The Alcohol Harm Paradox in Periodontitis.

Individuals of lower socioeconomic position (SEP) experience a greater rate of alcohol-related harms, yet they consume equal or lower amounts of alcohol than higher-SEP individuals. This phenomenon, called the "alcohol harm paradox" (AHP), gained attention recently, and different mechanisms have been proposed to explain it. Since both SEP and alcohol have been suggested to be associated with periodontitis risk, we conducted a secondary analysis using data from the National Health and Nutrition Examination Survey 2011 to 2012 and 2013 to 2014 cycles, aiming to examine 1) whether the association between alcohol consumption and periodontitis is modified by SEP and 2) the extent to which the effect of SEP inequalities on periodontitis is mediated by and/or interacts with alcohol consumption. We set educational attainment as the main SEP proxy and tested the poverty income ratio in subsequent sensitivity analyses. Effect measure modification analysis was employed, considering heavy drinking as exposure, and causal mediation analysis based on the potential outcome's framework decomposed the effect of SEP on periodontitis in proportions attributable to mediation and interaction. Models were fitted using binary logistic regression and adjusted for sex, ethnicity, age, body mass index, smoking status, diabetes, binge drinking, and regular preventive dental visits. The analytical sample comprised 4,057 participants. After adjusting for covariates, less educated heavy drinkers presented 175% (odds ratio, 2.75; 95% confidence interval [CI], 2.04-3.72) higher odds of periodontitis than their counterparts, and super-additive associations were found (relative excess risk due to interaction: 1.35; 95% CI, 0.49-2.20). Additionally, -69.5% (95% CI, -122.1% to -16.8%) of the effects of education on periodontitis were attributable to interaction with heavy drinking, consistent with the AHP. No contribution was found for the mechanism of mediation. Heavy drinking disproportionately impacts the occurrence of periodontitis in lower-SEP individuals. Lower-SEP individuals seem to experience differential effects of heavy drinking on periodontitis.

Sjögren's Disease and Oral Health: A Genetic Instrumental Variable Analysis.

Epidemiological studies have consistently shown that Sjögren's disease (SjD) increases the risk of dental caries. Despite similar evidence indicating an elevated risk of periodontitis, SjD remains a disputed risk factor for this disease. The risk of bias in observational research is a major impediment to confirming this link. Within an instrumental variable framework, genetic variants associated with a risk factor can be used to proxy its effect on an outcome while avoiding common sources of observational study bias. In this study, we leveraged an instrumental variable approach to investigate whether SjD affects the risk of caries and periodontitis. A total of 57 genetic variants strongly associated with SjD were identified from a genome-wide association study of 2,247 European descent cases and 332,115 controls. We tested for associations of these genetic instruments with caries (measured as the number of decayed, missing, and filled surfaces in 26,792 individuals) and periodontitis (17,353 clinical periodontitis cases and 28,210 European controls). Several sensitivity analyses were used to further validate the primary inverse variance weighted (IVW) estimate. IVW analysis revealed an adverse effect of SjD on caries (ß = 0.039, P = 6.3e-16) and periodontitis (odds ratio = 1.033, P = 2.3e-05). Sensitivity analyses, conducted to assess the robustness to potential violations of instrumental variable assumptions, further support these findings. Our results showed that SjD has a detrimental effect on caries and also suggest that SjD promotes periodontitis.

Frequency and risk factors of post-intensive care syndrome components in a multicenter randomized controlled trial of German sepsis survivors.

BACKGROUND: Post-intensive care syndrome (PICS) is a combination of cognitive, psychiatric and physical impairments in survivors of critical illness and intensive care. There is little data on long-term co-occurrence of associated impairments. METHODS: Analysis of data from 289 sepsis survivors from a German multicenter RCT. Impairments associated with PICS (depression, PTSD, cognitive impairment, chronic pain, neuropathic symptoms, dysphagia) during 24 months follow-up are used to explore the frequency and risk factors of PICS components in three classification models. RESULTS: The majority of participants showed impairments in 2-3 of 6 domains during follow-up. The overall frequency of PICS according to the classification models ranged from 32.9% to 98.6%. In regression analyses, there were no significant effects in selected ICU-related exposures or covariates for PICS classification models. Regarding individual components, only higher age and longer duration of ICU treatment and mechanical ventilation showed significant positive associations with the occurrence of cognitive impairment during follow-up, as did male gender and higher age for dysphagia. CONCLUSIONS: Almost all study participants showed impairments associated with PICS in at least one domain. The proposed classification models for PICS appear to be too broad to identify specific risk factors beyond its individual components.

