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101. Informed Consent in GANI_MED—A Sectional Design for Clinical Epidemiological Studies Within Individualized Medicine

Author

Pia Erdmann, Wenke Liedtke, Roberto Lorbeer, Martin Langanke, and Jakob Fasold

Subjects
Identification (information), Research ethics, medicine.medical_specialty, business.industry, Informed consent, Family medicine, Epidemiology, Alternative medicine, Medicine, Normative, Personalized medicine, business, Omics
Abstract

Clinical epidemiological research is an important approach within Individualized Medicine. This research allows for the identification of possible biomarkers for specific diseases through the use of data from clinical treatments. From a research ethical point of view it needs to be noted that respective studies are mostly very complex. Therefore a variety of different normative requirements of both ethical and legal natures need to be met. On the one hand those studies aim for the scientific use of clinical records. On the other hand samples of biomaterial are to be collected, stored and analyzed using -omics methods. Sometimes there are also study examinations included in these studies which may produce incidental findings.

Published
2015

102. Thoracic and abdominal aortic diameters in a general population: MRI-based reference values and association with age and cardiovascular risk factors

Author

Birger Mensel, Roberto Lorbeer, Marcus Dörr, Henry Völzke, Lydia Heßelbarth, Jens-Peter Kühn, Wolfgang Lieb, Katrin Hegenscheid, and Michael Wenzel

Subjects
Adult, Male, medicine.medical_specialty, Aging, Cross-sectional study, Body Surface Area, Population, Aorta, Thoracic, Blood Pressure, 030204 cardiovascular system & hematology, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Risk Factors, medicine.artery, medicine, Thoracic aorta, Humans, Radiology, Nuclear Medicine and imaging, Aorta, Abdominal, education, Neuroradiology, Aged, Body surface area, education.field_of_study, medicine.diagnostic_test, business.industry, Cholesterol, HDL, Smoking, Interventional radiology, Magnetic resonance imaging, General Medicine, Middle Aged, Healthy Volunteers, Cross-Sectional Studies, Cardiovascular Diseases, Linear Models, Female, Radiology, business, Magnetic Resonance Angiography
Abstract

To generate reference values for thoracic and abdominal aortic diameters determined by magnetic resonance imaging (MRI) and analyse their association with cardiovascular risk factors in the general population.Data from participants (n = 1759) of the Study of Health in Pomerania were used for analysis in this study. MRI measurement of thoracic and abdominal aortic diameters was performed. Parameters for calculation of reference values according to age and sex analysis were provided. Multivariable linear regression models were used for determination of aortic diameter-related risk factors, including smoking, blood pressure (BP), high-density lipoprotein cholesterol (HDL-C).For the ascending aorta (β = -0.049, p 0.001), the aortic arch (β = -0.061, p 0.001) and the subphrenic aorta (β = -0.018, p = 0.004), the body surface area (BSA)-adjusted diameters were lower in men. Multivariable-adjusted models revealed significant increases in BSA-adjusted diameters with age for all six aortic segments (p 0.001). Consistent results for all segments were observed for the positive associations of diastolic BP (β = 0.001; 0.004) and HDL (β = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (β = -0.001).Some BSA-adjusted median aortic diameters are smaller in men than in women. All diameters increase with age, diastolic blood pressure and HDL-C and decrease as systolic BP increases.• Median aortic diameter increases with age and diastolic blood pressure. • Median aortic diameter is larger in men than in women. • Some BSA-adjusted median aortic diameters are smaller in men than in women.

Published
2014

103. Pancreatic fat content by magnetic resonance imaging in subjects with prediabetes, diabetes, and controls from a general population without cardiovascular disease

Author

Sigrid Auweter, Jürgen Machann, Holger Hetterich, Christopher L. Schlett, Fabian Bamberg, Sophia D. Heber, Konstantin Nikolaou, Maximilian F. Reiser, Christian Bayerl, Roberto Lorbeer, Corinna Storz, and Annette Peters

Subjects
Male, lcsh:Medicine, Adipose tissue, Comorbidity, Biochemistry, Gastroenterology, Diagnostic Radiology, 030218 nuclear medicine & medical imaging, Fats, Endocrinology, 0302 clinical medicine, Glucose Metabolism, Risk Factors, Medicine and Health Sciences, Prediabetes, lcsh:Science, education.field_of_study, Univariate analysis, Alcohol Consumption, Multidisciplinary, medicine.diagnostic_test, Radiology and Imaging, Middle Aged, Lipids, Magnetic Resonance Imaging, Adipose Tissue, Cardiovascular Diseases, Population Surveillance, Cohort, Carbohydrate Metabolism, Female, Anatomy, Research Article, medicine.medical_specialty, Endocrine Disorders, Imaging Techniques, Population, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Research and Analysis Methods, Prediabetic State, 03 medical and health sciences, Diagnostic Medicine, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, education, Pancreas, Nutrition, Aged, business.industry, lcsh:R, Case-control study, Biology and Life Sciences, Magnetic resonance imaging, medicine.disease, Diet, Metabolism, Biological Tissue, Metabolic Disorders, Case-Control Studies, lcsh:Q, business, Biomarkers
Abstract

Background/Objective Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population. Methods Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic fat content was quantified by measuring the proton-density fat fraction (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by placing ROIs in the pancreatic head, body, and tail by independent readers. In addition, hepatic fat content as well as abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses were employed to determine associations. Results A total of 385 subjects were included in the analysis (median age: 57 years, 58.2% males), of them 53 were classified as subjects with diabetes, 95 as prediabetes, and 237 as controls (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3±9.4], and significantly higher in subjects with prediabetes and diabetes as compared to controls (PDFFpanc: 6.2% [IQR: 3.5±12] vs. 8.6% [IQR: 4.3±17.5] vs. 4.9% [3.1±7.4], p0.12). While in univariate analysis BMI, PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p

Published
2017

104. Serum Thyrotropin Concentrations Are Not Associated with the Ankle-Brachial Index: Results from Three Population-Based Studies

Author

Stephan B. Felix, Daniel Tiller, Karin Halina Greiser, Karl Werdan, Josef Köhrle, Till Ittermann, Marcus Dörr, Ina Lehmphul, Roberto Lorbeer, Alexander Kluttig, and Henry Völzke

Subjects
endocrine system, medicine.medical_specialty, Pathology, education.field_of_study, Clinical Thyroidology / Original Paper, endocrine system diseases, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, Thyroid, Population, Reference range, Endocrinology, medicine.anatomical_structure, Internal medicine, Immunoassay, Epidemiology, medicine, Ankle, Thyroid function, business, education, Hormone
Abstract

Background: There is only limited data on the potential association between thyroid dysfunction and peripheral arterial disease (PAD). Objective: The aim of our study was to investigate the potential association of thyroid function, as defined by serum concentrations of the clinically used primary thyroid function marker thyrotropin [i.e. thyroid-stimulating hormone (TSH)] and 3,5-diiodothyronine (3,5-T2), with the ankle-brachial index (ABI) as a marker of PAD. Methods: We used data from 5,818 individuals from three cross-sectional population-based studies conducted in Northeast (SHIP-2 and SHIP-TREND) and Central Germany (CARLA). Measurement of serum TSH concentrations was conducted in one central laboratory for all three studies. In a randomly selected subpopulation of 750 individuals of SHIP-TREND, serum 3,5-T2 concentrations were measured with a recently developed immunoassay. ABI was measured either by a hand-held Doppler ultrasound using the Huntleigh Dopplex D900 or palpatorily by the OMRON HEM-705CP device. Results: Serum TSH concentrations were not significantly associated with ABI values in any of the three studies. Likewise, groups of individuals with a TSH

