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Objetivos: Los grupos de nivel social más bajo tienen habitualmente una dieta menos saludable. El objetivo de este estudio es comparar la adhesión al patrón de dieta mediterránea entre diferentes grupos demográficos y sociales de la población adulta. Métodos: Se realizó un estudio transversal en regiones del sur y norte de España, en voluntarios sanos (15.634 varones y 25.812 mujeres) de 29 a 69 años de edad, miembros de la cohorte EPIC en España. Se tuvo en cuenta el consumo de nueve grupos de alimentos para definir el patrón de dieta mediterránea: vegetales, frutas, legumbres, cereales, carne roja, pescado, aceite de oliva, leche y productos lácteos y vino. Se aplicaron dos técnicas de análisis: comparación de la media diaria de consumo de cada grupo, y el cálculo de un escore global para todos los alimentos, por nivel educacional y clase social de origen. Resultados: Los grupos de nivel educacional más bajo consumen mas cereales y legumbres, pero menos vegetales, aceite de oliva (las mujeres), leche y productos lácteos (los varones). El consumo de vino está positivamente asociado con la educación en las mujeres y negativamente asociado en los varones. Calculando una puntuación para medir la adhesión global al patrón de dieta mediterránea, las diferencias por cada grupo de alimentos se compensan, y no hay variaciones según el nivel educacional, aunque existen pequeñas diferencias en la clase social de origen (22,52 en la clase más baja y 21,98 en la clase más alta). El índice de adhesión es más bajo en los adultos jóvenes y mujeres, y ligeramente más alto en las poblaciones del sur (23,53 en Murcia) que en las del norte de España (21,64 en Asturias). Conclusiones: Los resultados sugieren que el patrón de dieta mediterránea es bastante uniforme, al menos en las poblaciones adultas de las áreas incluidas en el estudio.Objectives: Lower social classes tend to eat a less healthy diet. The aim of this study was to compare adherence to the Mediterranean dietary pattern among different demographic and social groups in the adult population. Methods: A cross-sectional study was performed in southern and northern regions of Spain in healthy volunteers (15,634 men and 25,812 women), aged 29-69 years, who were members of the European Prospective Investigation on Cancer cohort in Spain. Nine groups of food were included in the definition of the Mediterranean diet: vegetables and garden products, fruits, pulses, cereals, red meat, fish, olive oil, milk and milk products, and wine. Two techniques were used in the analysis: comparison of the mean daily intake of each group and calculation of an overall score for all the foods according to educational level ang original social class. Results: Groups with the lowest educational levels consumed more cereals and pulses and lower quantities of vegetables, olive oil (women), milk and milk products (men). Wine consumption was positively associated with education in women and was negatively associated in men. Calculation of a score to measure overall adherence to the Mediterranean dietary pattern eliminated differences according to each food category. No variations were found according to educational level, but small differences were found in original social class. The adherence score was lowest in young adults and women and was slightly higher in the south than in the north of Spain. Conclusions: The results suggest that the Mediterranean dietary pattern is fairly uniform, at least in the adult population of the regions included in this study.

Background and Aim: Body shape and anthropometrics are well-known risk factors for cardiovascular diseases (CVD) and mortality. Hand-grip strength (HGS) is also a meaningful marker of health and a promising predictor of CVD and mortality. There is a lack of studies that have systematically investigated associations between body shape and anthropometrics with HGS. In a population-based study, we investigated if anthropometric markers derived from 3D body scanning are related to HGS., Methods and Results: We used the data of 1,599 individuals aged 36 to 93 years, who participated in the Study of Health in Pomerania. A total of 87 anthropometric markers, determined by a 3D body scanner, were included in the analysis. Anthropometric measurements were standardized and used as exposure variables. HGS was measured with a hand dynamometer and used as outcome. Sex-stratified linear regression models adjusted for age and height were used to relate standardized anthropometrics and HGS. Anthropometric markers were ranked according to -log-p-values. In men, left and right forearm circumference, left arm length to neck (C7), left forearm length, and forearm-fingertip length were most strongly related to HGS. In women, right forearm circumference, forearm-fingertip length, shoulder breadth, left forearm circumference, and right wrist circumference showed the most