Gundula Behrens

Long-term pattern of brain natriuretic peptide and N-terminal pro brain natriuretic peptide and its determinants in the general population: contribution of age, gender, and cardiac and extra-cardiac factors.

The natriuretic peptides BNP and NT‐proBNP are potent cardiac markers, but knowledge of long‐term changes is sparse. We thus quantified determinants of change in BNP and NT‐proBNP in a study of south German residents (KORA).

Decline in hepatitis E virus antibody prevalence in southeastern Germany, 1996‐2011

In the past decade, an increasing frequency of acute hepatitis E was noted in Germany and other European countries. Moreover, a high prevalence (17%) of hepatitis E virus (HEV) immunoglobulin G antibodies (anti‐HEV) was recently found in the adult German population. Although this suggests an emerging pathogen, reports from other countries gave hints to a completely new aspect: a possible decrease in anti‐HEV prevalence during the last decades. To investigate the time trends of hepatitis E in southeastern Germany, we performed anti‐HEV testing in sera taken from adults in 1996 and 2011. Surplus serum specimens stored during routine operations of our diagnostic laboratory were used. The sample comprised two sets of 1,092 sera taken in 1996 and 2011, each with 182 specimens in six age groups from 20‐79 years. Testing was performed using an HEV IgG enzyme immunoassay (EIA, Axiom Diagnostics), and the recomLine HEV IgG immunoblot (Mikrogen). A significant difference in anti‐HEV prevalence was observed between the two groups: 50.7% of individuals tested positive in the 1996 group as compared to 34.3% in 2011 (EIA, P < 0.001). Results by immunoblot analysis were 20.5% (1996) versus 14.5% (2011), P < 0.001. Differences were found in all age groups and were more pronounced for the 20‐39‐year age group. Conclusion: The prevalence of anti‐HEV has decreased significantly in the past decades in southeastern Germany. The phenomenon of HEV being an emerging pathogen is thus most probably due to an increasing awareness of the disease. (Hepatology 2014;60:1180–1186)

Comparison of associations of body mass index, abdominal adiposity, and risk of colorectal cancer in a large prospective cohort study

Background: Increased body mass index (BMI) is an established colorectal cancer risk factor. High waist circumference or waist-hip-ratio (WHR) may better reflect an abnormal metabolic state and be more predictive of colorectal cancer risk than BMI. Methods: We examined BMI, waist circumference, WHR, and hip circumference in relation to colorectal cancer risk among 203,177 participants followed for 10 years. We derived standardized colorectal cancer risk estimates for each anthropometric parameter and compared predictive characteristics (Harrells C-index). In women, we examined whether hormone replacement therapy (HRT) use modified the associations between anthropometric measures and colorectal cancer. Results: We ascertained 2,869 colorectal cancers. In men, increased colon cancer risks were associated with BMI [HR per SD, 1.14; 95% confidence interval (CI), 1.08–1.20], waist circumference (HR per SD, 1.17; 95% CI, 1.08–1.27), and WHR (HR per SD, 1.09; 95% CI, 1.04–1.14). In women, anthropometric variables were unrelated to colon cancer. For men and women, anthropometric variables were unrelated to rectal cancer. Compared with BMI, waist circumference and WHR did not materially influence colon cancer prediction models [C-index changes: −0.0041 and 0.0046 (men); 0.0004 and 0.0005 (women)]. In current HRT users, colon cancer was inversely or suggestively inversely associated with waist circumference (HR per SD, 0.78; 95% CI, 0.63–0.97) and WHR (HR per SD, 0.88; 95% CI, 0.76–1.01), but positively related to hip circumference (HR per SD, 1.39; 95% CI, 1.13–1.71). Conclusion: BMI, waist circumference, and WHR show comparable positive associations with colon cancer in men. Associations between anthropometric measures and colon cancer are weak or null in women, but there is some evidence for effect modification by HRT. Impact: These findings may improve our understanding of the relation of adiposity to colorectal cancer. Cancer Epidemiol Biomarkers Prev; 22(8); 1383–94. ©2013 AACR.

Body mass index, physical activity, and risk of adult meningioma and glioma A meta-analysis

Objective: Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. Methods: We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01–1.43) and obesity (RR = 1.54, 95% CI = 1.32–1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94–1.20) and obesity (RR = 1.11, 95% CI = 0.98–1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61–0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76–0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77–1.07). Conclusions: Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma.