Published
2014

105. Cardiovascular risk factors and thoracic aortic wall thickness in a general population

Author

Jens-Peter Kühn, Katrin Hegenscheid, Birger Mensel, Alexander Quadrat, Marcus Dörr, Tobias Schneider, Henry Völzke, Roberto Lorbeer, and Wolfgang Lieb

Subjects
Adult, Male, medicine.medical_specialty, Population, Aorta, Thoracic, Body Mass Index, Young Adult, Sex Factors, Risk Factors, Internal medicine, medicine.artery, Medicine, Thoracic aorta, Humans, Radiology, Nuclear Medicine and imaging, Myocardial infarction, education, Triglycerides, Aged, Aged, 80 and over, education.field_of_study, business.industry, Smoking, Age Factors, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Hemoglobin A, Blood pressure, Cardiovascular Diseases, Study of Health in Pomerania, Descending aorta, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract

To evaluate the association of cardiovascular risk factors with wall thickness of the ascending and descending thoracic aorta in the general population.The study included 1,176 individuals (523 women) 21-83 years old from the Study of Health in Pomerania without history of stroke or myocardial infarction. Aortic wall thickness (AWT) was determined by cine magnetic resonance imaging. The associations of AWT with the cardiovascular risk factors male sex, age, smoking, body mass index (BMI), systolic and diastolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were assessed by multivariable linear regression models, and interaction effects were tested.Male sex (β = .086, P.001), age (β = .006, P.001), and BMI (β = .013, P.001) were positively associated with the AWT of the ascending aorta. Male sex (β = .105, P.001), age (β = .006, P.001), current smoker (β = .044, P = .010), BMI (β = .013, P.001), and HDL-C (β = .057, P = .008) revealed a positive association with AWT of the descending aorta. LDL-C (β = -.024, P = .009; β = -.018, P = .010) was inversely associated with the AWT of the ascending and descending aorta, respectively. Triglyceride levels (β = .024, P = .027; β = .018, P = .024) showed a positive association with the AWT of the ascending and descending aorta, respectively, in men, but not in women.Established cardiovascular risk factors, including male sex, older age, smoking, high BMI, and high triglyceride levels, were associated with increasing thoracic AWT of the ascending and descending aorta. High HDL-C and low LDL-C levels were correlated with AWT.

Published
2014

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

Author

Till Ittermann, Henry Völzke, P. Troitzsch, Rainer Rettig, Sabine Schipf, Henri Wallaschofski, N. Aumannn, Marcello Ricardo Paulista Markus, Marcus Dörr, Sebastian E. Baumeister, and Roberto Lorbeer

Subjects
Adult, Male, medicine.medical_specialty, Mean arterial pressure, Time Factors, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Blood Pressure, Prehypertension, Body Mass Index, symbols.namesake, Young Adult, Risk Factors, Internal medicine, Linear regression, Weight Loss, medicine, Humans, Poisson regression, Longitudinal Studies, skin and connective tissue diseases, Life Style, Aged, Aged, 80 and over, Nutrition and Dietetics, business.industry, Incidence, Middle Aged, medicine.disease, Obesity, Confidence interval, Endocrinology, Blood pressure, Study of Health in Pomerania, Hypertension, symbols, Cardiology, Linear Models, Female, sense organs, Waist Circumference, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

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.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-values0.001). 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%).Absolute and relative changes in body weight are positively associated with changes in blood pressure levels and also affect the risk of cardiovascular events.

Published
2014

108. Cell specific eQTL analysis without sorting cells

Author

Cisca Wijmenga, Albert Hofman, Andrew B. Singleton, Michael Roden, Thomas Meitinger, Mathieu Platteel, Katharina Schramm, Claudia Schurmann, Roberto Lorbeer, Christian Herder, Seiko Makino, Julian C. Knight, Harm-Jan Westra, Lude Franke, Anis Larbi, Veikko Salomaa, Marijn C. Visschedijk, Dena G. Hernandez, Konstantin Strauch, Holger Prokisch, Lili Milani, Fernando Rivadeneira, Francesca Zolezzi, Joyce B. J. van Meurs, Marjolein J. Peters, Samuli Ripatti, Leonard H. van den Berg, Jan H. Veldink, Markus Perola, André G. Uitterlinden, Rinse K. Weersma, Danny Arends, Pärt Peterson, Timouthy M. Frayling, Bernett Lee, David Melzer, Olaf Rötzschke, Anand Kumar Andiappan, Michael Poidinger, Yang Li, Andres Metspalu, Andrew R. Wood, Juha Karjalainen, Tõnu Esko, Harald Grallert, Uwe Völker, Luigi Ferrucci, Eva Reinmaa, Astrid Petersmann, De Yun Wang, Benjamin P. Fairfax, Jingyuan Fu, Georg Homuth, Liina Tserel, Rossella Melchiotti, Hanieh Yaghootkar, Ritsert C. Jansen, Silva Kasela, and Johannes Kettunen

Subjects
Cell specific, 0303 health sciences, Cell type, Sorting, Single-nucleotide polymorphism, Computational biology, Biology, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Expression quantitative trait loci, 030212 general & internal medicine, Whole Organism, 030304 developmental biology, Whole blood
Abstract

Expression quantitative trait locus (eQTL) mapping on tissue, organ or whole organism data can detect associations that are generic across cell types. We describe a new method to focus upon specific cell types without first needing to sort cells. We applied the method to whole blood data from 5,683 samples and demonstrate that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils.

Published
2014

109. Cohort profile: Greifswald approach to individualized medicine (GANI_MED)

Author

Uwe Lendeckel, Marcus Dörr, Vivian Werner, Kathleen Klein, Werner Siegmund, Beate Fiene, Rainer Rettig, Roberto Lorbeer, Nele Friedrich, Wolfgang Lieb, Matthias Schwab, Markus M. Lerch, Nicole Endlich, Jana Kuhn, Holger Kock, Wolfgang Rathmann, Pia Erdmann, Sylvia Stracke, Karlhans Endlich, Michael Hecker, Marek Zygmunt, Stephan B. Felix, Manuela Gesell Salazar, Julia Mayerle, Wolfgang Hoffmann, Hans J. Grabe, Konrad Meissner, Andrea Schulz, Konrad Ott, Henriette E. Meyer zu Schwabedissen, Henri Wallaschofski, Tim Kacprowski, Janina Krafczyk, Martin Langanke, Claudia Richardt, Christoph Havemann, Henry Völzke, Heinrich Assel, Matthias Nauck, Thomas Bahls, Tobias Fischer, Elke Hammer, Robin Haring, Uwe Völker, Heyo K. Kroemer, Karsten Suhre, Thomas Kocher, Ulf Schminke, Mariacarla Gadebusch-Bondio, Saskia Ungerer, Ralf Ewert, Marius Ueffing, Steffen Flessa, Karen Saljé, and Birte Holtfreter

Subjects
medicine.medical_specialty, Epidemiology, Genomic data, Alternative medicine, Diagnostic tools, Time based, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Metabolic Diseases, medicine, Protocol, Humans, Medical physics, ddc:610, Precision Medicine, Medicine(all), business.industry, Biochemistry, Genetics and Molecular Biology(all), Optimal treatment, Personalized Medicine, General Medicine, Individualized Medicine, therapy [Cardiovascular Diseases], 3. Good health, therapy [Metabolic Diseases], Cardiovascular Diseases, Family medicine, Cohort, Personalized medicine, business, Biomarkers, Cohort study, metabolism [Biomarkers]
Abstract