significant associations with HGS. The final prediction models contained 13 anthropometric markers in males (R 2 =0.54) and eight anthropometric markers in females (R 2 =0.37)., Conclusions: The identified parameters may help estimate HGS in the clinical setting. However, studies in clinical settings are essential to validating our findings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aim: Growing body of evidence consistently link obesity and inflammation, Although the direction of the association is still unclear. We aimed to investigate longitudinal associations of body anthropometric, composition and fat distribution parameters with inflammatory markers and vice versa., Method and Results: We used data from 2464 individuals of the SHIP-TREND cohort with a median follow-up of 7 years. Linear regression models adjusted for confounders were used to analyze associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) at baseline with changes in inflammatory markers (C-reactive protein (CRP), white blood cell (WBC), fibrinogen) and vice versa. Higher level of anthropometric markers at baseline were associated with an increase in the change of inflammatory markers. A 13.5 cm higher waist circumference (WC), 16.0 kg body weight and 7.76 % relative fat mass (FM) at baseline was associated with a change in CRP of 0.52 mg/L (95 % confidence interval [CI]: 0.29 to 0.74), 0.51 mg/L (95 % CI: 0.29; 0.74) and 0.58 mg/L (95 % CI: 0.34; 0.82) respectively. Absolute FM showed the strongest association with changes in serum fibrinogen levels (β for 8.69 kg higher FM: 0.07 g/L; 95 % CI: 0.05; 0.09). Baseline inflammatory markers were only associated with changes in hip circumference., Conclusion: Our study indicates the importance of anthropometric, body composition and fat distribution markers as a risk factor for the development of inflammation. To prevent inflammatory-related complications, important is to take measures against the development of obesity., Competing Interests: Declaration of competing interest The authors do not have any disclosures to report., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aim: The associations of body composition markers derived from different modalities with inflammatory markers are unclear. The aim of this study was to determine associations of the body composition markers from different modalities with inflammatory markers in a population-based study., Methods and Results: We analyzed data from 4048 participants (2081 women, 51.4%) aged 20-84 years. Linear regression models adjusted for confounding were used to analyze the association of classic anthropometry markers, absolute and relative fat mass, absolute fat-free mass (FFM), and body cell mass (BCM) assessed by bioelectrical impedance analysis, subcutaneous, visceral, and liver fat from magnetic resonance imaging (MRI), with markers of inflammation. We found positive associations of classic anthropometry markers, total body fat, subcutaneous, visceral, and liver fat, with all inflammatory markers. Waist circumference (WC) showed the strongest association with high-sensitivity C-reactive protein (hsCRP) (β: 1.39; 95% confidence interval [CI]: 1.22 to 1.56) and white blood cell (WBC) (0.39; 0.29 to 0.48), whereas visceral fat showed the strongest association with ferritin (41.9; 34.7 to 49.0). Relative body fat was strongly associated with hsCRP (1.39; 1.20 to 1.58), fibrinogen (0.29; 0.27 to 0.32), and WBC (0.35; 0.25 to 0.46). Conversely, we found inverse associations of body height, FFM, and BCM with hsCRP, fibrinogen, and WBC., Conclusions: Our study indicates the importance of WC as an easily measured marker for early inflammation. MRI-assessed markers of central obesity seem to be most strongly related to ferritin., Competing Interests: Declaration of competing interest The authors do not have any disclosures to report., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The definition of the metabolic syndrome consists of five components. The underlying measurements are subject to intra-individual variability. This repeated measurements study investigated the impact of intra-individual measurement variability on the stability of the diagnosis of metabolic syndrome over 12 months., Methods and Results: Twenty-five employees of the University Medicine Greifswald aged 22-70 years were examined once a month over one year. Examinations included blood sampling and anthropometric and blood pressure measurements. Laboratory measurements included glucose, cholesterol (high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), and triglycerides. The metabolic syndrome was defined according to the International Diabetes Federation modified for non-fasting blood samples. Variations in continuous metabolic markers were assessed using coefficients of variation (CV) and intra-class correlation coefficients (ICC). Overall eight participants (32%) were categorized at least once within 