Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO).

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Projected health and economic impacts of sugar-sweetened beverage taxation in Germany: A cross-validation modelling study.

BACKGROUND: Taxes on sugar-sweetened beverages (SSBs) have been implemented globally to reduce the burden of cardiometabolic diseases by disincentivizing consumption through increased prices (e.g., 1 peso/litre tax in Mexico) or incentivizing industry reformulation to reduce SSB sugar content (e.g., tiered structure of the United Kingdom [UK] Soft Drinks Industry Levy [SDIL]). In Germany, where no tax on SSBs is enacted, the health and economic impact of SSB taxation using the experience from internationally implemented tax designs has not been evaluated. The objective of this study was to estimate the health and economic impact of national SSBs taxation scenarios in Germany. METHODS AND FINDINGS: In this modelling study, we evaluated a 20% ad valorem SSB tax with/without taxation of fruit juice (based on implemented SSB taxes and recommendations) and a tiered tax (based on the UK SDIL) in the German adult population aged 30 to 90 years from 2023 to 2043. We developed a microsimulation model (IMPACTNCD Germany) that captures the demographics, risk factor profile and epidemiology of type 2 diabetes, coronary heart disease (CHD) and stroke in the German population using the best available evidence and national data. For each scenario, we estimated changes in sugar consumption and associated weight change. Resulting cases of cardiometabolic disease prevented/postponed and related quality-adjusted life years (QALYs) and economic impacts from healthcare (medical costs) and societal (medical, patient time, and productivity costs) perspectives were estimated using national cost and health utility data. Additionally, we assessed structural uncertainty regarding direct, body mass index (BMI)-independent cardiometabolic effects of SSBs and cross-validated results with an independently developed cohort model (PRIMEtime). We found that SSB taxation could reduce sugar intake in the German adult population by 1 g/day (95%-uncertainty interval [0.05, 1.65]) for a 20% ad valorem tax on SSBs leading to reduced consumption through increased prices (pass-through of 82%) and 2.34 g/day (95%-UI [2.32, 2.36]) for a tiered tax on SSBs leading to 30% reduction in SSB sugar content via reformulation. Through reductions in obesity, type 2 diabetes, and cardiovascular disease (CVD), 106,000 (95%-UI [57,200, 153,200]) QALYs could be gained with a 20% ad valorem tax and 192,300 (95%-UI [130,100, 254,200]) QALYs with a tiered tax. Respectively, €9.6 billion (95%-UI [4.7, 15.3]) and €16.0 billion (95%-UI [8.1, 25.5]) costs could be saved from a societal perspective over 20 years. Impacts of the 20% ad valorem tax were larger when additionally taxing fruit juice (252,400 QALYs gained, 95%-UI [176,700, 325,800]; €11.8 billion costs saved, 95%-UI [€6.7, €17.9]), but impacts of all scenarios were reduced when excluding direct health effects of SSBs. Cross-validation with PRIMEtime showed similar results. Limitations include remaining uncertainties in the economic and epidemiological evidence and a lack of product-level data. CONCLUSIONS: In this study, we found that SSB taxation in Germany could help to reduce the national burden of noncommunicable diseases and save a substantial amount of societal costs. A tiered tax designed to incentivize reformulation of SSBs towards less sugar might have a larger population-level health and economic impact than an ad valorem tax that incentivizes consumer behaviour change only through increased prices.

Assessment of short-term heat effects on cardiovascular mortality and vulnerability factors using small area data in Europe.