Background Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the “Greifswald Approach to Individualized Medicine” (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice. Methods/design Clinical patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular diseases are being established following a standardized protocol for the assessment of medical history, laboratory biomarkers, and the collection of various biosamples for bio-banking purposes. A multi-omics based biomarker assessment including genome-wide genotyping, transcriptome, metabolome, and proteome analyses complements the multi-level approach of GANI_MED. Comparisons with the general background population as characterized by our Study of Health in Pomerania (SHIP) are performed. A central data management structure has been implemented to capture and integrate all relevant clinical data for research purposes. Ethical research projects on informed consent procedures, reporting of incidental findings, and economic evaluations were launched in parallel. peerReviewed

Published
2014

110. Periodontitis Is Associated with Endothelial Dysfunction in a General Population: A Cross-Sectional Study

Author

Roberto Lorbeer, Ralf Ewert, Thomas Kocher, Henry Völzke, Sven Gläser, Klaus Empen, Marcus Dörr, and Birte Holtfreter

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Brachial Artery, Cross-sectional study, Science, Population, Internal medicine, Medicine, Humans, Endothelial dysfunction, education, Periodontitis, Aged, Aged, 80 and over, Inflammation, education.field_of_study, Multidisciplinary, business.industry, Middle Aged, medicine.disease, Cross-Sectional Studies, Clinical attachment loss, Cardiovascular Diseases, Study of Health in Pomerania, Population study, Female, Endothelium, Vascular, business, Cohort study, Research Article, Follow-Up Studies
Abstract

A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend)=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p

Published
2013

111. MRI-based determination of reference values of thoracic aortic wall thickness in a general population

Author

Marcus Dörr, Katrin Hegenscheid, Roberto Lorbeer, Wolfgang Lieb, Henry Völzke, Jens-Peter Kühn, Birger Mensel, Alexander Quadrat, and Tobias Schneider

Subjects
Adult, Male, medicine.medical_specialty, Population, Aortic Diseases, Magnetic Resonance Imaging, Cine, Young Adult, Reference Values, Risk Factors, medicine.artery, Internal medicine, Germany, Ascending aorta, medicine, Prevalence, Thoracic aorta, Humans, Radiology, Nuclear Medicine and imaging, education, Aorta, Aged, Aged, 80 and over, education.field_of_study, business.industry, Ultrasound, General Medicine, Middle Aged, Atherosclerosis, Aortic wall, Thoracic aortic wall, Cross-Sectional Studies, Descending aorta, Reference values, Population Surveillance, cardiovascular system, Cardiology, Female, Radiology, business
Abstract

To provide age- and sex-specific reference values for MRI-derived wall thickness of the ascending and descending aorta in the general population. Data of 753 subjects (311 females) aged 21-81 years were analysed. MRI was used to determine the aortic wall thickness (AWT). Equations for reference value calculation according to age were established for females and males. Median wall thickness of the ascending aorta was 1.46 mm (5th–95th range: 1.15–1.88 mm) for females and 1.56 mm (1.22-1.99 mm) for males. Median wall thickness of the descending aorta was 1.26 mm (0.97-1.58 mm) in females and 1.36 mm (1.04-1.75 mm) in males. While median and 5th and 95th percentiles for the ascending and descending aorta increased with age in both sexes, the association between age and median AWT was stronger in males than in females for both the ascending and descending aorta. Reference values for the ascending and descending AWT are provided. In a healthy sample from the general population, the wall of the ascending aorta is thicker than the wall of the descending aorta, and both walls are thicker in males than females. The increase in wall thickness with age is greater in males. • Ascending aortic wall thickness is greater than descending aortic wall thickness. • Ascending and descending aortic wall thickness is greater in males. • Thoracic aortic wall thickness increases with age in both sexes. • The age-related increase in aortic wall thickness is stronger in males.

Published
2013

112. Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population

Author

Anne Grotevendt, Roberto Lorbeer, Sebastian E. Baumeister, Henri Wallaschofski, Henry Völzke, Marcus Dörr, M. Nauck, Ramachandran S. Vasan, and Wolfgang Lieb

Subjects
Male, medicine.medical_specialty, Population, Statistics as Topic, Gastroenterology, Angiopoietin-2, Risk Factors, Internal medicine, Germany, Neoplasms, medicine, Humans, Receptor, education, Cardiovascular mortality, Proportional Hazards Models, education.field_of_study, business.industry, Angiopoietin 2, Hazard ratio, Middle Aged, medicine.disease, Receptor, TIE-2, Confidence interval, Net reclassification improvement, Standardized mortality ratio, Cardiovascular Diseases, Heart failure, Study of Health in Pomerania, Population Surveillance, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Aims To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample. Methods and results Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI) 1.19–1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18–1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89–1.32; P = 0.416). Levels of sTie-2 were not significantly related to all-cause mortality (HR 1.12; 95% CI 0.98–1.27; P = 0.102). Adding Ang-2 to a prediction model for all-cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, −0.015; P = 0.571). Conclusion In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a mortality prediction model only modestly improved discrimination.

Published
2013

113. The Global Cardiovascular Risk Transition: Associations of Four Metabolic Risk Factors with Macroeconomic Variables in 1980 and 2008

