up was performed four years after baseline. Covariate adjusted linear and logistic regression models were used to assess the association of plasma/serum concentrations of soluble tumour necrosis factor receptor 1 (sTNF-R1), C-reactive protein (CRP), and interleukin 6 (IL-6) with change in eGFR/creatinine. The areas under the curve (AUCs) from receiver operating characteristics (ROCs) were estimated. RESULTS: In adjusted models sTNF-R1 was distinctively associated with a decline in eGFR in men (0.6 mL/min/1.73 m2 per 100 pg/mL sTNF-R1; 95% CI: 0.4-0.8), but not in women. A similar association could not be found for CRP or IL-6. Estimates of sTNF-R1 in the cross-sectional analyses were similar between sexes, while CRP and IL-6 were not relevantly associated with eGFR/creatinine. CONCLUSION: In the elderly male general population with preserved renal function sTNF-R1 predicts the development of renal failure.

Inflammation and prolonged QT time: results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study.

BACKGROUND: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. OBJECTIVE: To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population. METHODS: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. RESULTS: After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. CONCLUSION: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

Sex-specific associations between thyrotropin and serum lipid profiles.

BACKGROUND: Population-based studies investigating the sex-specific association between thyrotropin (TSH) levels and serum lipid concentrations are scarce. We examined the association between TSH and total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in men and women from the general population. Furthermore, the association with TSH outside and within the reference range and lipid levels was studied. METHODS: Individual data of 13,571 men and women without lipid medication of four population-based studies conducted in Western European adults were pooled for cross-sectional analyses. The association between TSH levels and lipid concentrations were analyzed by calculating sex-specific multivariable median regression models. RESULTS: In the pooled population, serum TSH levels were significantly positively associated with triglyceride values in men and with total cholesterol, LDL cholesterol, and triglyceride values in women. In the pooled male population, low serum TSH levels (<3.0 mIU/L) were significantly associated with lower total cholesterol, while high serum TSH levels (≥ 3.0 mIU/L) were associated with higher triglyceride values. In the pooled female population, low serum TSH levels were significantly associated with lower total cholesterol, LDL cholesterol, and HDL cholesterol. High TSH levels were associated with higher total cholesterol and LDL cholesterol in the pooled female population. In both sexes, serum TSH levels within the reference range (0.3-3.0 mIU/L) were significantly positively associated with triglyceride concentrations. CONCLUSIONS: Increasing levels of TSH were associated with a less favorable lipid profile in both men and women from the general population. In both sexes, TSH levels within the reference range were significantly positively associated with triglyceride concentrations.