BACKGROUND: Short-term associations between heat and cardiovascular disease (CVD) mortality have been examined mostly in large cities. However, different vulnerability and exposure levels may contribute to spatial heterogeneity. This study assessed heat effects on CVD mortality and potential vulnerability factors using data from three European countries, including urban and rural settings. METHODS: We collected daily counts of CVD deaths aggregated at the small-area level in Norway (small-area level: municipality), England and Wales (lower super output areas), and Germany (district) during the warm season (May-September) from 1996 to 2018. Daily mean air temperatures estimated by spatial-temporal models were assigned to each small area. Within each country, we applied area-specific Quasi-Poisson regression using distributed lag nonlinear models to examine the heat effects at lag 0-1 days. The area-specific estimates were pooled by random-effects meta-analysis to derive country-specific and overall heat effects. We examined individual- and area-level heat vulnerability factors by subgroup analyses and meta-regression, respectively. RESULTS: We included 2.84 million CVD deaths in analyses. For an increase in temperature from the 75th to the 99th percentile, the pooled relative risk (RR) for CVD mortality was 1.14 (95% CI: 1.03, 1.26), with the country-specific RRs ranging from 1.04 (1.00, 1.09) in Norway to 1.24 (1.23, 1.26) in Germany. Heat effects were stronger among women [RRs (95% CIs) for women and men: 1.18 (1.08, 1.28) vs. 1.12 (1.00, 1.24)]. Greater heat vulnerability was observed in areas with high population density, high degree of urbanization, low green coverage, and high levels of fine particulate matter. CONCLUSION: This study provides evidence for the heat effects on CVD mortality in European countries using high-resolution data from both urban and rural areas. Besides, we identified individual- and area-level heat vulnerability factors. Our findings may facilitate the development of heat-health action plans to increase resilience to climate change.

Associations of Migration, Socioeconomic Position and Social Relations With Depressive Symptoms - Analyses of the German National Cohort Baseline Data.

Objectives: We analyze whether the prevalence of depressive symptoms differs among various migrant and non-migrant populations in Germany and to what extent these differences can be attributed to socioeconomic position (SEP) and social relations. Methods: The German National Cohort health study (NAKO) is a prospective multicenter cohort study (N = 204,878). Migration background (assessed based on citizenship and country of birth of both participant and parents) was used as independent variable, age, sex, Social Network Index, the availability of emotional support, SEP (relative income position and educational status) and employment status were introduced as covariates and depressive symptoms (PHQ-9) as dependent variable in logistic regression models. Results: Increased odds ratios of depressive symptoms were found in all migrant subgroups compared to non-migrants and varied regarding regions of origins. Elevated odds ratios decreased when SEP and social relations were included. Attenuations varied across migrant subgroups. Conclusion: The gap in depressive symptoms can partly be attributed to SEP and social relations, with variations between migrant subgroups. The integration paradox is likely to contribute to the explanation of the results. Future studies need to consider heterogeneity among migrant subgroups whenever possible.

Health and economic impact of improved glucose, blood pressure and lipid control among German adults with type 2 diabetes: a modelling study.

AIMS/HYPOTHESIS: The aim of this study was to estimate the long-term health and economic consequences of improved risk factor control in German adults with type 2 diabetes. METHODS: We used the UK Prospective Diabetes Study Outcomes Model 2 to project the patient-level health outcomes and healthcare costs of people with type 2 diabetes in Germany over 5, 10 and 30 years. We parameterised the model using the best available data on population characteristics, healthcare costs and health-related quality of life from German studies. The modelled scenarios were: (1) a permanent reduction of HbA1c by 5.5 mmol/mol (0.5%), of systolic BP (SBP) by 10 mmHg, or of LDL-cholesterol by 0.26 mmol/l in all patients, and (2) achievement of guideline care recommendations for HbA1c (≤53 mmol/mol [7%]), SBP (≤140 mmHg) or LDL-cholesterol (≤2.6 mmol/l) in patients who do not meet the recommendations. We calculated nationwide estimates using age- and sex-specific quality-adjusted life year (QALY) and cost estimates, type 2 diabetes prevalence and population size. RESULTS: Over 10 years, a permanent reduction of HbA1c by 5.5 mmol/mol (0.5%), SBP by 10 mmHg or LDL-cholesterol by 0.26 mmol/l led to per-person savings in healthcare expenditures of €121, €238 and €34, and 0.01, 0.02 and 0.015 QALYs gained, respectively. Achieving guideline care recommendations for HbA1c, SBP or LDL-cholesterol could reduce healthcare expenditure by €451, €507 and €327 and gained 0.03, 0.05 and 0.06 additional QALYs in individuals who did not meet the recommendations. Nationally, achieving guideline care recommendations for HbA1c, SBP and LDL-cholesterol could reduce healthcare costs by over €1.9 billion. CONCLUSIONS/INTERPRETATION: Sustained improvements in HbA1c, SBP and LDL-cholesterol control among diabetes patients in Germany can lead to substantial health benefits and reduce healthcare expenditures.

Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to acute and chronic health effects through the suggested pathways of oxidative stress and inflammation. However, evidence is still limited. We aimed to investigate jointly the relationship of PAHs, oxidative stress, and inflammation. METHODS: We measured 13 biomarkers of PAH exposure (n = 6: hydroxylated polycyclic aromatic hydrocarbons, [OH-PAHs]), oxidative stress (n = 6: malondialdehyde (MDA); 8-hydroxy-2'-deoxyguanosine (8-OHdG); and 4 representatives of the compound class of F2α-isoprostanes) in urine, and inflammation (n = 1: high-sensitivity C-reactive protein, [hs-CRP]) in serum from 400 participants at the second follow-up (2013/2014) of the German KORA survey S4. Multiple linear regression models were applied to investigate the interplay between biomarkers. RESULTS: Concentrations of biomarkers varied according to sex, age, smoking status, season, and a history of obesity, diabetes, or chronic kidney disease. All OH-PAHs were significantly and positively associated with oxidative stress biomarkers. An interquartile range (IQR) increase in sum OH-PAHs was associated with a 13.3% (95% CI: 9.9%, 16.9%) increase in MDA, a 6.5% (95% CI: 3.5%, 9.6%) increase in 8-OHdG, and an 8.4% (95% CI: 6.6%, 11.3%) increase in sum F2α-isoprostanes. Associations were more pronounced between OH-PAHs and F2α-isoprostanes but also between OH-PAHs and 8-OHdG for participants with potential underlying systemic inflammation (hs-CRP ≥ 3 mg/L). We observed no association between OH-PAHs and hs-CRP levels. While 8-OHdG was significantly positively associated with hs-CRP (13.7% [95% CI: 2.2%, 26.5%] per IQR increase in 8-OHdG), F2α-isoprostanes and MDA indicated only a positive or null association, respectively. CONCLUSION: The results of this cross-sectional study suggest, at a population level, that exposure to PAHs is associated with oxidative stress even in a low exposure setting. Oxidative stress markers, but not PAHs, were associated with inflammation. Individual risk factors were important contributors to these processes and should be considered in future studies. Further longitudinal studies are necessary to investigate the causal chain of the associations.

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.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Whole-Body Magnetic Resonance Imaging in the Large Population-Based German National Cohort Study: Predictive Capability of Automated Image Quality Assessment for Protocol Repetitions.

BACKGROUND: Reproducible image quality is of high relevance for large cohort studies and can be challenging for magnetic resonance imaging (MRI). Automated image quality assessment may contribute to conducting radiologic studies effectively. PURPOSE: The aims of this study were to assess protocol repetition frequency in population-based whole-body MRI along with its effect on examination time and to examine the applicability of automated image quality assessment for predicting decision-making regarding repeated acquisitions. MATERIALS AND METHODS: All participants enrolled in the prospective, multicenter German National Cohort (NAKO) study who underwent whole-body MRI at 1 of 5 sites from 2014 to 2016 were included in this analysis (n = 11,347). A standardized examination program of 12 protocols was used. Acquisitions were carried out by certified radiologic technologists, who were authorized to repeat protocols based on their visual perception of image quality. Eleven image quality parameters were derived fully automatically from the acquired images, and their discrimination ability regarding baseline acquisitions and repetitions was tested. RESULTS: At least 1 protocol was repeated in 12% (n = 1359) of participants, and more than 1 protocol in 1.6% (n = 181). The repetition frequency differed across protocols (P < 0.001), imaging sites (P < 0.001), and over the study period (P < 0.001). The mean total scan time was 62.6 minutes in participants without and 67.4 minutes in participants with protocol repetitions (mean difference, 4.8 minutes; 95% confidence interval, 4.5-5.2 minutes). Ten of the automatically derived image quality parameters were individually retrospectively predictive for the repetition of particular protocols; for instance, "signal-to-noise ratio" alone provided an area under the curve of 0.65 (P < 0.001) for repetition of the Cardio Cine SSFP SAX protocol. Combinations generally improved prediction ability, as exemplified by "image sharpness" plus "foreground ratio" yielding an area under the curve of 0.89 (P < 0.001) for repetition of the Neuro T1w 3D MPRAGE protocol, versus 0.85 (P < 0.001) and 0.68 (P < 0.001) as individual parameters. CONCLUSIONS: Magnetic resonance imaging protocol repetitions were necessary in approximately 12% of scans even in the highly standardized setting of a large cohort study. Automated image quality assessment shows predictive value for the technologists' decision to perform protocol repetitions and has the potential to improve imaging efficiency.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