Author

Goodarz, Danaei, Gitanjali, M Singh, Christopher, J Paciorek, John, K Lin, Melanie, J Cowan, Mariel, M Finucane, Farshad, Farzadfar, Gretchen, A Stevens, Leanne, M Riley, Yuan, Lu, Mayuree, Rao, Majid, Ezzati, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group: Writing and Global Analysis Group: Goodarz Danaei, Paciorek, Christopher J., Lin, John K., Cowan, Melanie J., Finucane, Mariel M., Stevens, Gretchen A., Riley, Leanne M., Peres, Cynthia Pérez, Román Pérez-Fernández, Rafael Pichardo, Hwee Pin Phua, Majid Ezzati. Contributed equally to the research and manuscript and listed in alphabetic order. Country Data Group: Geir Aamodt, Ziad Abdeen, Nabila A. Abdella, Hanan F. Abdul Rahim, Juliet Addo, Wichai Aekplakorn, Mustafa M. Afifi, Enrico Agabiti-Rosei, Carlos A. Aguilar Salinas, Charles Agyemang, Mohamed M. Ali, Mohannad Al-Nsour, Abdul R. Al-Nuaim, Ramachandran Ambady, Pertti Aro, Fereidoun Azizi, Carlo M. Barbagallo, Marco Antonio M. Barbieri, Alberto Barceló, Sandhi M. Barreto, Henrique Barros, Leonelo E. Bautista, Athanase Benetos, Peter Bjerregaard, Cecilia Björkelund, Simona Bo, Martin Bobak, Enzo Bonora, Babu V. Bontha, Manuel A. Botana, Pascal Bovet, Juergen Breckenkamp, Monique M. Breteler, Grazyna Broda, Ian J. Brown, Michael Bursztyn, Antonio Cabrera de León, Hannia Campos, Francesco P. Cappuccio, Vincenzo Capuano, Edoardo Casiglia, Maurizio Castellano, Katia Castetbon, Luis Cea, ChihJen Chang, Noureddine Chaouki, Somnath Chatterji, Chien-Jen Chen, Zhengming Chen, Jin-Su Choi, Lily Chua, Renata Cífková, Linda J. Cobiac, Richard S. Cooper, Anna Maria Corsi, Michael C. Costanza, Cora L. Craig, Rachel S. Dankner, Saeed Dastgiri, Elias Delgado, Gonul Dinc, Yasufumi Doi, Guang-Hui Dong, Eleonora Dorsi, Nico Dragano, Adam Drewnowski, Robert W. Eggertsen, Paul Elliott, Anders Engeland, Cihangir Erem, Alireza Esteghamati, Caroline H. D. Fall, Jian-Gao Fan, Catterina Ferreccio, Leopold Fezeu, Josélia O. Firmo, Hermes J. Florez, Nélida S. Fornés, F. Gerry R. Fowkes, Guido Franceschini, Fredrik Frisk, Flávio D. Fuchs, Eva L. Fuller, Linn Getz, Simona Giampaoli, Luis F. Gómez, Juan M. Gomez-Zumaquero, Sidsel Graff-Iversen, Janet F. Grant, Ramiro Guerrero Carvajal, Martin C. Gulliford, Rajeev Gupta, Prakash C. Gupta, Oye Gureje, Tine W. Hansen, Jun Hata, Jiang He, Noor Heim, Joachim Heinrich, Tomas Hemmingsson, Anselm Hennis, William H. Herman, Victor M. Herrera, Suzanne Ho, Michelle Holdsworth, Gunilla Hollman Frisman, Wilma M. Hopman, Akhtar Hussain, Abdullatif Husseini, M. Mohsen Ibrahim, Nayu Ikeda, Bjarne K. Jacobsen, Hashem Y. Jaddou, Tazeen H. Jafar, Mohsen Janghorbani, Grazyna Jasienska, Michel R. Joffres, Jost B. Jonas, Othman A. Kadiki, Ofra Kalter-Leibovici, Raoul M. Kamadjeu, Ioannis Karalis, Mika J. Kastarinen, Joanne Katz, Lital Keinan-Boker, Paul Kelly, Omid Khalilzadeh, Young-Ho Khang, Stefan Kiechl, Ki Woong Kim, Yutaka Kiyohara, Junji Kobayashi, Maressa P. Krause, Růžena Kubínová, Pawel Kurjata, Yadlapalli S. Kusuma, Tai Hing Lam, Arnulf Langhammer, Carlene M. M. Lawes, Cai Le, Jeannette Lee, Claire Lévy-Marchal, Yanping Li, Yuqiu Li, Stephen Lim, T. O. Lim, Xu Lin, Cheng-Chieh Lin, Hsien-Ho Lin, Lars Lind, Lauren Lissner, Xiaoqing Liu, Patricio Lopez-Jaramillo, Roberto Lorbeer, Guansheng Ma, Stefan Ma, Francesc Macià, David R. MacLean, Stefania Maggi, Dianna J. Magliano, Marcia Makdisse, Giuseppe Mancia, Toshifumi Mannami, Pedro Marques-Vidal, Jean Claude N. Mbanya, Norma McFarlane-Anderson, Roberto Miccoli, Juhani Miettola, Hoang V. Minh, Juan F. Miquel, J. Jaime Miranda, Mostafa K. Mohamed, V. Mohan, Salim Mohanna, Ali Mokdad, Willem F. Mollentze, Dante D. Morales, Karen Morgan, Lorenza M. Muiesan, Sergio Muntoni, Iraj Nabipour, Tomoko Nakagami, Vinay Nangia, Barbara Nemesure, Martin Neovius, Kjersti A. Nerhus, Flavio Nervi, Hannelore Neuhauser, Minh Nguyen, Toshiharu Ninomiya, Marianna Noale, Sang W. Oh, Takayoshi Ohkubo, Oliviero Olivieri, Ayse Emel Önal, Altan Onat, Myriam Oróstegui, Hermann Ouedraogo, Wen-Harn Pan, Demosthenes B. Panagiotakos, Francesco Panza, Yongsoo Park, Valeria M. A. Passos, Mangesh S. Pednekar, Marco A., Pistelli, Francesco, Pedro Plans, Maria Polakowska, Neil Poulter, Dorairaj Prabhakaran, Qing Qiao, Masoud Rafiei, Olli, T. Raitakari, Luiz R. Ramos, Sanjay Rampal, Lekhraj Rampal, Finn Rasmussen, Kanala K. R. Reddy, Josep Redon, Luis Revilla, Victoria Reyes-García, Ragab B. Roaeid, Fernando Rodriguez-Artalejo, Rosalba Rojas-Martinez, Kimmo Ronkainen, Luis Rosero-Bixby, Gregory A. Roth, Harshpal S. Sachdev, José R. Sánchez, Selim Y. Sanisoglu, Susana Sans, Nizal Sarraf-Zadegan, Marcia Scazufca, Beatriz D. Schaan, Norberto Schapochnik, Hedi Schelleman, Ione J. C. Schneider, C. Mary Schooling, Bernhard Schwarz, Cevad Sekuri, Martha S. Sereday, Lluís Serra-Majem, Jonathan Shaw, Abdul S. Shera, Zumin Shi, Rahman Shiri, Xiao Ou Shu, Diego Augusto Santos Silva, Eglé Silva, Leon A. Simons, Margaret Smith, Stefan Söderberg, Suharko Soebardi, Vincenzo Solfrizzi, Emily Sonestedt, Ahmet Soysal, Pär Stattin, Aryeh D. Stein, George S. Stergiou, Jochanan Stessman, Akihiro Sudo, Machi Suka, Valter Sundh, Kristina Sundquist, Johan Sundström, Andrew B. Swai, E. Shyong Tai, Kristian Tambs, Fikru Tesfaye, George N. Thomas, Margaret Thorogood, Reijo S. Tilvis, Martin Tobias, Liv E. Torheim, Peter Trenkwalder, Jaakko O. Tuomilehto, Josep A. Tur, Christophe Tzourio, Ana I. Uhernik, Flora A. Ukoli, Nigel Unwin, Stephen Vander Hoorn, Mark P. Vanderpump, Jose Javier Varo, Marit B. Veierød, Gustavo Velásquez-Meléndez, Monique Verschuren, Lucie Viet, Salvador Villalpando, Jesus Vioque, Peter Vollenweider, Stefano Volpato, Ningli Wang, Ya X. Wang, Mark Ward, Sarwono Waspadji, Lennart X. Welin, Lars Wilhelmsen, Johann Willeit, Mark Woodward, André J. Xavier, Fei Xu, Liang Xu, Akira Yamamoto, Gonghuan Yang, Xiaoguang Yang, Li-Chia Yeh, Jin-Sang Yoon, Qisheng You, Zhijie Yu, Jian Zhang, Lei Zhang, Wei Zheng, and Maigeng Zhou.

Subjects
obesity, diabetes mellitus, blood pressure, cholesterol, epidemiology
Published
2013