Relationship between atopic dermatitis, depression and anxiety: a two-sample Mendelian randomization study.

BACKGROUND: Growing evidence suggests that atopic dermatitis (AD) is associated with an increased risk of depressive disorders and anxiety. However, existing studies were observational and may have uncovered correlations but could not easily disentangle noncausal or reverse-causal associations because these associations could be confounded and may not reflect true causal relationships. OBJECTIVES: To examine, in a two-sample Mendelian randomization study, the potential effect of AD on the risk of depressive disorders and anxiety. METHODS: Genetic instruments from the largest available genome-wide association study (GWAS) for AD (10 788 cases and 30 047 controls) were used to investigate the relationship to broad depression (170 756 cases and 329 443 controls), major depressive disorder (MDD; 30 603 cases and 143 916 controls) and anxiety (5580 cases and 11 730 controls). A set of complementary approaches were carried out to assess horizontal pleiotropy and related potential caveats occurring in MR studies. RESULTS: We observed no causal impact of AD on the risk of depressive disorders and anxiety, with close-to-zero effect estimates. The inverse weighted method revealed no associations of AD on broad depression [odds ratio (OR) 1·014; P = 0·431], probable MDD (OR 1·002; P = 0·568), International Classification of Diseases, Ninth/Tenth Revision-based MDD (OR 1·001; P = 0·466) or anxiety (OR 1·097; P = 0·180). CONCLUSIONS: This MR study does not support a causal effect of AD on depression and anxiety.

Area-level and individual correlates of active transportation among adults in Germany: A population-based multilevel study.

This study aimed at estimating the prevalence in adults of complying with the aerobic physical activity (PA) recommendation through transportation-related walking and cycling. Furthermore, potential determinants of transportation-related PA recommendation compliance were investigated. 10,872 men and 13,144 women aged 18 years or older participated in the cross-sectional 'German Health Update 2014/15 - EHIS' in Germany. Transportation-related walking and cycling were assessed using the European Health Interview Survey-Physical Activity Questionnaire. Three outcome indicators were constructed: walking, cycling, and total active transportation (≥600 metabolic equivalent, MET-min/week). Associations were analyzed using multilevel regression analysis. Forty-two percent of men and 39% of women achieved ≥600 MET-min/week with total active transportation. The corresponding percentages for walking were 27% and 28% and for cycling 17% and 13%, respectively. Higher population density, older age, lower income, higher work-related and leisure-time PA, not being obese, and better self-perceived health were positively associated with transportation-related walking and cycling and total active transportation among both men and women. The promotion of walking and cycling among inactive people has great potential to increase PA in the general adult population and to comply with PA recommendations. Several correlates of active transportation were identified which should be considered when planning public health policies and interventions.

Suicidality and risk of suicidality in psoriasis: a critical appraisal of two systematic reviews and meta-analyses.

AIM: Chi et al.1 and Singh et al.2 each conducted a systematic review and meta-analysis of observational studies examining the relationship between suicidality and psoriasis. SETTING AND DESIGN: Chi et al. included only cohort studies while Singh et al. included cohort, cross-sectional and case-control studies. PRIMARY EXPOSURE AND OUTCOME: The primary outcome, suicidality, was assessed in people with psoriasis (exposure) and people without psoriasis. Analyses were separated for suicidal ideation and behaviour. RESULTS: Chi et al. included five population-based cohort studies that were considered to be of high quality according to the Newcastle-Ottawa Scale (NOS). They found no significant increase in the risk of suicide [risk ratio (RR) 1·13, 95% confidence interval (CI) 0·87-1·46], suicide attempt (RR 1·25, 95% CI 0·89-1·75) or suicidality (RR 1·26, 95% CI 0·97-1·64) among people with psoriasis. Singh et al. included 18 studies that were rated to be of medium quality to high quality according to the NOS. They found a pooled odds ratio (OR) of 2·05 (95% CI 1·54-2·74) for suicidal ideation among patients with psoriasis. For suicidal behaviours (combined attempted and completed suicides) a pooled OR of 1·26 (95% CI 1·13-1·40) was obtained, suggesting a higher risk of these behaviours in people with psoriasis. Subgroup analysis showed that patients with psoriasis were more likely to attempt suicide (OR 1·32, 95% CI 1·14-1·54) and complete suicide (OR 1·20, 95% CI 1·04-1·39) than those without psoriasis. CONCLUSIONS: Singh et al. concluded that patients with psoriasis have a significantly higher risk of suicidal ideation, suicide attempts and completed suicides, while Chi et al. concluded that the available, limited, very low-quality evidence does not support the notion of an association between psoriasis on the one hand, and suicide, suicidal ideation and suicide attempts on the other.