BACKGROUND: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS: Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

Natriuretic Peptides and Risk of Type 2 Diabetes: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

OBJECTIVE: Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD. RESEARCH DESIGN AND METHODS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models. RESULTS: Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19]; P multiplicative interaction = 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs. 0.81 [0.66; 0.99]; P multiplicative interaction = 0.236). CONCLUSIONS: NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.

Association of sex-specific differences in lipoprotein(a) concentrations with cardiovascular mortality in individuals with type 2 diabetes mellitus.

BACKGROUND: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. METHODS: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. RESULTS: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). CONCLUSIONS: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.

Utility Decrements Associated With Diabetes and Related Complications: Estimates From a Population-Based Study in Germany.

OBJECTIVES: Health utility decrement estimates for diabetes and complications are needed for parametrization of simulation models that aim to assess the cost-utility of diabetes prevention and care strategies. This study estimates health utility decrements associated with diabetes and cardiovascular and microvascular complications from a population-based German study. METHODS: Data were obtained from the population based cross-sectional KORA (Cooperative Health Research in the Augsburg Region) health questionnaire 2016 and comprised n = 1072 individuals with type 2 diabetes and n = 7879 individuals without diabetes. Health utility was assessed through the EQ-5D-5L. We used linear regression models with interaction terms between type 2 diabetes and different cardiovascular and microvascular complications while adjusting for demographic and socio-economic factors and other comorbidities. RESULTS: Type 2 diabetes (ß = -0.028, standard error [SE] = 0.014), stroke (ß = -0.070, SE = 0.010), cardiac arrhythmia (ß = -0.031, SE = 0.006), heart failure (ß = -0.073, SE = 0.009), coronary heart disease (ß = -0.028, SE = 0.010), myocardial infarction (ß = -0.020, SE = 0.011, estimates of main effect), and neuropathy (ß = -0.067, SE = 0.020), diabetic foot (ß = -0.042, SE = 0.030), nephropathy (ß = -0.032, SE = 0.025), and blindness (ß = -0.094, SE = 0.056, estimates of interaction terms) were negatively associated with health utility. The interaction term for diabetes x stroke (ß = -0.052, SE = 0.021) showed that the utility decrement for stroke is significantly larger in people with type 2 diabetes than in people without diabetes. CONCLUSIONS: Diabetes, cardiovascular, and microvascular conditions are associated with significant health utility decrements. Utility decrements for some conditions differ between people with and without type 2 diabetes. These results are of high relevance for the parametrization of decision analytic simulation models and applied health economic evaluations in the field of prevention and management of type 2 diabetes in Germany.

Living longer but less healthy: The female disadvantage in health expectancy. Results from the KORA-Age study.

OBJECTIVES: We explored the male-female health-survival paradox in the context of health expectancy (HE) at age 65 and thereafter, using three different morbidity measures and different severity cut-offs with and without adjustments for the share of nursing home residents. METHODS: HE at ages 65, 70, 75, 80, and 85 was estimated with the Sullivan method, linking morbidity prevalence from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study to 2016 Bavarian mortality data. Morbidity measures comprised deficit accumulation (Frailty Index, FI, cut-offs 0.08 and 0.25), disability (Health Assessment Questionnaire-Disability Index, HAQ-DI, cut-off >0) and participation (Global Activity Limitation Indicator, GALI, "limited" vs "not limited"). RESULTS: Morbidity data were available for 4083 participants (52.7% female). HE was lower in women than in men at all ages. Differences in morbidity prevalence, absolute HE, and health proportions of life expectancy (relative HE) increased with age for FI ≥ 0.25 and GALI, but not for HAQ-DI > 0 and FI > 0.08. Accounting for the share of nursing home residents resulted in a slight reduction of HE estimates but had no impact on estimated sex differences. CONCLUSIONS: In HE at age 65 and thereafter, women's health disadvantage was larger than their life expectancy advantage over men.

