Migraine or any headaches and white matter hyperintensities and their progression in women and men.

BACKGROUND: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. METHODS: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders. RESULTS: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. CONCLUSIONS: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

The acoustic environment before and during the SARS-CoV-2 lockdown in a major German city as measured by ecoacoustic indices.

The SARS-CoV-2 pandemic drastically changed daily life. Lockdown measures resulted in reduced traffic mobility and, subsequently, a changed acoustic environment. The exceptional lockdown was used to analyze its impact on the urban acoustic environment using ecoacoustic indices. Using data from 22 automated sound recording devices located in 9 land use categories (LUCs) in Bochum, Germany, the normalized difference soundscape index (NDSI) and Bioacoustics index (BIO) were explored. The NDSI quantifies the proportion of anthropophonic to biophonic sounds, and BIO quantifies the total sound activities of biological sources. The mean differences and standard deviation (SD) were calculated 5 weeks before and 5 weeks during the first lockdown. Pronounced peaks for the NDSI and BIO before lockdown that diminished markedly during lockdown were observed, however, with distinct differences in terms of the LUC. The mean NDSI increased from 0.00 (SD = 0.43) to 0.15 (SD = 0.50), the mean BIO decreased from 4.74 (SD = 2.64) to 4.03 (SD = 2.66). Using the NDSI and BIO together reveals that changes of the acoustic environment during lockdown are mainly driven by decreased anthropophonic sound sources. These results suggest that further studies are needed to tailor ecoacoustic indices more accurately to conditions of the urban environment.

Multilevel Conditional Autoregressive models for longitudinal and spatially referenced epidemiological data.

Multilevel Conditional Autoregressive (CAR) models help to explain the spatial effect in epidemiological studies, where subjects are nested within geographical units. This paper has two goals. Firstly, it further develops the multilevel models for longitudinal data by adding existing random effects with CAR structures that change over time. We name these models MLM tCARs. We compare the MLM tCARs to the classical multilevel growth model via simulation studies. We observe a better performance of the MLM tCARs, to retrieve the true regression coefficients and with better fit. Secondly, it provides a comprehensive decision tree for analysing data in epidemiological studies with spatially nested structure: we also consider the Multilevel CAR models (MLM CARs) for cross-sectional studies in simulation studies. We apply the models comparatively on the analysis of the association between greenness and depression in the longitudinal Heinz Nixdorf Recall Study. The results show negative association between greenness and depression.

Spatio-temporal analysis of the risk of depression at district-level and association with greenness based on the Heinz Nixdorf Recall Study.

In urban health studies where spatial and temporal changes are of importance, spatio-temporal variations are usually neglected. For the Heinz Nixdorf Recall Study, we investigate spatio-temporal variation in analyses of effects of urban greenness on depression by including spatio-temporal random effect terms in a Poisson model on district level. Our results show negative associations between greenness and depression. The findings suggest strong temporal autocorrelation and weak spatial effects. Even if the weak spatial effects are suggestive of neglecting them, as in our case, spatio-temporal random effects should be taken into account to provide reliable inference in urban health studies.

Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies.

BACKGROUND: The prevalence of olfactory impairment increases with age and is known to be an early sign of different neurodegenerative diseases. Only few population-based studies examined the prevalence of olfactory impairment and comparisons across studies are scarce. Aim of this analysis was to compare the prevalence and determinants of normosmia across five population based studies in Germany. METHODOLOGY: Data from five population-based, cross-sectional studies were included. They were independently conducted and used the same test system (Sniffin' Sticks Screening 12) to measure olfactory function. This system consists of 12 odor-dispensing felt-tip pens; the task is a forced-choice selection among four alternative odors per pen. Sociodemographic information and comorbidities were assessed in face-to-face interviews. Univariate, descriptive statistics and multivariable logistic regression models stratified by study, were performed to determine risks, i.e. prevalence odds ratios, associated with olfactory function. RESULTS: The prevalence of normosmic participants varied considerably across studies. Olfactory function was lower in men, decreased with age, and increased with higher education. Several individual comorbidities and a comorbidity index were associated with olfactory dysfunction. Recognition performance for three of the 12 pens was especially low in all studies. CONCLUSION: Four factors, well known to describe population composition, contribute to explain differences in the prevalence of olfactory function between studies when the same test system is used. Our results indicate that comorbidities and educational level should always be considered when test systems based on smell recognition are used in population-based studies.