Physical activity in relation to risk of hematologic cancers: a systematic review and meta-analysis

Background: Despite the existence of numerous biologic pathways potentially linking increased physical activity to decreased risk of hematologic cancers, the associations between physical activity and subtype-specific hematologic cancers have not been comprehensively quantified. Methods: We conducted a systematic review and meta-analysis of physical activity in relation to subtype-specific hematologic cancers. We summarized the data from 23 eligible studies (15 cohort and eight case–control studies) and estimated summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models. Results: When comparing high versus low physical activity levels, the RR for non-Hodgkin lymphoma was 0.91 (95% CI, 0.82–1.00), for Hodgkin lymphoma it was 0.86 (95% CI, 0.58–1.26), for leukemia it was 0.97 (95% CI, 0.84–1.13), and for multiple myeloma it was 0.86 (95% CI, 0.68–1.09). When focusing on subtypes of non-Hodgkin lymphoma, the RR for diffuse large B-cell lymphoma was 0.95 (95% CI, 0.80–1.14) and for follicular lymphoma it was 1.01 (95% CI, 0.83–1.22). In an exploratory analysis combining all hematologic cancers, high versus low physical activity levels yielded a statistically significant RR of 0.93 (95% CI, 0.88–0.99). Conclusions: Physical activity showed statistically nonsignificant associations with risks of non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and leukemia. These findings may not represent a true lack of associations given the variation in high versus low physical activity definitions, the quality of physical activity assessments, and the variability in hematologic cancer classification schemes in individual studies. Impact: Physical activity is unrelated to risks of subtype-specific hematologic cancers. Cancer Epidemiol Biomarkers Prev; 23(5); 833–46. ©2014 AACR.

To stratify or not to stratify: power considerations for population-based genome-wide association studies of quantitative traits.

Meta‐analyses of genome‐wide association studies require numerous study partners to conduct pre‐defined analyses and thus simple but efficient analyses plans. Potential differences between strata (e.g. men and women) are usually ignored, but often the question arises whether stratified analyses help to unravel the genetics of a phenotype or if they unnecessarily increase the burden of analyses. To decide whether to stratify or not to stratify, we compare general analytical power computations for the overall analysis with those of stratified analyses considering quantitative trait analyses and two strata. We also relate the stratification problem to interaction modeling and exemplify theoretical considerations on obesity and renal function genetics. We demonstrate that the overall analyses have better power compared to stratified analyses as long as the signals are pronounced in both strata with consistent effect direction. Stratified analyses are advantageous in the case of signals with zero (or very small) effect in one stratum and for signals with opposite effect direction in the two strata. Applying the joint test for a main SNP effect and SNP‐stratum interaction beats both overall and stratified analyses regarding power, but involves more complex models. In summary, we recommend to employ stratified analyses or the joint test to better understand the potential of strata‐specific signals with opposite effect direction. Only after systematic genome‐wide searches for opposite effect direction loci have been conducted, we will know if such signals exist and to what extent stratified analyses can depict loci that otherwise are missed. Genet. Epidemiol. 2011.

Body size and physical activity in relation to incidence of chronic obstructive pulmonary disease

Background: Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical activity with incidence of COPD. Methods: We obtained data on anthropometric measurements and physical activity from 113 279 participants in the National Institutes of Health–AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995–1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables. Results: Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index [BMI]D≥ 35) and underweight (BMID< 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk [RR]D1.56, 95% confidence interval [CI]D1.15–2.11). Larger waist circumference (highest v. normal categories, adjusted RRD1.72, 95% CID1.37–2.16) and higher waist–hip ratio (highest v. normal categories, adjusted RRD1.46, 95% CID1.23–1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62–0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RRD0.71, 95% CID0.63–0.79) were inversely associated with COPD. Interpretation: Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD.

Multidetector computed tomography for detection and characterization of pulmonary hypertension in consideration of WHO classification.

