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.

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project.

BACKGROUND: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. METHODS: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. RESULTS: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. CONCLUSION: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

Decomposing the educational gradient in allostatic load across European populations. What matters the most: differentials in exposure or in susceptibility?

BACKGROUND: We investigate whether socially disadvantaged individuals are more susceptible to the detrimental effects of smoking and alcohol intake on allostatic load (AL), a marker of physiological 'wear and tear', resulting from adaptation to chronic stress. METHODS: In a cross-sectional analysis, 27 019 men and 26 738 women aged 35-74 years were identified from 21 European cohorts in the BiomarCaRE consortium. We defined three educational classes (EDs) according to years of schooling and an AL score as the sum of z-scores of eight selected biomarkers from the cardiovascular, metabolic and inflammatory systems. We used the Oaxaca-Blinder decomposition to disentangle the ED gradient in AL score into the differential exposure (DE, attributable to different distribution of smoking and alcohol intake across EDs) and the differential susceptibility (DS, attributable to a different effect of risk factors on AL across EDs) components. RESULTS: Less-educated men (mean AL difference: 0.68, 95% CI 0.57 to 0.79) and women (1.52, 95% CI 1.40 to 1.64) had higher AL scores. DE accounted for 7% and 6% of the gradient in men and women, respectively. In men, combining smoking and alcohol intake, DS accounted for 42% of the gradient (smoking DS coefficient=0.177, 26% of the gradient; alcohol DS coefficient=0.109; 16%, not statistically significant). DS contribution increased to 69% in metabolic markers. DS estimates were consistent across age groups, irrespective of comorbidities and robust to unmeasured confounding. No DS was observed in women. CONCLUSIONS: In men, a DS mechanism substantially contributes to the educational class gradient in allostatic load.

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.

Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

Being born in the aftermath of World War II increases the risk for health deficit accumulation in older age: results from the KORA-Age study.

Morbidity trends may result from cohort experiences in critical developmental age. Our objective was to compare the health status of 65-71 year-olds who were in critical developmental age before (1937-June 1945), during (June 1945-June 1948) and after (June 1948-1950) the early reconstruction and food crisis (ERFC) period in Germany following World War II. Data originate from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study in Southern Germany. We used the 2008 baseline sample born 1937-1943 and the 2015 enrichment sample born 1944-1950. Health status was assessed as the number of accumulated health deficits using a Frailty Index (FI). Cohorts were defined based on co-occurrence of critical developmental age (gestation and the first 2 years of life) and the ERFC period. Cohort, age and sex effects on older-age health status were analyzed using generalized linear models. We included 590 (53% male) pre-war and war (PWW), 475 (51% male) ERFC and 171 post-currency reform (PCR) cohort participants (46% male). Adjusted for covariates, FI levels were significantly higher for the ERFC (Ratio 1.14, CL [1.06, 1.23]) but not for the PCR (Ratio 1.06, CL [0.94, 1.20]) as compared to the PWW cohort. Being in critical developmental age during the ERFC period increased FI levels in adults aged 65-71 years. Covariates did not explain these effects, suggesting a direct detrimental effect from being in critical developmental age during the ERFC period on older-age health. This expansion of morbidity in Germany was not detected in the PCR cohort.

Male sex and poverty predict abrupt health decline: Deficit accumulation patterns and trajectories in the KORA-Age cohort study.

Ageing individuals differ both in their deficit accumulation (DA) trajectories and resulting DA patterns (improvement, stability, gradual or abrupt decline). This heterogeneity is still incompletely understood. The objectives of this study were thus to identify determinants of DA trajectories and DA patterns in people aged 65 and older. Data originates from the 2009 baseline assessment and 2012 follow-up of the KORA (Cooperative Health Research in the Region of Augsburg)-Age study from Southern Germany. DA was measured with a Frailty Index (FI). The effects of socio-demographic, socio-economic and lifestyle factors were analyzed using generalized linear mixed models and multinomial regressions. FI scores were available for 1076 participants at baseline (mean age 76years, 50% female) and 808 participants at follow-up. Higher baseline FI levels were significantly associated with higher age, female sex, lower physical activity, moderate alcohol consumption and obesity. Longitudinal increase in FI levels over 3years was 31% (CL: [-3%; 77%]) independent of all examined predictors. The most frequent DA patterns were stability (59%) and gradual decline (30%). Compared to stability, higher age, male sex and low income predicted (mostly fatal) abrupt decline. In conclusion, several factors are associated with FI levels at baseline whereas the change in FI levels over time seems hardly modifiable. Thus, future research should investigate if the same factors predicting older-age FI levels constitute predictors of DA onset earlier in life. Towards the end of life, being male with low income may increase the risk for abrupt decline, indicating need for early detection.

Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies.

OBJECTIVE: To examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control on direct costs. DESIGN: Bottom-up excess cost analysis from a societal perspective based on population-based survey data. PARTICIPANTS: 9160 observations from 6803 individuals aged 31-96 years (9.6% with type 2 diabetes) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) studies in Southern Germany. OUTCOME MEASURES: Healthcare usage, productivity losses, and resulting direct and indirect costs. METHODS: Information on diabetes status, biomedical/sociodemographic variables, medical history and on healthcare usage and productivity losses was assessed in standardised interviews and examinations. Healthcare usage and productivity losses were costed with reference to unit prices and excess costs of type 2 diabetes were calculated using generalised linear models. RESULTS: Individuals with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (€3352 vs €1849) and 2.07 (1.51 to 2.84) times higher indirect (€4103 vs €1981) annual costs than those without diabetes. Cardiovascular complications, a long diabetes duration and treatment with insulin were significantly associated with increased direct costs; however, glycaemic control was only weakly insignificantly associated with costs. CONCLUSIONS: This study illustrates the substantial direct and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is needed to optimise care to avoid progression of the disease and costly complications.

Assessment of predictive performance in incomplete data by combining internal validation and multiple imputation.

BACKGROUND: Missing values are a frequent issue in human studies. In many situations, multiple imputation (MI) is an appropriate missing data handling strategy, whereby missing values are imputed multiple times, the analysis is performed in every imputed data set, and the obtained estimates are pooled. If the aim is to estimate (added) predictive performance measures, such as (change in) the area under the receiver-operating characteristic curve (AUC), internal validation strategies become desirable in order to correct for optimism. It is not fully understood how internal validation should be combined with multiple imputation. METHODS: In a comprehensive simulation study and in a real data set based on blood markers as predictors for mortality, we compare three combination strategies: Val-MI, internal validation followed by MI on the training and test parts separately, MI-Val, MI on the full data set followed by internal validation, and MI(-y)-Val, MI on the full data set omitting the outcome followed by internal validation. Different validation strategies, including bootstrap und cross-validation, different (added) performance measures, and various data characteristics are considered, and the strategies are evaluated with regard to bias and mean squared error of the obtained performance estimates. In addition, we elaborate on the number of resamples and imputations to be used, and adopt a strategy for confidence interval construction to incomplete data. RESULTS: Internal validation is essential in order to avoid optimism, with the bootstrap 0.632+ estimate representing a reliable method to correct for optimism. While estimates obtained by MI-Val are optimistically biased, those obtained by MI(-y)-Val tend to be pessimistic in the presence of a true underlying effect. Val-MI provides largely unbiased estimates, with a slight pessimistic bias with increasing true effect size, number of covariates and decreasing sample size. In Val-MI, accuracy of the estimate is more strongly improved by increasing the number of bootstrap draws rather than the number of imputations. With a simple integrated approach, valid confidence intervals for performance estimates can be obtained. CONCLUSIONS: When prognostic models are developed on incomplete data, Val-MI represents a valid strategy to obtain estimates of predictive performance measures.

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.

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.

Prevalence of use and level of awareness of CAM in older people - results from the KORA-Age study.

BACKGROUND: Despite the growing proportion of older adults in Europe there is only limited knowledge of CAM use among the elderly. This analysis aims to provide estimates for the prevalence of CAM use in persons with an age of ≥65, and to investigate correlations of CAM use with demographic characteristics. METHODS: Based on participants of the MONICA/KORA studies S1-S4 who were born before 1944, a random sample of 1,079 was selected for comprehensive medical examinations. Questions were presented in structured face-to-face interviews conducted from February to November 2009. RESULTS: Data on CAM use were available for 1,026 subjects with a mean age of 76 years, ranging from 65 to 93 years. 14% of the participants were unaware of CAM. The overall prevalence of CAM use was estimated 37% with minor differences between age groups, but clear differences between male (29%) and female (44%) participants. 1-year prevalence of CAM use was 22% (16% males, 28% females). 1-year of CAM use was associated with a higher level of education in both men and women; with higher income in men; and with more actual diseases in women. CONCLUSION: Findings indicate that awareness of CAM is high even among people ≥65 years. Estimates for the prevalence of CAM use confirm the relevance of this treatment sector in the healthcare system for the elderly.