Psoriasis, cardiovascular risk factors and metabolic disorders: sex-specific findings of a population-based study.

BACKGROUND: Scientific evidence suggests an association between psoriasis and cardiovascular and metabolic diseases. However, there are hardly any sex-specific results from population-based studies reporting the prevalence of cardiovascular risk factors in patients with psoriasis and point estimates of the association between psoriasis and cardiovascular and metabolic disorders. OBJECTIVE: Aims are to evaluate the sex-specific prevalence of psoriasis and cardiovascular risk factors, and to estimate sex-specific associations between psoriasis and diabetes type 2 (DM) and metabolic syndrome (MetS). METHODS: We used data of 3723 participants (45-75 years, 54.1% women) without coronary heart disease and missing data (psoriasis, DM, MetS) from the Heinz Nixdorf Recall study. Standardized information on health outcomes and risk factors was assessed. We performed descriptive statistics and multiple regression analyses to calculate prevalence rate ratios (PR) and 95% confidence intervals (95% CI). RESULTS: The prevalence of psoriasis was 3.8% (n = 143), with no differences between sex. We observed more often metabolic and cardiovascular risk factors in women with psoriasis compared to women without psoriasis. Interestingly, in men, this pattern was partly reversed. Multiple regression analyses revealed distinctly elevated PRs for DM for both women and men with psoriasis (fully adjusted PR: 2.43; 95% CI: 1.17-5.07, resp. 2.09; 1.16-3.76). Regarding the MetS, the results were inconsistent, showing a positive association between psoriasis and MetS in women (1.84; 1.14-2.98), but a negative association in men, even though with a wide 95% CI (0.69; 0.42-1.12). CONCLUSION: The results of our cross-sectional, population-based analysis show a distinct association between psoriasis and DM, whereas for the MetS the results contrasted between men and women, translating in women with MetS showing a higher and in men a lower chance to be psoriatic. Our results emphasize the urgent need for sex-specific research, studying the effects of psoriasis on metabolic disorders as well as effective sex tailored prevention measures.

Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study.

BACKGROUND AND AIMS: There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population. METHODS AND RESULTS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5-24.9 kg/m2) or obesity (BMI ≥30.0 kg/m2) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome - waist circumference was not taken into account because of collinearity with BMI. Persons with MHO had a higher prevalence of CAC than metabolically healthy normal weight (MHNW) persons (prevalence ratio = 1.59 (95% confidence interval 1.38-1.84) for the main analysis). Persons with MHO had slightly larger odds of CAC progression than persons with MHNW (odds ratios ranged from 1.17 (0.69-1.99) to 1.48 (1.02-2.13) depending on MHO definition and statistical approach). CONCLUSION: Our analyses on MHO CAC associations add to the evidence that MHO is not a purely benign health condition.

Association of dietary patterns with five-year degree and progression of coronary artery calcification in the Heinz Nixdorf Recall study.