114. National, regional, and global trends in adult overweight and obesity prevalences

Author

Stevens, G. A., Singh, G. M., Lu, Y., Danaei, G., Lin, J. K., Finucane, M. M., Bahalim, A. N., Mcintire, R. K., Gutierrez, H. R., Cowan, M., Paciorek, C. J., Farzadfar, F., Riley, L., Ezzati, M., for the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index): Geir Aamodt, Ziad, Abdeen, Nabila, A Abdella, Hanan, F Abdul-Rahim, Juliet, Addo, Mohamed, M Ali, Mohannad, Al-Nsour, Ramachandran, Ambady, Pertti, Aro, Carlo, M Barbagallo, Alberto, Barceló, Henrique, Barros, Leonelo, E Bautista, Peter, Bjerregaard, Enzo, Bonora, Pascal, Bovet, Grazyna, Broda, Ian, J Brown, Michael, Bursztyn, Antonio Cabrera de León, Francesco, P Cappuccio, Katia, Castetbon, Somnath, Chatterji, Zhengming, Chen, Chien-Jen, Chen, Lily, Chua, Renata, Cífková, Linda, J Cobiac, Anna Maria Corsi, Cora, L Craig, Saeed, Dastgiri, Martha, S de Sereday, Gonul, Dinc, Yasufumi, Doi, Eleonora, Dorsi, Nico, Dragano, Adam, Drewnowski, Paul, Elliott, Anders, Engeland, Alireza, Esteghamati, Jian-Gao, Fan, Catterina, Ferreccio, Nélida, S Fornés, Flávio, D Fuchs, Simona, Giampaoli, Sidsel, Graffiversen, Janet, F Grant, Ramiro Guerrero Carvajal, Martin, C Gulliford, Rajeev, Gupta, Prakash, C Gupta, Oye, Gureje, Noor, Heim, Joachim, Heinrich, Tomas, Hemmingsson, Victor, M Herrera, Suzanne, C Ho, Michelle, Holdsworth, Wilma, M Hopman, Abdullatif, Husseini, Nayu, Ikeda, Bjarne, K Jacobsen, Tazeen, H Jafar, Mohsen, Janghorbani, Grazyna, Jasienska, Michel, R Joffres, Jost, B Jonas, Ofra, Kalter-Leibovici, Ioannis, Karalis, Joanne, Katz, Lital, Keinan-Boker, Paul, Kelly, Omid, Khalilzadeh, Young-Ho, Khang, Stefan, Kiechl, Maressa, P Krause, Yadlapalli, S Kusuma, Arnulf, Langhammer, Jeannette, Lee, Claire, Lévy-Marchal, Yanping, Li, Yuqiu, Li, Stephen, Lim, Cheng-Chieh, Lin, Lauren, Lissner, Patricio, Lopez-Jaramillo, Roberto, Lorbeer, Guansheng, Ma, Stefan, Ma, Francesc, Macià, Dianna, J Magliano, Marcia, Makdisse, Miccoli, Roberto, Juhani, Miettola, Jaime, Miranda, Mostafa, K Mohamed, Mohan, V, Salim, Mohanna, Ali, Mokdad, Dante, D Morales, Lorenza, M Muiesan, Iraj, Nabipour, Vinay, Nangia, Barbara, Nemesure, Martin, Neovius, Kjersti, A Nerhus, Flavio, Nervi, Hannelore, Neuhauser, Minh, Nguyen, Ayse, E Önal, Altan, Onat, Myriam, Orostegui, Hermann, Ouedraogo, Demosthenes, B Panagiotakos, Francesco, Panza, Yongsoo, Park, Mangesh, S Pednekar, Marco, A Peres, Rafael, Pichardo, Hwee Pin Phua, Pistelli, Francesco, Pedro, Plans, Dorairaj, Prabhakaran, Roaeid, B Ragab, Olli, T Raitkari, Sanjay, Rampal, Finn, Rasmussen, Josep, Redon, Luis, Revilla, Victoria, Reyes-García, Fernando, Rodriguez-Artalejo, Luis, Rosero-Bixby, Harshpal, S Sachdev, José, R Sánchez, Selim, Y Sanisoglu, Norberto, Schapochnik, Lluís, Serra-Majem, Rahman, Shiri, Xiao Ou Shu, Leon, A Simons, Margaret, Smith, Vincenzo, Solfrizzi, Emily, Sonestedt, Pär, Stattin, Aryeh, D Stein, George, S Stergiou, Jochanan, Stessman, Akihiro, Sudo, Valter, Sundh, Kristina, Sundquist, Johan, Sundström, Martin, Tobias, Liv, E Torheim, Josep, A Tur, Ana, I Uhernik, Flora, A Ukoli, Mark, P Vanderpump, Jose Javier Varo, Marit, B Veierød, Gustavo, Velásquez-Meléndez, Monique, Verschuren, Salvador, Villalpando, Jesus, Vioque, Peter, Vollenweider, Mark, Ward, Sarwono, Waspadji, Johann, Willeit, Mark, Woodward, Liang, Xu, Fei, Xu, Gonghuan, Yang, Li-Chia, Yeh, Jinsang, Yoon, Qisheng, You, Wei, Zheng., Stevens, G, Singh, G, Lu, Y, Danaei, G, Lin, J, Finucane, M, Bahalim, A, McIntire, R, Gutierrez, H, Cowan, M, Paciorek, C, Farzadfar, F, Riley, L, Ezzati, M, and Barbagallo, CM

Subjects
medicine.medical_specialty, Pediatrics, Settore MED/09 - Medicina Interna, Overweight, Obesity, Prevalence, Population health, Risk transition, Global health, Noncommunicable diseases, Epidemiology, Global health, Population health, Overweight, lcsh:Computer applications to medicine. Medical informatics, Obesity, Prevalence, Risk transition, Noncommunicable diseases, Medicine, obesity, overweight, business.industry, Research, Public health, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Sciences bio-médicales et agricoles, medicine.disease, lcsh:R858-859.7, medicine.symptom, business, Male obesity, Body mass index, Demography
Abstract