Objective We evaluated the reliability of various multidetector computed tomography (MDCT) parameters for diagnosis and severity assessment of pulmonary hypertension (PH) with consideration of World Health Organization (WHO) classification. Methods A total of 172 patients were included in this retrospective study. One hundred fourteen patients had a diagnosis of PH (mean pulmonary artery pressure ≥25 mm Hg), and 58 patients without PH (mean pulmonary artery pressure <20 mm Hg) served as control subjects. The patients with PH were grouped according to the WHO classification based on PH etiology. Results The patients with PH had significantly greater main, left, and right pulmonary artery diameters than the control subjects (P < 0.001). No significant differences within the PH subgroups were found. Receiver operating characteristic analysis showed reasonable sensitivity and specificity for selected MDCT parameters. The severity of PH did not correlate with MDCT parameters. Conclusions Easy-to-determine MDCT parameters allow detection of PH independent of the WHO group. In patients with dilated aorta, the vertebra can be an alternative internal standard. Severity of PH cannot be estimated by MDCT parameters.

Acute Necrotizing Pancreatitis: Laboratory, Clinical, and Imaging Findings as Predictors of Patient Outcome

OBJECTIVE In patients with acute necrotizing pancreatitis, we analyzed whether laboratory and clinical findings determined in the early phase of disease and morphologic features on contrast-enhanced CT (CECT) at the beginning of the late phase of disease are helpful in predicting patient outcome and whether CECT findings provide additional information in establishing prognosis compared with the laboratory and clinical findings. MATERIALS AND METHODS A retrospective analysis of 99 patients with acute necrotizing pancreatitis was performed. Four laboratory variables (albumin, calcium, C-reactive protein, WBC count) and three clinical variables (Acute Physiology, Age, Chronic Health Evaluation [APACHE] II score; Simplified Acute Physiology Score [SAPS] II; persistent organ failure) were assessed. Five morphologic features on CECT including Balthazar grade and CT severity index were reviewed. The endpoints of patient outcome were peripancreatic or pancreatic infection, need for intervention, duration of organ failure, ICU and hospital stays, and death. Based on receiver operating characteristic curve analysis for infection, high-and low-risk groups for each prognostic variable were calculated and univariable and multivariable Cox regression analyses were carried out. RESULTS In our study population of 99 patients (63 men, 36 women; median age, 52 years; age range, 18-84 years), 25 patients (25%) developed infection, 42 patients (42%) experienced organ failure, and 12 patients (12%) died. Regarding the laboratory and clinical variables, albumin level, APACHE II score, and particularly persistent organ failure were the strongest independent predictors of patient outcome. Regarding the imaging variables, Balthazar grade and a morphologic feature that takes the distribution of intrapancreatic necrosis into account were the strongest independent predictors. In the multivariable analysis of all studied variables, imaging variables were independent and strong predictors of patient outcome and provided additional information in establishing prognosis compared with clinical and laboratory findings. CONCLUSION In patients with suspected or proven acute necrotizing pancreatitis, performing CECT at the beginning of the late phase of disease is recommended to identify patients at increased risk for adverse outcomes.

Relations of Visceral and Abdominal Subcutaneous Adipose Tissue, Body Mass Index, and Waist Circumference to Serum Concentrations of Parameters of Chronic Inflammation

Background: Different measures of body fat composition may vary in their relations to parameters of chronic inflammation. Methods: We assessed the relations of visceral (VAT) and subcutaneous adipose tissue (SAT), BMI, and waist circumference (WC) to serum concentrations of high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), resistin, and adiponectin in 97 healthy adults using multivariate linear regression models, adjusted for age, sex, smoking, physical activity, menopausal status, and use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). Parameters of chronic inflammation were mutually adjusted. Results: VAT (β = 0.34), SAT (β = 0.43), BMI (β = 0.40), and WC (β = 0.47) were all significantly associated with hs-CRP. BMI was additionally inversely related to adiponectin (β = -0.29). In exploratory subgroup analyses defined by gender, BMI, smoking, and use of aspirin or NSAIDs, VAT was the strongest indicator for increased levels of IL-6, SAT was the most consistent indicator for increased levels of hs-CRP, and BMI was the most consistent indicator for decreased levels of adiponectin. WC showed to be a weak indicator for increased levels of hs-CRP and decreased levels of adiponectin. Conclusion: VAT, SAT, BMI, and WC show distinct associations with parameters of chronic inflammation. Whether these differences reflect differential metabolic risks requires clarification by longitudinal studies.