BACKGROUND AND AIMS: As a modifiable lifestyle factor, diet is hypothesized to play an important role in the progression of atherosclerosis. The aim of this study was to explore associations of comprehensive dietary patterns derived by cluster analysis with degree and progression of coronary artery calcification (CAC) over five years of follow-up. METHODS AND RESULTS: In the population-based Heinz Nixdorf Recall study, 3718 participants (45-75 years; 47.6% men) without coronary heart disease completed a food frequency questionnaire at baseline. Five distinct dietary patterns were identified using cluster analysis: "Health-conscious", "Traditional German/Less alcohol", "Mediterranean-like", "Western" and "Animal fat/Alcohol" (used as reference). CAC was measured using electron-beam computed tomography at baseline and five years later. CAC after five years was predicted based on sex- and age-specific baseline percentiles. After comparing observed and predicted CAC Scores, CAC progression was classified as slow, expected, or rapid. Compared to "Animal fat/Alcohol" diet, a "Mediterranean-like" diet was associated with a relative risk (RR) for a rapid CAC progression in both sexes (men: 0.61; 95%-confidence interval [95%-CI]: 0.41; 0.90; women: 0.59; 95%-CI: 0.45; 0.78). Furthermore, reduced RRs were observed in women with a "Health-conscious" and a "Traditional German/Less alcohol" diet (0.63; 95%-CI: 0.47; 0.84, respectively 0.69; 95%-CI: 0.52; 0.90). No association was observed for a "Western" diet for both sexes. Similar results were revealed for degree of CAC. CONCLUSION: The study results support the hypothesis that a "Mediterranean-like" diet is associated with a lower CAC-progression and lower degree of CAC in men and women.

Associations between sleep characteristics and weight gain in an older population: results of the Heinz Nixdorf Recall Study.

BACKGROUND/OBJECTIVES: Sleep duration influences weight change in children and young adults, but there is less evidence in middle-aged, and, in particular, older adults. We assessed associations between sleep duration, daytime napping and sleep disturbances, respectively, with change of weight and waist circumference in older subjects. Contrary to previous studies, we also used two points in time to assess sleep characteristics. METHODS: We used data from the population-based Heinz Nixdorf Recall study, a cohort study in Germany with a baseline and two follow-up visits (age 45-74 years, median follow-up 5.1 years for first, 5.2 years for second follow-up visit). In adjusted linear regression models (N=3751), we estimated weight change between baseline and first follow-up visit in relation to various self-reported sleep characteristics measured at baseline. Furthermore, we estimated change of weight and waist circumference, respectively, between first and second follow-up visit in relation to patterns of sleep characteristics measured at baseline and at the first follow-up visit (N=2837). RESULTS: In all analyses, short and long sleep duration, sleep disturbances, and regular daytime napping were associated with <1 kg of weight gain and <1 cm of gain in waist circumference over 5 years compared with the respective reference categories. For example, compared with 7-<8 h night sleep, short night sleep (⩽5 h at baseline) was associated with 0.5 kg of weight gain (95% confidence interval: -0.1; 1.1 kg). CONCLUSIONS: Our study gave no evidence that sleep characteristics were associated with clinically relevant weight gain in the older population.

Direct costs in impaired glucose regulation: results from the population-based Heinz Nixdorf Recall study.

OBJECTIVE: For the first time, this population-based study sought to analyze healthcare utilization and associated costs in people with normal fasting glycemia (NFG), impaired fasting glycemia (IFG), as well as previously undetected diabetes and previously diagnosed diabetes linking data from the prospective German Heinz Nixdorf Recall (HNR) study with individual claims data from German statutory health insurances. RESEARCH DESIGN AND METHODS: A total of 1709 participants of the HNR 5-year follow-up (mean age (SD) 64.9 (7.5) years, 44.5% men) were included in the study. Age-standardized and sex-standardized healthcare utilization and associated costs (reported as € for the year 2008, perspective of the statutory health insurance) were stratified by diabetes stage defined by the participants' self-report and fasting plasma glucose values. Cost ratios (CRs) were estimated using two-part regression models, adjusting for age, sex, sociodemographic variables and comorbidity. RESULTS: The mean total direct healthcare costs for previously diagnosed diabetes, previously undetected diabetes, IFG, and NFG were €2761 (95% CI 2378 to 3268), €2210 (1483 to 4279), €2035 (1732 to 2486) and €1810 (1634 to 2035), respectively. Corresponding age-adjusted and sex-adjusted CRs were 1.53 (1.30 to 1.80), 1.16 (0.91 to 1.47), and 1.09 (0.95 to 1.25) (reference: NFG). Inpatient, outpatient and medication costs varied in order between people with IFG and those with previously undetected diabetes. CONCLUSIONS: The study provides claims-based detailed cost data in well-defined glucose metabolism subgroups. CRs of individuals with IFG and previously undetected diabetes were surprisingly low. Data are important for the model-based evaluation of screening programs and interventions that are aimed either to prevent diabetes onset or to improve diabetes therapy as well.