Toward targeted prevention: risk factors for prediabetes defined by impaired fasting glucose, impaired glucose tolerance and increased HbA1c in the population-based KORA study from Germany.

AIMS: To identify socioeconomic, behavioral and clinical factors that are associated with prediabetes according to different prediabetes definition criteria. METHODS: Analyses use pooled data of the population-based Cooperative Health Research in the Region of Augsburg (KORA) studies (n = 5312 observations aged ≥ 38 years without diabetes). Prediabetes was defined through either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or elevated HbA1c according to thresholds of the American Diabetes Association. Explanatory variables were regressed on prediabetes using generalized estimating equations. RESULTS: Mean age was 58.4 years; 50% had prediabetes (33% had IFG, 16% IGT, and 26% elevated HbA1c, 10% fulfilled all three criteria). Age, obesity, hypertension, low education, unemployment, statutory health insurance, urban residence and physical inactivity were associated with prediabetes. Male sex was a stronger risk factor for IFG (OR = 2.5; 95%-CI: 2.2-2.9) than for IGT or elevated HbA1c, and being unemployed was a stronger risk factor for IGT (OR = 3.2 95%-CI: 2.6-4.0) than for IFG or elevated HbA1c. CONCLUSIONS: The overlap of people with IFG, IGT and elevated HbA1c is small, and some factors are associated with only one criterion. Knowledge on sociodemographic and socioeconomic risk factors can be used to effectively target interventions to people at high risk for type 2 diabetes.

Diverging Trends in Age at First Myocardial Infarction: Evidence from Two German Population-Based Studies.

Little is known about trends in the age of onset of first myocardial infarction. Thus, we examined trends in the age of onset distribution of first myocardial infarction using two population-based datasets from Germany. First, we used German claims data based on an annual case number of approximately 2 million women and men covering the period from 2006 to 2016. Second, we used data from the KORA (Cooperative Health Research in the Region of Augsburg) Myocardial Infarction Registry covering the period from 2000-2016. Analyses were performed by means of quantile regression to estimate trends across the whole distribution of age of onset. Overall, NSample 1 = 69627 and NSample 2 = 9954 first myocardial infarctions were observed. In both samples, we found highly heterogeneous trends in age of onset. In men, we consistently found that age of onset increased before 50 and after 70 but decreased within this age bracket. For women, on the other hand, we consistently found that age of onset decreased for first myocardial infarctions before 70 but increased slightly or remained relatively stable thereafter. Therefore, late myocardial infarctions tended to occur later in life, while regular myocardial infarctions tended to occur earlier. These results suggest that in myocardial infarction, both morbidity compression and morbidity expansion might have occurred at the same time but for different parts of the age at onset distribution.

[Assessment of self-reported cardiovascular and metabolic diseases in the German National Cohort (GNC, NAKO Gesundheitsstudie): methods and initial results]. / Erfassung selbst berichteter kardiovaskulärer und metabolischer Erkrankungen in der NAKO Gesundheitsstudie: Methoden und erste Ergebnisse.

BACKGROUND: Data on self-reported cardiovascular and metabolic diseases are available for the first 100,000 participants of the population-based German National Cohort (GNC, NAKO Gesundheitsstudie). OBJECTIVES: To describe assessment methods and the frequency of self-reported cardiovascular and metabolic diseases in the German National Cohort. MATERIALS AND METHODS: Using a computer-based, standardized personal interview, 101,806 participants (20-75 years, 46% men) from 18 nationwide study centres were asked to use a predefined list to report medical conditions ever diagnosed by a physician, including cardiovascular or metabolic diseases. For the latter, we calculated sex-stratified relative frequencies and compared these with reference data. RESULTS: With regard to cardiovascular diseases, 3.5% of men and 0.8% of women reported to have ever been diagnosed with a myocardial infarction, 4.8% and 1.5% with angina pectoris, 3.5% and 2.5% with heart failure, 10.1% and 10.4% with cardiac arrhythmia, 2.7% and 1.8% with claudicatio intermittens, and 34.6% and 27.0% with arterial hypertension. The frequencies of self-reported diagnosed metabolic diseases were 8.1% and 5.8% for diabetes mellitus, 28.6% and 24.5% for hyperlipidaemia, 7.9% and 2.4% for gout, and 10.1% and 34.3% for thyroid diseases. Observed disease frequencies were lower than reference data for Germany. CONCLUSIONS: In the German National Cohort, self-reported cardiovascular and metabolic diseases diagnosed by a physician are assessed from all participants, therefore representing a data source for future cardio-metabolic research in this cohort.