0, info:eu-repo/semantics/published

Published
2012

115. Abdominal Aortic Aneurysm Is Associated with a Variant in Low-Density Lipoprotein Receptor-Related Protein 1

Author

Wolfgang Lieb, Bruna Gigante, Thodur M. Vasudevan, Georg Homuth, Joseph B. Muhlestein, Mark J. Daly, Andrew P. Morris, Jacqueline de Graaf, Peter Kraft, Ann-Kristin Petersen, André G. Uitterlinden, Jaqueline C M Witteman, Valgerdur Steinthorsdottir, Jutta Palmen, Amanda L. Elliott, Cecilia M. Lindgren, Richard N. Bergman, Benjamin D. Horne, Tony R. Merriman, Robert W. Davies, Jaspal S. Kooner, Gavin Lucas, Carl G. P. Platou, Diederick E. Grobbee, Ruth J. F. Loos, Fulvio Ricceri, Karin Leander, Wen H. L. Kao, Torsten Lauritzen, Qi Sun, Narisu Narisu, Stephan B. Felix, N. William Rayner, Aaron R. Folsom, Robert D. Sayers, Ross D. Blair, John F. Carlquist, Jing Hua Zhao, L. Vicky Phillips, Gabe Crawford, Anne Johnson, Chris Wallace, Paul F. O'Reilly, Jose C. Florez, Andreas Ziegler, Salvatore Panico, Neil R. Robertson, Ruth Frikke-Schmidt, Leif Groop, Pier Mannuccio Mannucci, Stanley L. Hazen, Gerjan Navis, Peter P. Pramstaller, Laura J. Scott, Niels Grarup, Klaus Berger, Christian Gieger, Stephen E. Epstein, Cornelia Huth, Stephanie Tennstedt, Morris J. Brown, Timothy A. Barnes, Naomi Hammond, Ulf de Faire, Vilmundur Gudnason, Marcus Fischer, Nita G. Forouhi, Paolo Vineis, Thomas Quertermous, Christopher Patterson, W.H. Wilson Tang, Konstantinos A. Papadakis, Lincoln Stein, Maciej Tomaszewski, Suthesh Sivapalaratnam, M. S. Sandhu, Feng Zhang, Christa Meisinger, David R. Lewis, Norman Klopp, Roza Blagieva, Gonçalo R. Abecasis, Jeffrey L. Anderson, Lu Qi, Amy J. Swift, Albert Hofman, George Dedoussis, Robert Luben, Daniel J. Rader, Thomas Münzel, Bert Bravenboer, Christopher J. O'Donnell, Elin Org, Veikko Salomaa, Philipp S. Wild, Stephen G. Ellis, Dawn M. Waterworth, Vesela Gateva, Loukianos S. Rallidis, Joseph M. Devaney, kevin Burnand, Robert Clarke, George A. Wells, Harold Snieder, Kay-Tee Khaw, Panos Deloukas, Jaakko Tuomilehto, Louise V. Wain, Eric Boerwinkle, Inke R. König, Amanda J. Bennett, Uwe Völker, Florian Ernst, Markus M. Nöthen, Thomas Sparsø, Jean Tichet, Inga Prokopenko, Paul Johnson, Jaume Marrugat, Marju Orho-Melander, Aloysius G Lieverse, Ian Thomson, Vincent Mooser, Teresa Ferreira, Man Li, Benjamin J. Wright, Ryan P. Welch, Alessandra Allione, Stefan Blankenberg, Veryan Codd, Philippe Froguel, James C. Engert, Pekka Jousilahti, Klaus Stark, Toby Johnson, Cornelia M. van Duijn, Ivo Gut, John J.P. Kastelein, Thomas M. Morgan, Noël P. Burtt, Laura J. McCulloch, Tim D. Spector, Peter S. Chines, Timo T. Valle, Peter Shrader, Christian Dina, Diana Zelenika, Monika Stoll, Peter S. Braund, Harry Campbell, Rainer Rettig, Joep A.W. Teijink, Thomas Illig, Anne Tybjærg-Hansen, Peter Vollenweider, Guangju Zhai, Frits R. Rosendaal, Pau Navarro, James B. Meigs, Ghislain Rocheleau, Li Chen, Pilar Galan, Giuseppe Matullo, Henry Völzke, Samer S. Najjar, Christina Loley, N. Charlotte Onland-Moret, Alison H. Goodall, Riyaz S. Patel, S. Matthijs Boekholdt, Pim van der Harst, John R. B. Perry, Angela Doering, James S. Pankow, Gudmundur Thorgeirsson, Xin Yuan, Patricia B. Munroe, Abbas Dehghan, Tamara B. Smith, Valeriya Lyssenko, Mark I. McCarthy, Andrew T. Hattersley, Simon Futers, Barbara Thorand, Andre G. Uitterlinden, Simon J. Griffin, Winfried März, Nilesh J. Samani, Frank B. Hu, Valeria Romanazzi, Michael N. Weedon, Zouhair Aherrahrou, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Markus Perola, Stefania Bandinelli, Kathy Stirrups, Hilma Holm, Maja Barbalić, Kiran Musunuru, David Couper, David S. Siscovick, Guillaume Charpentier, Alexandre F.R. Stewart, Patrick Diemert, Leena Peltonen, Serge Hercberg, Robert Roberts, Michael Roden, Rhian Gwilliam, Guillaume Lettre, Eric J.G. Sijbrands, Lambertus A. Kiemeney, Martha Ganser, Silvia Polidoro, Kristin G. Ardlie, Stephen G. Ball, Kristina Bengtsson Boström, Katharine R. Owen, Paul E. de Jong, Felicity Payne, Wendy L. McArdle, Frances M K Williams, Paul Elliott, Roberto Elosua, Devin Absher, Kristian Midthjell, Jan D. Blankensteijn, Nelson B. Freimer, John C. Chambers, G. Kolovou, Karl Andersen, John Webster, Nicholas J. Wareham, Eric E. Schadt, Simon Heath, Diana Rubin, Solveig Gretarsdottir, Willem H. Ouwehand, Oluf Pedersen, Liming Qu, Sandra Eifert, Mary Susan Burnett, Paul Burton, Frank M. van Bockxmeer, Eleftheria Zeggini, Stephen M. Schwartz, Simon C. Potter, Tiinamaija Tuomi, Jeffrey R. Gulcher, David Altshuler, Harald Grallert, Hooman Allayee, Kari Stefansson, Anne H. Child, Sekar Kathiresan, Torben Hansen, Unnur Thorsteinsdottir, Isaac Subirana, Serena Sanna, Muredach P. Reilly, J. Wouter Jukema, H.-Erich Wichmann, François Cambien, Pier Angelica Merlini, Wiek H. van Gilst, Caroline S. Fox, Andrew Smith, Oliviero Olivieri, S Sohrabi, James F. Wilson, Gillian W. Cockerill, Guanming Wu, Andrew D. Morris, Carlos Iribarren, Joshua W. Knowles, Angelo Scuteri, Göran Berglund, Marilyn C. Cornelis, Pascal P. McKeown, Thorsten Reffelmann, Gérard Waeber, Les McNoe, Maris Laan, Dilip K. Naik, Karen L. Mohlke, Matthew Waltham, Rachel E. Clough, Claudia Langenberg, Seamus C. Harrison, Hany Hafez, Timon W. van Haeften, Carlotta Sacerdote, Robert Sladek, Nicola Martinelli, Declan Bradley, Cristen J. Willer, Sarah E. Hunt, Sven Cichon, Udo Seedorf, Winston Hide, Arne Schillert, Cuno S.P.M. Uiterwaal, Steve E. Humphries, Andre A van Rij, Stéphane Cauchi, Michael Boehnke, Beverley M. Shields, Suzannah Bumpstead, Diane M. Becker, Ron Do, Heribert Schunkert, Jacques S. Beckmann, Alistair S. Hall, Mike Sampson, Christine Proença, Lachlan J. M. Coin, Rob M. van Dam, Mohan U. Sivananthan, Martin Farrall, B. Gerry Hill, Simonetta Guarrera, Thijs T. W. van Herpt, Sonia S. Anand, Peter M. Nilsson, Arne Pfeufer, Rafn Benediktsson, Candace Guiducci, Lee M. Kaplan, Michel Marre, Thomas Meitinger, Annette F. Baas, Graham A. Hitman, Roberto Lorbeer, Flora Peyvandi, David J. Hunter, Seraya Maouche, G. Mark Lathrop, Michael R. Erdos, Thomas W. Mühleisen, L. Adrienne Cupples, Anne E. Hughes, Ayellet V. Segrè, Igor Rudan, Kijoung Song, Reijo Laaksonen, G. Bragi Walters, Christopher P. Nelson, Christopher S. Franklin, Richard M. Watanabe, Mattijs E. Numans, Christina Willenborg, Jeanette Erdmann, Alessandra Di Gregorio, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Anthony J. Balmforth, Yurii S. Aulchenko, Arne Schäfer, Catherine M. Rice, Tanja Zeller, Grace Yu, Augustine Kong, Matthew M Thompson, Diego Ardissino, Oliver Hofmann, John R. Thompson, J.B. Wild, Alexander Teumer, Ulf Gyllensten, David P. Strachan, Martin D. Tobin, Michael A. Kaiser, Steve McCarroll, Beverley Balkau, Stephen J. Newhouse, Michael Preuss, John A. Spertus, Janja Nahrstaedt, Neelam Hassanali, Gunnar Sigurdsson, Jaapjan D. Snoep, Angela Döring, Todd Green, D. Julian A. Scott, Christian Herder, Bo Isomaa, Anne U. Jackson, David Hadley, Domenico Girelli, Jes S. Lindholt, Toshiko Tanaka, Ruth Topless, Bernhard O. Boehm, Jana V. van Vliet-Ostaptchouk, Anna-Liisa Hartikainen, Anneli Pouta, Anuj Goel, Stefan Schreiber, Kristian Hveem, Gabriel Crawford, Pierre Meneton, Jürgen Schrezenmeir, Andre M. van Rij, Markku Laakso, Richa Saxena, Joshua C. Bis, Samy Hadjadj, Anders Franco-Cereceda, Noha Lim, Christopher J. Groves, Klaus Strassburger, Stefan E Matthiasson, M. Lourdes Sampietro, Josée Dupuis, Morris J. Bown, Cisca Wijmenga, Shu Ye, Jennifer Freyer, Anders Hamsten, Christian Hengstenberg, Olle Melander, Sarah Edkins, Alberto Smith, Luigi Ferrucci, Murielle Bochud, Lori L. Bonnycastle, Gregory T. Jones, Manuela Uda, Lasse Folkersen, Timothy M. Frayling, Giovanni Tognoni, Torben Jørgensen, Anna F. Dominiczak, Michiel L. Bots, Mario A. Morken, Ian Buysschaert, Colin N. A. Palmer, Andrew Hill, Mark J. Caulfield, Nicolas Sylvius, Nicole Soranzo, Susana Eyheramendy, Christopher Newton-Cheh, Eran Halperin, Mandy van Hoek, Stephen A. Badger, Paul Scheet, Gudmar Thorleifsson, Themistocles L. Assimes, Inês Barroso, Sheila Bingham, Nour Eddine El Mokhtari, Yvonne T. van der Schouw, Andrew J. Lotery, Heather M. Stringham, Marcus Dörr, Per Eriksson, Mark Walker, Mette Refstrup, Anna L. Gloyn, Ann-Christine Syvänen, John F. Peden, Diether Lambrechts, Arshed A. Quyyumi, Katherine S. Elliott, Jonathan Golledge, Edward G. Lakatta, Serkalem Demissie, Lewis C. Becker, Alex S. F. Doney, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Paul Norman, Marjo-Riitta Järvelin, Annette Peters, David Schlessinger, Janet T. Powell, Surgery, ICaR - Ischemia and repair, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Male, VASCULAR WALL, Genome-wide association study, 030204 cardiovascular system & hematology, Bioinformatics, Aortic aneurysm, 0302 clinical medicine, Risk Factors, Odds Ratio, Genetics(clinical), Genetics (clinical), Aorta, 0303 health sciences, Cardiovascular diseases [NCEBP 14], Homozygote, Abdominal aortic aneurysm, Organ Specificity, Data Interpretation, Statistical, CORONARY-ARTERY-DISEASE, Female, METALLOPROTEINASE, Sterol Regulatory Element Binding Protein 1, Low Density Lipoprotein Receptor-Related Protein-1, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Locus (genetics), Biology, Polymorphism, Single Nucleotide, DISSECTIONS, Article, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genome-wide associaton, Coronary-artery-disease, Susceptibility loci, Sequence variant, Vascular wall, Metalloproteinase, Atherosclerosis, Identification, Metaanalysis, Dissections, medicine.artery, Internal medicine, Cell Line, Tumor, medicine, Genetics, Humans, Genetic Predisposition to Disease, ddc:610, GENOME-WIDE ASSOCIATION, METAANALYSIS, 030304 developmental biology, Genetic association, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Aged, IDENTIFICATION, Case-control study, Odds ratio, medicine.disease, Endocrinology, ATHEROSCLEROSIS, SEQUENCE VARIANT, Genetic Loci, Case-Control Studies, Aortic Aneurysm, Abdominal, Follow-Up Studies, Genome-Wide Association Study
Abstract