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

[Conflicting Rules and Incentives for Health Promotion and Prevention in the German Statutory Health Insurance (GKV)]. / Normen- und Anreizkonflikte für die gesetzlichen Krankenkassen in Gesundheitsförderung und Prävention.

OBJECTIVES: This study examines what role the German statutory health insurance (GKV) has in health promotion and prevention, if regulations and incentives are consistent, and if the politically-intended strengthening of prevention has been achieved. METHODS: We compiled the regulations and incentives of the German Sozialgesetzbuch V as the legal basis for health promotion and prevention of the GKV and studied their effects and interactions. Using annual financial reports of GKV we determined how the spending in prevention overall and in specific fields of prevention has -developed. RESULTS: The responsibilities of the GKV in health promotion and prevention lack a clear scientific foundation. Regulations have been incrementally added following changing ideas in prevention and health promotion policies. Currently, different norms and a variety of incentives lead to inconsistent and conflicting aims. Only 2% of all expenditures of the GKV are for health promotion and prevention, mainly spent for medical measures like preventive medical check-ups or vaccination. While spending of the GKV in general is rising, expenditures for prevention have decreased since 2009. CONCLUSIONS: There is a need to harmonise the different regulations in health promotion and prevention and to correct currently inconsistent incentives in the GKV. Given the similar evidence base there seems to be no reason why responsibilities for health promotion and primary, secondary or tertiary prevention should be regulated by different normative constructs. Incentives should account for the different aims of health insurers and their members. Financial incentives to increase spending in prevention may be particularly effective when there is no short-term -financial interest for the health insurer.

Association of neighbourhood unemployment rate with incident Type 2 diabetes mellitus in five German regions.

AIM: To analyse the association of neighbourhood unemployment with incident self-reported physician-diagnosed Type 2 diabetes in a population aged 45-74 years from five German regions. METHODS: Study participants were linked via their addresses at baseline to particular neighbourhoods. Individual-level data from five population-based studies were pooled and combined with contextual data on neighbourhood unemployment. Type 2 diabetes was assessed according to a self-reported physician diagnosis of diabetes. We estimated proportional hazard models (Weibull distribution) in order to obtain hazard ratios and 95% CIs of Type 2 diabetes mellitus, taking into account interval-censoring and clustering. RESULTS: We included 7250 participants residing in 228 inner city neighbourhoods in five German regions in our analysis. The incidence rate was 12.6 per 1000 person-years (95% CI 11.4-13.8). The risk of Type 2 diabetes mellitus was higher in men [hazard ratio 1.79 (95% CI 1.47-2.18)] than in women and higher in people with a low education level [hazard ratio 1.55 (95% CI 1.18-2.02)] than in those with a high education level. Independently of individual-level characteristics, we found a higher risk of Type 2 diabetes mellitus in neighbourhoods with high levels of unemployment [quintile 5; hazard ratio 1.72 (95% CI 1.23-2.42)] than in neighbourhoods with low unemployment (quintile 1). CONCLUSIONS: Low education level and high neighbourhood unemployment were independently associated with an elevated risk of Type 2 diabetes mellitus. Studies examining the impact of the residential environment on Type 2 diabetes mellitus will provide knowledge that is essential for the identification of high-risk populations.

Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification.

BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.

Percentile distribution of blood pressure readings in 35683 men and women aged 18 to 99 years.