[Physical activity in the German National Cohort (NAKO): use of multiple assessment tools and initial results]. / Körperliche Aktivität in der NAKO Gesundheitsstudie: erste Ergebnisse des multimodalen Erhebungskonzepts.

BACKGROUND: Physical activity is a complex behavior that is difficult to measure validly and reliably in large, population-based studies. Data on physical activity are available for the initial 100,000 participants of the German National Cohort. OBJECTIVES: To describe the baseline physical activity assessment in the cohort and to present initial descriptive results. MATERIAL AND METHODS: Physical activity was assessed using a combination of tools, including two self-administered questionnaires, the Questionnaire on Annual Physical Activity Pattern (QUAP) and the Global Physical Activity Questionnaire (GPAQ); a computer-based 24­h physical activity recall (cpar24); and 7­day accelerometry (Actigraph GT3X/+; ActiGraph, Pensacola, FL, USA). RESULTS: The availability of data varied between assessment instruments (QUAP: n = 16,372; GPAQ: n = 90,900; cpar24: n = 23,989; accelerometry: n = 35,218). Analyses across measurement tools showed that on average, women spent 75 to 216 min/d, and men spent 73 to 224 min/d in moderate or higher intensity total physical activity. Persons aged 20-39 years spent 66 to 200 min/d, and persons aged 40-69 years spent 78 to 244 min/d in moderate or higher intensity total physical activity. CONCLUSIONS: Initial baseline analyses of physical activity in this cohort show the value of using a combination of questionnaires, 24­h recalls, and a movement sensor. The comprehensive data collection represents a valuable resource for future analyses and will improve our understanding of the association between physical activity and disease prevention.

Bone marrow fat fraction assessment in regard to physical activity: KORA FF4-3-T MR imaging in a population-based cohort.

OBJECTIVES: To establish the effect of different degrees and kinds of physical activity on bone marrow fat (BMAT) content at different anatomical locations in a population-based cohort study undergoing whole-body MR imaging. METHODS: Subjects of the KORA FF4 study without known cardiovascular disease underwent BMAT fat fraction (FF) quantification in L1 and L2 vertebrae and femoral heads/necks (hip) via a 2-point T1-weighted VIBE Dixon sequence. BMAT-FF was calculated as mean value (fat image) divided by mean value (fat + water image). Physical activity was determined by self-assessment questionnaire regarding time spent exercising, non-exercise walking, non-exercise cycling, and job-related physical activity. RESULTS: A total of 385 subjects (96% of 400 available; 56 ± 9.1 years; 58% male) were included in the analysis. Exercise was distributed quite evenly (29% > 2 h/week; 31% ~ 1 h/week (regularly); 15% ~ 1 h/week (irregularly); 26% no physical activity). BMAT-FF was 52.6 ± 10.2% in L1, 56.2 ± 10.3% in L2, 87.4 ± 5.9% in the right hip, and 87.2 ± 5.9% in the left hip (all p < 0.001). Correlation of BMAT-FF between spine and hip was only moderate (r 0.42 to 0.46). Spinal BMAT-FF, but not hip BMAT-FF, was inversely associated with exercise > 2 h/week (p ≤ 0.02 vs. p ≥ 0.35, respectively). These associations remained significant after adjusting for age, gender, waist circumference, and glucose tolerance. No coherent association was found between BMAT-FF and physical activity in the less active groups. CONCLUSIONS: In our study, exercise was inversely correlated with vertebral BMAT-FF, but not hip BMAT-FF, when exercising for more than 2 h per week. Physical activity seems to affect the spine at least preferentially compared to the hip. KEY POINTS: • In our population-based cohort, at least 2 h of physical activity per week were required to show lower levels of bone marrow adipose tissue fat fraction in MRI. • Physical activity seems to affect bone marrow adipose tissue at least preferentially at the spine in contrast to the proximal femur.