Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

Time trends in stroke incidence and in prevalence of risk factors in Southern Germany, 1989 to 2008/09

In prior studies, stroke incidence has mainly shown either declining time trends or stable rates in high-income countries. Changes could partially be linked to trends in classic cardiovascular disease (CVD) risk factors. In the present study, we analyzed the incidence of stroke in parallel with the prevalence of CVD risk factors over time in a German population. Data from three independent population-based MONICA/KORA Augsburg surveys conducted in 1989/90 (S2), 1994/95 (S3), and 1999/2001 (S4) were used to calculate age-standardized incidence rates (IR) of first-ever stroke over eight years from each baseline survey. Furthermore, the age-standardized prevalence rates of CVD risk factors were analyzed for these surveys. Changes in IR or prevalence were considered significantly different if their 95% confidence intervals (CI) did not overlap. The age-standardized IR of stroke showed no significant time trend (S2: IR = 203.4 per 100,000 person-years; CI 176.4-233.4, S3: IR = 225.6; 197.1-257.0, S4: IR = 209.9; CI 182.4-240.3). In agreement, the prevalence of the CVD risk factors was quite stable over time, showing divergent, but mostly non-significant changes. However, due to the aging Western societies and the longer survival time of stroke patients, the total number of stroke patients in the population will increase even with a stable IR

Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes

BACKGROUND: Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D) supplements, although the underlying mechanisms are not clear. OBJECTIVE: Thus, we analyzed the associations between Ca and vitamin D supplementation as well as serum concentrations of Ca and 25-hydroxyvitamin D (25(OH)D) and subclinical cardiovascular disease (CVD) phenotypes, namely intima-media thickness, ankle-brachial-index (ABI), intermittent claudication, and atrial fibrillation (AF). DESIGN: Data of 1601 participants aged 50-81 years of the population-based cross-sectional Cooperative Health Research in the Region of Augsburg (KORA) F4 study in Germany were analyzed. Logistic and linear regression models were used to estimate odds ratios (OR) (95% confidence intervals (CI)) and β-estimates (p-values), respectively. RESULTS: Regular Ca supplementation showed a significant positive association with the presence of AF after multivariable adjustment (OR = 3.89; 95% CI 1.28-11.81). Higher serum 25(OH)D concentrations were independently associated with a lower prevalence of asymptomatic peripheral arterial disease as assessed by ABI measurements (β = 0.007; p = 0.01). No other significant associations between supplementation or serum concentrations of Ca or vitamin D and CVD phenotypes were identified. CONCLUSIONS: Although based on few cases the finding of a significant higher prevalence of AF in Ca supplement users hints at one possible mechanism that may contribute to an increased risk of myocardial infarction and stroke. The observed association between serum 25(OH)D and ABI supports results from other studies

Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA‐ADHF‐DZHK10 trial

Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right‐sided haemodynamic congestion. The CAVA‐ADHF‐DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA‐ADHF‐DZHK10 is a randomized, controlled, patient‐blinded, multicentre, parallel‐group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion‐related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N‐terminal pro‐brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA‐ADHF‐DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF

Preformed donor-specific HLA antibodies in living and deceased donor transplantation: a multicenter study

Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P= 3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA = 3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA >= 3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation

[Nighttime transportation noise annoyance in Germany: personal and regional differences in the German National Cohort Study].

BACKGROUND: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors. OBJECTIVE: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance? MATERIALS AND METHODS: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model. RESULTS: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group. CONCLUSION: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors

[Blood pressure measurement in the NAKO German National Cohort (GNC) - differences in methods, distribution of blood pressure values, and awareness of hypertension compared to other population-based studies in Germany].

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Blutdruckmessung in der NAKO: methodische Unterschiede, Blutdruckverteilung und Bekanntheit der Hypertonie im Vergleich zu anderen bevölkerungsbezogenen Studien in Deutschland

HINTERGRUND: Arterielle Hypertonie ist einwichtiger Risikofaktor für Herz-Kreislauf-Er-krankungen. Epidemiologische Studien führen meist drei konsekutive Blutdruckmessungen durch. Der 1. Messwert wird für Auswertungen verworfen, da dieser am stärksten durch vorhergehende Aktivitäten beeinflusst sein kann. Aus zeitlichen Gründen wurden in der NAKO Gesundheitsstudie nur zwei Messungen durchgeführt. FRAGESTELLUNG: Die vorliegende Analyse untersucht Auswirkungen methodischer Unterschiede bei der Blutdruckmessungauf die Hypertoniehäufigkeit und mittlere Blutdruckwerte anhand eines Vergleichsder ersten Hälfte der NAKO-Teilnehmenden(nur 2 Messungen) mit 5 deutschen populationsbasierten Studien (3 Messungen). MATERIAL UND METHODEN: Es wurden Daten der Teilnehmenden aus der NAKO (erste 101.816 Personen), der bundesweiten Studie zur Gesundheit Erwachsener des Robert Koch-Instituts (DEGS1) und aus 4 regionalen populationsbasierten Kohortenstudien (CARLA, HNR, KORA, SHIP) analysiert. Alters- und geschlechtsspezifische mittlere Blutdruckwerte und Hypertoniehäufigkeiten wurden auf Basis des 2. Messwertes, des Mittelwerts aus 1. und 2. sowie aus 2. und 3. Messung berechnet. ERGEBNISSE: Die mittleren Blutdruckwerte der beiden aktuellsten Studien (NAKO und DEGS1) sind sehr ähnlich und niedriger als in den anderen Studien. Die Differenz zwischen dem 2. Messwert und dem Mittelwert aus 2. und 3. Messung ist gering (maximale mittlere Abweichung: 1,5mmHg systolisch), jedoch ist die mittels des 2. Messwertes berechnete Hypertoniehäufigkeit der Bevölkerung höher als bei Verwendung des Mittelwertsaus 2. und 3. Messung. DISKUSSION: Die Ergebnisse der vorliegenden Analyse zeigen, dass für die wissenschaftliche Auswertung der NAKO-Daten die Verwendung des 2. Blutdruckmesswerts zu empfehlen ist.BACKGROUND: Arterial hypertension is an important risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. OBJECTIVES. The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). MATERIALS AND METHODS: Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate age-and sex-specific mean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). RESULTS: The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mmHg systolic blood pressure), but leads to higher estimated hypertension frequencies. CONCLUSIONS: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data