Contains fulltext : 97601.pdf (Publisher’s version ) (Closed access) Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 x 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 x 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 x 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. 9 p.

Published
2011

116. Association between glycosylated haemoglobin A1c and endothelial function in an adult non-diabetic population

Author

Maria Arndt, Henri Wallaschofski, Matthias Nauck, Roberto Lorbeer, Henry Völzke, Marcus Dörr, Klaus Empen, Sabine Schipf, and Stephan B. Felix

Subjects
Adult, Male, medicine.medical_specialty, Vasodilator Agents, Population, Hyperemia, Type 2 diabetes, Risk Assessment, Nitroglycerin, Sex Factors, Risk Factors, Internal medicine, Diabetes mellitus, Germany, medicine, Glucose homeostasis, Humans, Endothelial dysfunction, education, Antihypertensive Agents, Subclinical infection, Aged, Glucose Metabolism Disorders, Aged, 80 and over, Glycated Hemoglobin, education.field_of_study, Chi-Square Distribution, business.industry, Middle Aged, 610 Medical sciences, Medicine, medicine.disease, Up-Regulation, Vasodilation, Endocrinology, Cross-Sectional Studies, ddc: 610, Cardiovascular Diseases, Study of Health in Pomerania, Case-Control Studies, Linear Models, Female, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business, Body mass index, Biomarkers
Abstract

Objective: Endothelial dysfunction precedes apparent atherosclerosis in humans and is asso-ciated with a number of cardiovascular risk factors, including Type 2 diabetes. To investigate the impact of long-term glucose homeostasis on endothelial function in an adult non-diabetic population, we analysed[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)

Published
2011

118. Greifswald Approach to Individualized Medicine (GANI_MED) – Rationale and Design

Author

Roberto Lorbeer, Marcus Dörr, Wolfgang Hoffmann, K Ott, M Nauck, U Völker, Henry Völzke, H Kock, H Assel, M Zygmunt, H. K. Kroemer, Stephan B. Felix, and M Hecker

Subjects
medicine.medical_specialty, business.industry, Public Health, Environmental and Occupational Health, Alternative medicine, Medicine, Medical physics, Personalized medicine, business
Published
2010

119. Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania

Author

Ralf Ewert, Stephan B. Felix, Nele Friedrich, Matthias Nauck, Marcus Dörr, Thorsten Reffelmann, Roberto Lorbeer, Daniel M. Robinson, Henri Wallaschofski, Alexander Krebs, Henry Völzke, and Klaus Empen

Subjects
Adult, Male, medicine.medical_specialty, Endothelium, Endocrinology, Diabetes and Metabolism, Population, Logistic regression, Endocrinology, Sex Factors, Internal medicine, Odds Ratio, Medicine, Humans, Insulin-Like Growth Factor I, education, Aged, 80 and over, education.field_of_study, business.industry, Confounding, General Medicine, Odds ratio, Middle Aged, Confidence interval, Insulin-Like Growth Factor Binding Proteins, Vasodilation, medicine.anatomical_structure, Cross-Sectional Studies, Insulin-Like Growth Factor Binding Protein 3, Logistic Models, Study of Health in Pomerania, Population study, Female, business
Abstract

ObjectiveIGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD).DesignCross-sectional population-based observational study.MethodsThe study population comprised 1482 subjects (736 women) aged 25–85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low.ResultsIn males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07–1.51;P=0.008) for decreased FMD for each decrement of IGF1s.d.after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74–1.05;P=0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12–1.75;P=0.003; females: OR 0.95, CI 0.77–1.16;P=0.595). There was no association between serum IGFBP3 levels and FMD in both sexes.ConclusionsLow serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.

Published
2010

122. Subject Index Vol. 4, Suppl. 1, 2015

Author

Daniel Tiller, Ulrich Schweizer, Claudia Stäubert, Stephan B. Felix, Maxi Cöster, Carolin Leonie Wienchol, Thomas Hermsdorf, Georg Brabant, Stefan Mergler, Kathrin Engels, Kathrin A. Schmohl, Gerd Krause, Roberto Lorbeer, Klaudia Brix, Josef Köhrle, Heike Heuer, Marcus Dörr, Kerstin Knoop, Ina Lehmphul, Nele Friedrich, Kerstin Krause, Daniel Rathmann, Druckerei Stückle, Maren Rehders, Maik Pietzner, Thomas F. Münte, Anita Kinne, Anna Göbel, Anne-Luise Dirk, Henry Völzke, Franziska Meyer, Anna-Luise Dirk, Noushafarin Khajavi, Eddy Rijntjes, Joanna Szumska, Anke Tönjes, Elke Hammer, Yaw Appiagyei-Dankah, Torsten Schöneberg, Beatrice Engelmann, Eva K. Wirth, Andrea M. Müller, Juliane Dinter, Kathrin Budde, Claudia Gebhardt, Gunnar Kleinau, Karin Halina Greiser, Karen Steinhoff, Nora Klöting, Onno E. Janssen, Karl Werdan, Ralf Schülein, David K. Grandy, Matthias Nauck, Julia Bischof, Helena Rakov, Dagmar Führer, Alexander Kluttig, Maria Qatato, S Hönes, Burkhard Goke, Denise Zwanziger, Melanie Wittner, Julika Lietzow, Lars C. Moeller, Thomas Thiele, Jessica Mühlhaus, Georg Homuth, Martin Göttlich, Christine Spitzweg, Swen Hesse, Birgit Köhler, Till Ittermann, Peter Bartenstein, Katrin M. Hinz, Peter J. Nelson, John T. Heiker, Marcus Heldmann, Uwe Völker, Nathalie Schwenk, Heike Biebermann, and Juliane Weiner