12 months as having a metabolic syndrome; in none of those metabolic syndrome was found consistently over the study follow-ups. The Cohen's Kappa for metabolic syndrome was 0.57. CV was highest for triglycerides (27.5%) followed by glucose (10.1%), LDL- (9.5%), and HDL-cholesterol (8.6%). ICC's were lowest for glucose (0.51), triglycerides (0.65), systolic (0.68), and diastolic blood pressure (0.69)., Conclusion: We showed that the measurement of biomarkers defining the metabolic syndrome is a time-varying condition with implications for the concept of the metabolic syndrome. To account for this uncertainty in prevalence studies we propose to identify uncertain cases according to the current definition of the metabolic syndrome. For analysing associations we recommend to apply probabilistic sensitivity analyses., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aim: While there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states in the population-based Study., Methods and Results: We included data from 1622 individuals with MRI data, who did not have known type 2 diabetes (T2DM). Using an oral glucose tolerance testing, participants were classified as having isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) or previously unknown T2DM. Hepatic iron and fat contents were assessed through quantitative MRI. We undertook linear and multinomial logistic regression models adjusted for potential confounders and MRI-assessed hepatic fat content to examine the association of hepatic iron overload with different glucose intolerance states or continuous markers of glucose metabolism. MRI-assessed hepatic iron overload was positively associated only with both 2-h plasma glucose (β = 0.32; 95%CI 0.04-0.60) and the combined IFG + IGT category (relative risk ratio = 1.87; 95%CI 1.15-3.06). No significant associations were found between hepatic iron overload and other glucose intolerance states or biomarkers of glucose metabolism, independently of potential confounders., Conclusions: MRI-assessed hepatic iron overload was associated with higher 2-h glucose concentrations and the combined IFG + IGT category, but not with other glucose intolerance states. Our findings suggest a weak adverse impact of hepatic iron overload on glucose metabolism, but further studies are needed to confirm these findings., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Sphingosine-1-phosphate (S1P) is a sphingolipid which influences the immune and vascular system. The relationship between S1P and vascular disease in the general population is currently unclear. We explored the relation between S1P and vascular markers, (i.e. ankle-brachial index (ABI), carotid intima-media thickness (cIMT), presence of carotid atherosclerotic plaques and brachial artery flow-mediated dilation (FMD)., Methods: S1P was measured by liquid chromatography-tandem mass spectrometry in the population-based Study of Health in Pomerania (SHIP-TREND-0). Subjects with prevalent cancer, severe renal insufficiency, history of myocardial infarction and extreme values for S1P were excluded. Sex stratified linear regression models adjusted for age, smoking and waist-to-hip ratio were used., Results: A total of n = 3643 participants (52% women, median age 51, 25th and 75th percentiles 39 and 63 years) were included. In men, a 1 standard deviation higher S1P concentration was associated with a significantly greater cIMT (β: 0.0057 95%-confidence interval [CI]: 0.00027-0.0112 mm; p = 0.04) and a lower ABI (β: -0.0090 95% CI: -0.0153 to -0.0029; p < 0.01). In women, S1P was also positively associated with cIMT (β: 0.0044 95% CI: 0.0001-0.0086 mm; p = 0.04)., Conclusions: We found that S1P was positively related to a greater cIMT in both sexes and a lower ABI in men. There was no association of S1P with any of the other investigated markers. Future studies are warranted to assess the suitability of S1P as a biomarker for vascular disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Assessment of comprehensive lipoprotein subclass profiles in adolescents and their relation to vascular disease may enhance our understanding of the development of dyslipidemia in early life and inform early vascular prevention., Methods: Nuclear magnetic resonance was used to measure lipoprotein profiles, including lipids (cholesterol, free cholesterol, triglycerides, phospholipids) and apolipoproteins (apoB-100, apoA1, apoA2) of 17 lipoprotein subclasses (from least dense to densest: VLDL-1 to -6, IDL, LDL-1 to -6, HDL-1 to -4) in n = 1776 14- to 19-year olds (56.6% female) and n = 3027 25- to 85-year olds (51.5% female), all community-dwelling. Lipoprotein profiles were related to carotid intima-media thickness (cIMT) as ascertained by sonography., Results: Adolescents compared to adults had lower triglycerides, total, LDL, and non-HDL cholesterol, and apoB, and higher HDL cholesterol. They showed 26.6-59.8% lower triglyceride content of all