12-year changes in cardiovascular risk factors in people with major depressive or bipolar disorder: a prospective cohort analysis in Germany.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder are associated with certain cardiovascular risk factors (CVRFs), but it is unclear whether they are associated with unfavourable changes of clinically manifest CVRFs over time. METHODS: We used baseline and 12-year follow-up (n = 1887) data from the German Health Interview and Examination Survey 1998. Multivariable linear regression models assessed associations between lifetime CIDI-diagnosed mood disorders at baseline and continuous risk factor-related outcomes (blood pressure, HbA1c, LDL-C, HDL-C, triglycerides, BMI) at follow-up. RESULTS: We did not find consistent deterioration of CVRFs in persons with compared to persons without MDD. Analyses pointed to severity of mood disorder as an important correlate of long-term changes of comorbid hypertension: while a history of mild MDD was not associated with changes in CVRFs, moderate MDD was associated with lower blood pressure [systolic: ß = - 7.5 (CI - 13.2; - 1.9); diastolic: ß = - 4.5 (CI - 7.8; - 1.3)] and a history of bipolar disorder was associated with higher systolic blood pressure at follow-up (ß = 14.6; CI 4.9-24.4). Further, severe MDD was weakly associated with a higher BMI at follow-up [ß = 1.2 (CI 0.0; 2.4)]. These outcomes were not mediated by use of psychotropic medication and remained statistically significant after adjusting for the use of antihypertensive medication. CONCLUSION: Since most investigated parameters showed no associations, participants with a lifetime history of MDD in this cohort did not carry a specific risk for a worsening of pre-existing clinically manifest CVRFs. Our findings extend evidence of MDD severity and bipolar disorder as important correlates of long-term changes of arterial hypertension and obesity.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Vitamin D and health care costs: Results from two independent population-based cohort studies.

BACKGROUND & AIMS: Vitamin D deficiency is associated with higher morbidity. However, there is few data regarding the effect of vitamin D deficiency on health care costs. This study examined the cross-sectional and longitudinal associations between the serum 25-hydroxy vitamin D concentration (25OHD) and direct health care costs and hospitalization in two independent samples of the general population in North-Eastern Germany. METHODS: We studied 7217 healthy individuals from the 'Study of Health in Pomerania' (SHIP n = 3203) and the 'Study of Health in Pomerania-Trend' (SHIP-Trend n = 4014) who had valid 25OHD measurements and provided data on annual total costs, outpatient costs, hospital stays, and inpatient costs. The associations between 25OHD concentrations (modelled continuously using factional polynomials) and health care costs were examined using a generalized linear model with gamma distribution and a log link. Poisson regression models were used to estimate relative risks of hospitalization. RESULTS: In cross-sectional analysis of SHIP-Trend, non-linear associations between the 25OHD concentration and inpatient costs and hospitalization were detected: participants with 25OHD concentrations of 5, 10 and 15 ng/ml had 226.1%, 51.5% and 14.1%, respectively, higher inpatient costs than those with 25OHD concentrations of 20 ng/ml (overall p-value = 0.001) in multivariable models. CONCLUSIONS: We found a relation between lower 25OHD concentrations and increased inpatient health care costs and hospitalization. Our results thus indicate an influence of vitamin D deficiency on health care costs in the general population.

Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP).

BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p < 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.

Approval of psychotherapy and medication for the treatment of mental disorders over the lifespan. An age period cohort analysis.