Influence of external, intrinsic and individual behaviour variables on serum 25(OH)D in a German survey.

The objective of the present study was to identify external, intrinsic or behavioural factors that significantly influenced serum 25-hydroxyvitamin D (25(OH)D) concentrations in a German survey. Data from 3061 participants in the Cooperative Health Research in the Region of Augsburg, Germany (KORA) F4 survey were used to relate potential determinants to measured mean serum 25(OH)D concentrations using multivariable regression models. The factors significantly associated with hypovitaminosis D (defined as 25(OH)D<25 nmolL(-1)) were season (winter, spring and autumn), urban environment and high body mass index. In contrast, times spent in sunny regions, hours per day spent outdoors in the summer as well as additional oral intake were associated with higher 25(OH)D concentrations. These results suggest that mainly ambient UV exposure but also individual behaviour are the most important determinants for personal 25(OH)D concentrations. The analyses further showed that in winter 43% of subjects were vitamin D deficient and 42% insufficient. Even in summer over half the population has insufficient vitamin D status with 8% deficient and 47% insufficient. Therefore measures to mitigate widespread vitamin D insufficiency such as regular short-term sun exposure and/or improved dietary intake/supplementation recommendations by public health bodies need to be considered.

Treatment pattern of type 2 diabetes differs in two German regions and with patients' socioeconomic position.

BACKGROUND: Diabetes treatment may differ by region and patients' socioeconomic position. This may be particularly true for newer drugs. However, data are highly limited. METHODS: We examined pooled individual data of two population-based German studies, KORA F4 (Cooperative Health Research in the Region of Augsburg, south), and the HNR (Heinz Nixdorf Recall study, west) both carried out 2006 to 2008. To ascertain the association between region and educational level with anti-hyperglycemic medication we fitted poisson regression models with robust error variance for any and newer anti-hyperglycemic medication, adjusting for age, sex, diabetes duration, BMI, cardiovascular disease, lifestyle, and insurance status. RESULTS: The examined sample comprised 662 participants with self-reported type 2 diabetes (KORA F4: 83 women, 111 men; HNR: 183 women, 285 men). The probability to receive any anti-hyperglycemic drug as well as to be treated with newer anti-hyperglycemic drugs such as insulin analogues, thiazolidinediones, or glinides was significantly increased in southern compared to western Germany (prevalence ratio (PR); 95% CI: 1.12; 1.02-1.22, 1.52;1.10-2.11 respectively). Individuals with lower educational level tended to receive anti-hyperglycemic drugs more likely than their better educated counterparts (PR; 95% CI univariable: 1.10; 0.99-1.22; fully adjusted: 1.10; 0.98-1.23). In contrast, lower education was associated with a lower estimated probability to receive newer drugs among those with any anti-hyperglycemic drugs (PR low vs. high education: 0.66; 0.48-0.91; fully adjusted: 0.68; 0.47-0.996). CONCLUSIONS: We found regional and individual social disparities in overall and newer anti-hyperglycemic medication which were not explained by other confounders. Further research is needed.

Are diabetes risk scores useful for the prediction of cardiovascular diseases? Assessment of seven diabetes risk scores in the KORA S4/F4 cohort study.

AIM: To evaluate the utility of diabetes prediction models for CVD prediction as stated in two earlier studies. METHODS: 845 subjects from the population based German KORA (Cooperative Health Research in the Region of Augsburg) S4/F4 cohort study (aged 55 to 74 years, without diabetes, former stroke, and former myocardial infarction at baseline) were followed for up to ten years for incident stroke and myocardial infarction. Seven diabetes risk scores developed from four different studies were applied to the KORA cohort to assess their predictive ability for CVD. RESULTS: Areas under the receiver-operating curve (AROCs) for the prediction of CVD ranged from 0.60 to 0.65 when diabetes risk scores were applied to the KORA cohort. When diabetes risk scores were used to predict CVD and type 2 diabetes, respectively, AROCs for the prediction of CVD were 0.09 to 0.24 lower than AROCs for the prediction of type 2 diabetes. Furthermore, we used KORA data to develop prediction models for either diabetes or CVD, and found that they differed widely in selected predictor variables. CONCLUSION: In the older population, diabetes risk scores are not useful for the prediction of CVD, and prediction models for diabetes and CVD, respectively, require different parameters.