lipoprotein subclasses and 21.9-51.4% lower VLDL lipid content. Concentrations of dense LDL-4 to LDL-6 were 36.7-40.2% lower, with also markedly lower levels of LDL-1 to LDL-3, but 24.2% higher HDL-1 ApoA1. In adolescents, only LDL-3 to LDL-5 subclasses were associated with cIMT (range of differences in cIMT for a 1-SD higher concentration, 4.8-5.9 μm). The same associations emerged in adults, with on average 97 ± 42% (mean ± SD) larger effect sizes, in addition to LDL-1 and LDL-6 (range, 6.9-11.3 μm) and HDL-2 to HDL-4, ApoA1, and ApoA2 (range, -7.0 to -17.7 μm)., Conclusions: Adolescents showed a markedly different and more favorable lipoprotein profile compared to adults. Dense LDL subclasses were the only subclasses associated with cIMT in adolescents, implicating them as the potential preferred therapeutic target for primary prevention of cardiovascular disease at this age. In adults, associations with cIMT were approximately twice as large as in adolescents, and HDL-related measures were additionally associated with cIMT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Fat mass and fat-free mass may play independent roles in mortality risk but available studies on body composition have yielded inconsistent results., Objective: The aim was to determine the relations of body fat mass and fat-free mass to risk of mortality., Methods: In pooled data from 7 prospective cohorts encompassing 16,155 individuals aged 20 to 93 y (median, 44 y), we used Cox regression and restricted cubic splines to estimate HRs and 95% CIs for the relation of body composition, measured by bioelectrical impedance analysis, to total mortality. We adjusted for age, study, sex, ethnicity, history of diabetes mellitus, education, smoking, physical activity, and alcohol consumption., Results: During a median follow-up period of 14 y (range, 3-21 y), 1347 deaths were identified. After mutual adjustment for fat mass and fat-free mass, fat mass showed a J-shaped association with mortality (overall P value < 0.001; P for nonlinearity = 0.003). Using a fat mass index of 7.3 kg/m2 as the reference, a high fat mass index of 13.0 kg/m2 was associated with an HR of 1.56 (95% CI: 1.30, 1.87). In contrast, fat-free mass showed an inverse association with mortality (overall P value < 0.001; P for nonlinearity = 0.001). Compared with a low fat-free mass index of 16.1 kg/m2, a high fat-free mass of 21.9 kg/m2 was associated with an HR of 0.70 (95% CI: 0.56, 0.87)., Conclusions: Fat mass and fat-free mass show opposing associations with mortality. Excess fat mass is related to increased mortality risk, whereas fat-free mass protects against risk of mortality. These findings suggest that body composition provides important prognostic information on an individual's mortality risk not provided by traditional proxies of adiposity such as BMI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and impaired myocardial function. Endomyocardial biopsies (EMB) enable immunohistochemical and molecular characterization of this disease. However, knowledge about specific molecular patterns and their relation to cardiac function in both ventricles is rare. Therefore, we performed a mass spectrometric analysis of 28 paired EMBs of left (LV) and right ventricles (RV) of patients with DCM or suspected myocarditis allowing quantitative profiling of 743 proteins. We analysed associations between protein abundance of LV and RV as well as the echocardiographic parameters LVEF, TAPSE, LVEDDI, and RVEDDI by linear regression models. Overall, more LV than RV proteins were associated with LV parameters or with RVEDDI. Most LV and RV proteins increasing in level with impairing of LVEF were annotated to structural components of cardiac tissue. Additionally, a high proportion of LV proteins with metabolic functions decreased in level with decreasing LVEF. Results were validated with LV heart sections of a genetic murine heart failure model. The study shows, that remodelling and systolic dysfunction in DCM is mirrored by distinct alterations in protein composition of both ventricles. Loss of LV systolic function is reflected predominantly by alterations in proteins assigned to metabolic functions in the LV whereas structural remodelling was more obvious in the RV. Alterations related to intermediate filaments were seen in both ventricles and highlight such proteins as early indicators of LV loss of function. SIGNIFICANCE: The present study report protein sets in the RV and the LV being associated with ventricular function and remodelling in DCM. Protein abundances in the LV and the RV emphasize and expand current knowledge on pathophysiological changes in heart failure and DCM. While RV and LV EMBs do not differ concerning diagnostic assessment of inflammatory status and virus persistence, additional information reflecting disease severity associated protein alterations can be gained by EMB protein profiling. RV and LV protein data