AIMS: Previous cross-sectional studies revealed inconsistent results regarding mental health treatment preferences among the general population. In particular, it is unclear to what extent specific age groups approve psychotherapy or psychotropic medication for the treatment of mental disorders. We explore whether treatment recommendations of either psychotherapy or psychiatric medication change over the lifespan which includes age-related effects due to increasing age of a person, cohort effects that reflect specific opinions during the time a person was born and period effects that reflect societal changes. METHODS: Using data from three identical population surveys in Germany from 1990, 2001 and 2011 (combined n = 9046), we performed age-period-cohort analyses to determine the pure age, birth cohort and time period effects associated with the specific treatment recommendations for a person with either depression or schizophrenia, using logistic Partial Least-Squares regression models. RESULTS: For both disorders, approval of both psychotherapy and medication for a person with mental illness increases with age. At the same time, younger cohorts showed stronger recommendations particularly for psychotherapy (OR around 1.07 per decade). The strongest effects could be observed for time period with an increase in recommendation between 1990 and 2001 with odds ratio of 2.36 in depression and 2.97 in schizophrenia, respectively. In general, the treatment option that showed the strongest increase in recommendation was medication for schizophrenia and psychotherapy for depression. CONCLUSION: Underutilisation of psychotherapy in old age seems not to reflect treatment preferences of older persons. Thus, special treatment approaches need to be offered for this group that seems to be willing for psychotherapy but do not yet use it. Cohort patterns suggest that approval of psychotherapy among older persons will likely further increase in the coming years as these people get older. Finally, strong period effects underpin the importance of changing attitudes in the society. These could reflect reporting changes about psychiatric topics in the media or a general increase in the perception of treatment options. Nevertheless, more treatment offers especially for older people are needed.

An online intervention using information on the mental health-mental illness continuum to reduce stigma.

BACKGROUND: A core component of stigma is being set apart as a distinct, dichotomously different kind of person. We examine whether information on a continuum from mental health to mental illness reduces stigma. METHOD: Online survey experiment in a quota sample matching the German population for age, gender and region (n=1679). Participants randomly received information on either (1) a continuum, (2) a strict dichotomy of mental health and mental illness, or (3) no information. We elicited continuity beliefs and stigma toward a person with schizophrenia or depression. RESULTS: The continuum intervention decreased perceived difference by 0.19 standard deviations (SD, P<0.001) and increased social acceptance by 0.18 SD (P=0.003) compared to the no-text condition. These effects were partially mediated by continuity beliefs (proportion mediated, 25% and 26%), which increased by 0.19 SD (P<0.001). The dichotomy intervention, in turn, decreased continuity beliefs and increased notions of difference, but did not affect social acceptance. CONCLUSION: Attitudes towards a person with mental illness can be improved by providing information on a mental health-mental illness continuum.

Trends of barriers to eye care among adults with diagnosed diabetes in Germany, 1997-2012.

BACKGROUND AND AIMS: To study trends of barriers to receiving recommended eye care among subjects with diabetes aged 20-81 years in northeast Germany. METHODS AND RESULTS: We analyzed population-based data from two repeated cross-sectional surveys conducted in 1997-2001 and 2008-2012 (Ns of 4308 and 4402). Andersen's Behavioral Model of Health Services Utilization was used to identify individual-level demographic, financial and health-related barriers to annual eye-care utilization in subjects with a self-reported physician's diabetes and to examine population trends in these barriers. The prevalence of diabetes increased from 6.5% to 11.4%. The prevalence of annual eye-care utilization among persons with diabetes decreased from 69.4% to 56.0% (adjusted relative risk = 0.77, p < 0.001). The decline of eye care utilization over the past decade in eye-care use was more pronounced in groups at risk for diabetes-related complications (i.e., lower socio-economic status, >5 years since diagnosis of diabetes, poor glycemic control, obesity, smoking, lack of physical activity, co-existing diseases). We identified relevant predictors of missed annual eye-care use among diabetics. CONCLUSION: The increase of diabetes prevalence and downward trend of eye-care visits at the recommended level call for development, implementation and evaluation of continued efforts to improve access to eye specialists, particularly among those with poor diabetic control, co-existing diabetic complications, and comorbidities.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

[Integration of primary and secondary data in the Study of Health in Pomerania and description of clinical outcomes using stroke as an example]. / Die Integration von Primär- und Sekundärdaten in der Study of Health in Pomerania und die Beschreibung von klinischen Endpunkten am Beispiel Schlaganfall.