Subjects
Gerontology, Index (economics), business.industry, Endocrinology, Diabetes and Metabolism, Medicine, Subject (documents), business
Published
2015

123. Angiopoietin-2, its soluble receptor Tie-2 and subclinical cardiovascular disease in a population-based sample

Author

Marcello Ricardo Paulista Markus, Anne Grotevendt, Matthias Nauck, Henri Wallaschofski, Bettina von Sarnowski, Stephan B. Felix, Sebastian E. Baumeister, Wolfgang Lieb, Roberto Lorbeer, Marcus Dörr, Ramachandran S. Vasan, and Henry Völzke

Subjects
Adult, Male, medicine.medical_specialty, Cross-sectional study, Population, Disease, Rate ratio, Carotid Intima-Media Thickness, Angiopoietin-2, Risk Factors, Germany, medicine.artery, Internal medicine, Humans, Medicine, Common carotid artery, education, Receptor, Survival rate, Aged, Retrospective Studies, Subclinical infection, Aged, 80 and over, education.field_of_study, business.industry, Incidence, Angiopoietin 2, Population based sample, Middle Aged, Receptor, TIE-2, Survival Rate, Cross-Sectional Studies, Endocrinology, Intima-media thickness, Cardiovascular Diseases, Echocardiography, Population Surveillance, Study of Health in Pomerania, Immunology, Disease Progression, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract

Objective Higher circulating Angiopoietin-2 (Ang-2) levels predict cardiovascular events and mortality in clinical samples and in the general population. To better understand the underlying mechanisms, we investigated the association of circulating Ang-2 and sTie-2 (the soluble form of the Ang-2 receptor) levels with various measures of subclinical cardiovascular disease. Methods Cross-sectional data of 3204 participants (1654 women) aged 25–88 years from the population-based Study of Health in Pomerania were analysed. LV mass (LVM) and fractional shortening were determined echocardiographically as indices of cardiac structure and function, respectively. Intima media thickness (IMT) of the common carotid artery, the number of carotid plaques and flow-mediated dilation (FMD) were used to characterise large and medium-sized arterial structure and function. Results Multivariable-adjusted linear and negative binomial regression models revealed an inverse association of circulating Ang-2 levels (independent variable) with fractional shortening (s=−0.51 per 1 SD increment; 95% CI −0.86 to −0.16, p=0.005) and a positive association with number of carotid plaques (rate ratio=1.04 95% CI 1.01 to 1.07, p=0.019). No associations of Ang-2 or sTie-2 with LVM, IMT and FMD were found. Conclusions Circulating Ang-2 levels were associated with select subclinical cardiovascular disease traits, consistent with the notion that the Ang-2-pathway plays a role in mediating cardiovascular morbidity.

Published
2015

125. Genetic diversity is a predictor of mortality in humans

Author

Albert V. Smith, Douglas P. Kiel, Jessica D. Faul, Stefania Bandinelli, Nese Direk, Thomas Lumley, Denis A. Evans, Luigi Ferrucci, Joanne M. Murabito, Wei Zhao, David R. Weir, Vilmundur Gudnason, Jennifer A. Smith, Georg Homuth, Alexander Teumer, Jennifer A. Brody, James S. Pankow, Toshiko Tanaka, Saira Saeed Mirza, Dan E. Arking, John M. Starr, Bruce M. Psaty, Nathan A. Bihlmeyer, Kathryn L. Lunetta, André G. Uitterlinden, Gail Davies, Lei Yu, Sharon L.R. Kardia, Roberto Lorbeer, Lenore J. Launer, Andrew B. Singleton, Hans J. Grabe, Henning Tiemeier, Josef Coresh, Yongmei Liu, Philip L. De Jager, Ian J. Deary, Thomas Kocher, David C. Liewald, Mike A. Nalls, M. A. Ikram, David A. Bennett, Gudny Eiriksdottir, Junko Oshima, Nora Franceschini, Tamara B. Harris, Paul Redmond, David Karasik, Melissa E. Garcia, Hanyue Li, Michael Allerhand, Anish Scaria, Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, and Psychiatry

Subjects
0106 biological sciences, Heterozygote, Survival, Population, Population genetics, Genome-wide association study, Disease, Biology, Polymorphism, Single Nucleotide, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetics, GWAS, Humans, Genetics(clinical), ddc:610, Mortality, Allele, education, Genetics (clinical), Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, education.field_of_study, Genetic diversity, Heterozygosity, Proportional hazards model, 3. Good health, Sample size determination, Research Article, Human, Genome-Wide Association Study
Abstract

Background It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. Results We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person’s risk of death by 1.57%. Conclusions This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival. Electronic supplementary material The online version of this article (doi:10.1186/s12863-014-0159-7) contains supplementary material, which is available to authorized users.

126. Do patients with type 1 and type 2 diabetes really have an impaired endothelial function? A population-based propensity score matching analysis

Author

Henri Wallaschofski, Stephan B. Felix, Sabine Schipf, Wolfgang Kerner, Roberto Lorbeer, Klaus Empen, Marcus Dörr, Henry Völzke, Matthias Nauck, and Thorsten Reffelmann

Subjects
Adult, Male, medicine.medical_specialty, Brachial Artery, Epidemiology, Endocrinology, Diabetes and Metabolism, Hyperemia, Type 2 diabetes, Diabetic angiopathy, FMD, Young Adult, Risk Factors, Diabetes mellitus, medicine.artery, Internal medicine, Germany, medicine, Humans, Brachial artery, Propensity Score, Aged, Original Investigation, Aged, 80 and over, Type 1 diabetes, business.industry, Confounding, Case-control study, Endothelial function, Middle Aged, medicine.disease, Vasodilation, Flow-mediated dilation, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Regional Blood Flow, Case-Control Studies, Propensity score matching, Female, Endothelium, Vascular, business, Cardiology and Cardiovascular Medicine, Diabetic Angiopathies
Abstract

Background Previous studies suggested an impaired endothelial function in patients with diabetes. However, the validity of this finding may be limited by the lack of adequate adjustment for further cardiovascular confounders. We assessed endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in patients with either type 1 or type 2 diabetes in comparison with non-diabetic controls. Methods The study population comprised 1487 subjects including 122 subjects with type 2 diabetes, aged 25 to 85, from the population-based Study of Health in Pomerania, and 65 outpatients, aged 23 to 75, with type 1 diabetes. FMD measurements were performed using standardized ultrasound techniques. Subjects with type 1 and type 2 diabetes were matched 1:4 to healthy controls using propensity score matching. Results Neither type 1 diabetes (β = 0.142; SE = 0.568, p = 0.803) nor type 2 diabetes (β = 0.107; SE = 0.340, p = 0.752) were significantly associated with FMD in comparison with their non-diabetic controls after adjustment for major cardiovascular confounders like age, gender, body mass index, smoking status, hypertension, antihypertensive medication, LDL and HDL cholesterol levels. Conclusions In this population-based study comparing adjusted FMD values of diabetic individuals with adequately matched controls, propensity score analyses revealed no association between diabetes and endothelial function. Since these findings are in discordance with the majority of previous reports, we suggest performing similar analyses using data from other population-based studies.

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