The percentile distribution of blood pressure (BP) with regard to age, sex and cardiovascular risk factors is unknown. We aimed to provide epidemiological data for a comprehensive description of the BP distribution across a wide age-range. We used data from the German Metabolic and Cardiovascular Risk Project (GEMCAS), a cross-sectional study with 35 683 participants aged 18-99 years, conducted during October 2005 in 1511 randomly selected general practices in Germany. BP and waist circumference were measured, data on lifestyle, cardiovascular disease (CVD) risk factors and medication assessed. In men, we found even in the lowest percentile (5th) a gradual increase of the systolic BP from the lowest to the highest age group of 10 mm Hg, all other percentile groups an increase of 20 mm Hg. In women, this increase ranged from 15 mm Hg (5th percentile) to 40 mm Hg (95th percentile). In a subgroup of participants with no antihypertensive usage (n=22 550) and no CVD/CVD risk factors (n=13 297), we still observed a distinct age-related increase of BP readings. Our study provides detailed information on the population distribution of BP readings in both sexes and also among very old individuals. The results are useful in a public health context to plan gender- and age-specific prevention strategies.

Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222.

BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(-24), minor allele frequency ~0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.

Cardiac risk in patients with treatment naïve, first-line medically controlled and first-line surgically cured acromegaly in comparison to matched data from the general population.

INTRODUCTION: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS). DESIGN: Retrospective comparative matched case-control study. PATIENTS & METHODS: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated. RESULTS: Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls. CONCLUSION: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery.

Duplications in RB1CC1 are associated with schizophrenia; identification in large European sample sets.

Schizophrenia (SCZ) is a severe and debilitating neuropsychiatric disorder with an estimated heritability of ~80%. Recently, de novo mutations, identified by next-generation sequencing (NGS) technology, have been suggested to contribute to the risk of developing SCZ. Although these studies show an overall excess of de novo mutations among patients compared with controls, it is not easy to pinpoint specific genes hit by de novo mutations as actually involved in the disease process. Importantly, support for a specific gene can be provided by the identification of additional alterations in several independent patients. We took advantage of existing genome-wide single-nucleotide polymorphism data sets to screen for deletions or duplications (copy number variations, CNVs) in genes previously implicated by NGS studies. Our approach was based on the observation that CNVs constitute part of the mutational spectrum in many human disease-associated genes. In a discovery step, we investigated whether CNVs in 55 candidate genes, suggested from NGS studies, were more frequent among 1637 patients compared with 1627 controls. Duplications in RB1CC1 were overrepresented among patients. This finding was followed-up in large, independent European sample sets. In the combined analysis, totaling 8461 patients and 112 871 controls, duplications in RB1CC1 were found to be associated with SCZ (P=1.29 × 10(-5); odds ratio=8.58). Our study provides evidence for rare duplications in RB1CC1 as a risk factor for SCZ.

The impact of regional deprivation and individual socio-economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population-based studies.

AIM: Our objective was to test the hypothesis that the prevalence of Type 2 diabetes increases with increasing regional deprivation even after controlling for individual socio-economic status. METHODS: We pooled cross-sectional data from five German population-based studies. The data set contained information on n = 11,688 study participants (men 50.1%) aged 45-74 years, of whom 1008 people had prevalent Type 2 diabetes (men 56.2%). Logistic multilevel regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes prevalence. We controlled for sex, age and lifestyle risk factors, individual socio-economic status and regional deprivation, based on a new small-area deprivation measure, the German Index of Multiple Deprivation. RESULTS: Adjusted for sex, age, body mass index (BMI), physical activity, smoking status and alcohol consumption, the prevalence of Type 2 diabetes showed a stepwise increase in risk with increasing area deprivation [OR 1.88 (95% CI 1.16-3.04) in quintile 4 and OR 2.14 (95% CI 1.29-3.55) in quintile 5 compared with the least deprived quintile 1], even after controlling for individual socio-economic status. Focusing on individual socio-economic status alone, the risk of having diabetes was significantly higher for low compared with medium or high educational level [OR 1.46 (95% CI 1.24-1.71)] and for the lowest compared with the highest income group [OR 1.53 (95% CI 1.18-1.99)]. CONCLUSION: Regional deprivation plays a significant part in the explanation of diabetes prevalence in Germany independently of individual socio-economic status. The results of the present study could help to target public health measures in deprived regions.