OBJECTIVE: This study describes (i) the procedure of obtaining patients' consent for secondary data usage, (ii) the complexity of integrating data from multiple sources, and (iii) the correspondence among patients' self-reports, physician reports, routine data, hospital discharge diagnosis, and cause-of-death coding regarding stroke. METHODS: Data from the first follow-up (N=3 186) of the population-based Study of Health in Pomerania (SHIP) were used. These data were combined with secondary data from the Greifswald University Hospital, the association of statutory health insurance physicians Mecklenburg-Western Pomerania, physician reports, and death certificates. RESULTS: Consent for using health-related information from all data sources in question was obtained from more than 90% of the SHIP participants. Follow-up data from at least one source were available for 2 747 (86%) participants. For 92 participants information about the occurrence of stroke was found in at least one data source. In 59 cases the event appeared in only one data source, in 24 cases the event was found in 2 sources, and for 9 participants 3 data sources reported on the event. CONCLUSION: Participants of a population-based cohort are highly willing to give consent for using their health-related information from secondary data sources. Yet, data integration is challenging due to considerable differences in data type, structure and coverage.

Do attitudes towards persons with mental illness worsen during the course of life? An age-period-cohort analysis.

OBJECTIVE: Cross-sectional studies frequently find higher age associated with negative attitudes towards persons with mental illness. We explore whether attitudes worsen over the life span, or follow a cohort pattern. METHOD: Using data from three identical population surveys in Germany from 1990, 2001 and 2011 (combined sample n = 7835), we performed age-period-cohort analyses determining the association of age, time period and birth-cohort with social distance from a person with either depression (n = 3910) or schizophrenia (n = 3925), using linear and nonlinear partial least squares regression models. RESULTS: Social distance increases with age, independent from cohort and period effects, cumulating to an increase of 2.4 (schizophrenia) and 2.3 (depression) on the 28 point social distance scale over the life span (youngest to oldest participant). We found a cohort effect in depression, but not schizophrenia, with decreasing social distance until 1970 and a slight increase in younger cohorts. Period effects were visible particularly in schizophrenia, with growing social distance over time. CONCLUSION: Considering demographic change and the vulnerability of older persons to severe outcomes of mental illness such as suicide, the observed increase of negative attitudes over the life span seems highly relevant. We discuss the role of conservatism and preferences for agreeable social contacts in older age.

The combined effects of alcohol consumption and body mass index on hepatic steatosis in a general population sample of European men and women.

BACKGROUND: Research on the association between alcohol consumption and hepatic steatosis revealed conflictive results. AIM: To investigate the associations between average daily alcohol consumption and binge drinking with hepatic steatosis, and to analyse combined effects of average daily alcohol consumption and binge drinking with body mass index (BMI) on hepatic steatosis. METHODS: Data from the population-based Study of Health in Pomerania (SHIP) conducted in north-east Germany comprising 4009 adults were used. Alcohol consumption was assessed by self-report. Serum carbohydrate-deficient transferrin (CDT) was analysed as biomarker for alcohol consumption. Hepatic steatosis was diagnosed by ultrasonography. RESULTS: Analyses revealed a dose-response relationship between average daily alcohol consumption and hepatic steatosis in men starting with a consumption of 20 g of alcohol per day [adjusted odds ratio (OR) compared to abstainers 1.53; 95% confidence interval (CI) 1.15-2.05]. Using CDT as alternative exposure variable confirmed these results. Binge drinking was associated with hepatic steatosis in men (adjusted OR of binge drinkers compared to nonbinge drinkers 1.36, 95% CI 1.06-1.74). The likelihood of having hepatic steatosis increased in men and women with increasing levels of average daily alcohol consumption in combination with overweight or obesity. Similarly, binge drinking in combination with overweight or obesity enhanced the likelihood of having hepatic steatosis. CONCLUSIONS: Overweight or obesity substantially enhanced the effect of high levels of average daily alcohol consumption and binge drinking on hepatic steatosis in the present study population. This finding underlines the necessity to screen for multiple risk factors in the prevention of hepatic steatosis.

Long-term changes in body weight are associated with changes in blood pressure levels.

BACKGROUND AND AIMS: Hypertension and obesity are highly prevalent in Western societies. We investigated the associations of changes in body weight with changes in blood pressure and with incident hypertension, incident cardiovascular events, or incident normalization of blood pressure in patients who were hypertensive at baseline, over a 5-year period. METHODS AND RESULTS: Data of men and women aged 20-81 years of the Study of Health in Pomerania were used. Changes in body weight were related to changes in blood pressure by linear regression (n = 1875) adjusted for cofounders. Incident hypertension, incident cardiovascular events, or incident blood pressure normalization in patients who were hypertensive at baseline were investigated using Poisson regression (n = 3280) models. A change of 1 kg in body weight was positively associated with a change of 0.45 mm Hg (95% confidence interval (CI): 0.34-0.55 mm Hg) in systolic blood pressure, 0.32 mm Hg (95% CI: 0.25-0.38 mm Hg) in diastolic blood pressure, and 0.36 mm Hg (95% CI: 0.29-0.43 mm Hg) in mean arterial pressure (all p-values <0.001). A 5% weight loss reduced the relative risk (RR) of incident hypertension (RRs 0.84 (95% CI: 0.79-0.89)) and incident cardiovascular events (RRs 0.81 (95% CI: 0.68-0.98)) and increased the chance of incident blood pressure normalization in patients who were hypertensive at baseline by 15% (95% CI: 7-23%). CONCLUSIONS: Absolute and relative changes in body weight are positively associated with changes in blood pressure levels and also affect the risk of cardiovascular events.

Osteocalcin is associated with testosterone in the general population and selected patients with bone disorders.

Research in the last decade has revealed that bone is not only a target tissue for numerous circulating hormones but functions as an endocrine organ itself. As a recent study demonstrated a stimulatory effect of the osteoblast-derived hormone osteocalcin (OCN) on testosterone production in mice, we investigated whether such an association can be replicated in humans. We used data from 1338 men (25-86 years) in the population-based epidemiological Study of Health in Pomerania and from 110 male outpatients with bone disorders (18-85 years) for the study. We analysed cross-sectional associations between OCN and total testosterone serum concentrations (TT), as well as associations between further markers of bone turnover [bone-specific alkaline phosphatase (BAP), serum C-terminal telopeptides of Type I collagen (CTX), urinary deoxypyridinoline] and TT using ordinary least square (OLS) regression models. Multivariable OLS models revealed a positive association between OCN and TT in the population-based (ß coefficients for a one standard deviation increase, 0.590; standard error (SE), 0.175; p-value, <0.01) and patient-based (ß coefficient, 0.575; SE, 0.132; p-value, <0.01) samples even after adjustment for age and body mass index (both samples), and time of blood sampling (population-based sample only). Furthermore, we observed positive associations between BAP and TT (ß coefficient, 0.403; SE, 0.170; p-value, 0.02) as well as between CTX and TT (ß coefficient, 0.733; SE, 0.172; p-value, <0.01) in men from the general population. The present investigation shows that OCN is associated with TT in the general population and in patients with bone disorders, and may thus indicate general male health status. Additional longitudinal observational studies are warranted to confirm our findings and future experimental research is necessary to elucidate potential mechanisms underlying the observed associations.

Mendelian randomization suggests non-causal associations of testosterone with cardiometabolic risk factors and mortality.

Prospective studies showed that low serum testosterone concentrations are associated with various cardiometabolic risk factors and mortality. However, the causal nature of these associations is controversial. We studied 1 882 men aged 20-79 years with serum testosterone concentrations and genotyping data from the longitudinal population-based Study of Health in Pomerania. Testosterone concentrations were cross-sectionally associated with cardiometabolic risk factors, including anthropometric, lipid, blood pressure and glycaemic parameters; and prospectively with all-cause mortality (277 deaths, 14.7%) during the 10-year follow-up. To overcome problems of residual confounding, reverse causation, or regression dilution bias in the investigated testosterone-outcome associations, we used two-stage least square regression models with previously identified polymorphisms at the SHBG gene (rs12150660) and X chromosome (rs5934505) as multiple genetic instruments in an instrumental variable (IV) approach, also known as Mendelian randomization. In standard regression analyses, testosterone was robustly associated with a wide range of cardiometabolic risk factors. In subsequent IV analyses, no such significant associations were observed. Similarly, prospective analyses showed a consistent association of low testosterone concentrations with increased all-cause mortality risk, which was not apparent in subsequent IV analyses. The present Mendelian randomization analyses did not detect any evidence for causal associations of testosterone concentrations with cardiometabolic risk factors and mortality, suggesting that previously reported associations might largely result from residual confounding or reverse causation. Although testosterone assessment might improve risk prediction, implementation of testosterone replacement therapy requires further evidence of a direct effect on cardiometabolic outcomes from double-blinded randomized controlled trials and large-scale Mendelian randomization meta-analyses.