provided complementary information. The protein pattern of the LV reflects metabolic changes and an impaired energy production, which is associated with the degree of LV systolic dysfunction and remodelling and may yield important information about the disease status in DCM. On the other hand, at this disease stage of DCM with still preserved RV function, RV alterations in structural proteins may reflect myocardial compensatory protective mechanisms for maintenance of structure and cellular function. The study highlight particular proteins being of interest as heart failure biomarkers in both ventricles which seem to reflect the severity of the disease. Further comparative studies between different HF aetiologies have to evaluate those proteins as markers specific for DCM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction. The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital. SIGNIFICANCE: Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cardiodepressant antibodies contribute to cardiac dysfunction in dilated cardiomyopathy (DCM). Changes in immunoglobulin G (IgG) glycosylation modulate the activity of various autoimmune diseases and influence disease activity as well as severity of various autoimmune diseases. We hypothesized that alterations in IgG glycosylation are involved in the disease course of DCM., Methods and Results: IgG glycosylation was analyzed in plasma samples of 50 DCM patients using a lectin-based ELISA. Negative inotropic (cardiodepressant) activity (NIA) of antibodies was assessed by measuring the effect of purified DCM-IgG on the shortening of isolated rat cardiomyocytes by means of a video-edge detection system. IgG obtained from plasma of healthy blood donors served as control. DCM-IgG contained significantly less sialic acid (-25%) and galactose (-16%; both P < 0.001), but showed no significant differences in core-fucosylation compared to controls. Interestingly, IgG with NIA displayed a lower percentage of sialylation (-16%, P < 0.001) core-fucosylation (-15%, P = 0.015) and galactosylation (-10%, P = 0.129) than IgG without NIA. The extent of NIA was directly associated with IgG sialylation (r = 0.68; P < 0.001) and galactosylation (r = 0.37; P = 0.001)., Conclusion: Reduced sialylation and galactosylation of IgGs enhances their cardiodepressant activity in DCM indicating that changes in IgG glycosylation may be involved in the pathogenesis of DCM., (Copyright © 2019. Published by Elsevier B.V.)

Background: Insulin-like growth factor 1 (IGF-1) and its main binding protein insulin-like growth factor binding protein 3 (IGFBP-3) have been related to several cardiovascular diseases. The relation with atrial fibrillation (AF) is largely unknown., Objective: The objective of this study was to investigate the association of IGF-1 and IGFBP-3 levels with prevalent and incident AF in a large population-based study., Methods: Data from the Study of Health in Pomerania (SHIP) were collected. At presentation, a medical examination, standardized electrocardiographic assessment, and measurements of serum IGF-1 and IGFBP-3 levels were performed. Incident AF was assessed in individuals without AF at baseline (SHIP-1) who developed AF during follow-up (SHIP-2; after a mean of 5.2 years)., Results: Of 3160 participants, 66 (2.1%) exhibited AF at baseline. IGF-1 levels and IGF-1/IGFBP-3 ratios were significantly lower in individuals with AF than in those without AF (IGF-1: 104.2 ± 41.6 ng/mL vs 142.9 ± 53.5 ng/mL, P < .001 and IGF-1/IGFBP-3: 0.031 ± (0.009 ng/mL vs 0.036 ± 0.010 ng/mL, P = .006, respectively). Multivariable-adjusted logistic regression models showed that a low IGF-1/IGFBP-3 ratio was associated with prevalent AF (odds ratios 0.67; 95% confidence interval 0.48-0.94; P = .021). Of 1817 individuals without AF at baseline, 27 (1.5%) developed AF during follow-up. In these participants, IGF-1 levels, but not IGF-1/IGFBP-3 ratios, were significantly lower (IGF-1: 113.3 ± 38.6 ng/mL vs 147.2 ± 51.6 ng/mL, P = .013 and IGF-1/IGFBP-3: 0.033 ± 0.008 ng/mL vs 0.036 ± 0.010 ng/mL, P = .176)., Conclusion: Low IGF-1/IGFBP-3 ratios are associated with a higher prevalence of AF. There seems to be a similar impact in incident AF., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: We estimated the association of changes in body weight, waist circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood pressure and incident hypertension using data from four German population-based studies., Methods: We analyzed data from 4467 participants, aged 21 to 82 years not taking antihypertensive medication and not having type 2 diabetes mellitus or a history of myocardial infarction at baseline and follow-up, from four population-based studies conducted in Germany. Body weight, WC, and blood pressure were measured at baseline and follow-up (median follow-up of the single studies 4 to 7 years). FM and FFM were calculated based on height-weight models derived from bioelectrical impedance studies. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Confounder-adjusted linear and logistic regressions were used to associate changes in anthropometric markers with changes in blood pressure, incident hypertension, and incident normalization of blood pressure., Results: In a pooled dataset including all four studies, increments in body weight, WC, FM, and FFM were statistically significantly associated with incident hypertension and changes in systolic and diastolic blood pressure over time. Decreases in body weight, FM, and FFM were significantly associated with incident normalization of blood pressure., Conclusions: Our data suggests that the well-established association between obesity and blood pressure levels might be more related to body composition rather than to total body weight per se. Our findings indicate that gaining or losing FFM has substantial impact on the development or reversion of hypertension., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Myeloid differentiation factor-2 (MD-2) has been shown to be an important modulator of the innate immune system, but its role in cardiac diseases is unknown. We investigated whether MD-2 plays a role as risk predictor and contributor in dilated cardiomyopathy (DCM)., Methods and Results: We included 174 patients with reduced left ventricular (LV) ejection fraction (LVEF <45%) due to DCM. Coronary artery disease and severe valvular diseases were excluded in all patients by angiography or echocardiography. Cardiac inflammation, viral infection and MD-2 expression were analyzed from right ventricular endomyocardial biopsies. MD-2 was quantified by ELISA in serum upon first hospital admission. Myocyte contractility and inflammatory response after stimulation with recombinant MD-2 protein were analyzed in isolated rat cardiomyocytes. Median follow-up of the patients was 3.51 years (2.73; 4.48) with 34 deaths. Absolute mortality risk increases in patients displaying a MD-2 serum concentration greater than the median (302 ng/ml) was 23% (P < 0.0001). Age- and sex-adjusted Cox regression analyses demonstrated that mortality risk was highly related to MD-2 concentrations (P < 0.001), but not to age or sex. An increase of 100 ng/ml in the MD-2 level was associated with an absolute mortality risk increase of 50.4%. Receiver operating characteristic (ROC) analyses showed no difference between MD-2 and nterminal-pro brain natriuretic peptide (NT-pro-BNP), while the combination of both MD-2 and NT-pro-BNP resulted in a significantly increased capability of risk prediction when compared to NT-pro-BNP alone (P = 0.014). In-vitro, recombinant MD-2 decreases cell shortening and modulates cytokine activation in isolated cardiomyocytes., Conclusion: MD-2 predicts long-term outcome in DCM patients and improves mortality risk prediction capability compared to NT-pro-BNP alone. In addition, MD-2 exerts direct negative inotropic effects on isolated cardiomyocytes in-vitro. Further randomized trials should confirm MD-2 as a diagnostic and therapeutic target., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: A potential causal relationship between thyroid function and type 2 diabetes mellitus is currently under debate, but the current state of research is limited. Our aim was to investigate the association of thyroid hormone levels with prevalent and incident type 2 diabetes mellitus (T2DM) in two representative studies., Methods and Results: Analyses are based on data from the Study of Health in Pomerania (SHIP), a German population based cohort with 4308 individuals at baseline and 3300 individuals at a five-year follow-up, and from INTER99, a Danish population-based randomized controlled trial with 6784 individuals at baseline and 4516 individuals at the five-year-follow-up. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentrations were measured in both studies, while free triiodothyronine was measured in SHIP only. T2DM was defined by self report or intake of anti-diabetic medication. Neither in SHIP nor in INTER99 we detected significant associations of serum TSH levels with prevalent or incident T2DM. Serum fT4 levels were significantly positively associated with prevalent T2DM in SHIP and INTER99. In longitudinal analyses baseline levels of fT4 were significantly positively associated with incident T2DM in SHIP (RR per pmol/L = 1.07; 95%-CI = 1.05-1.10), while this association barely missed statistical significance in INTER99 (RR per pmol/L = 1.03; 95%-CI = 0.99-1.06). In SHIP baseline fT3 levels were significantly associated with incident T2DM (RR per pmol/L = 1.21; 95%-CI = 1.16-1.27)., Conclusion: We demonstrated positive associations of thyroid hormones with prevalent and incident type 2 diabetes mellitus suggesting that hyperthyroxinemia may contribute to the pathogenesis of this condition., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The bioactive signaling lipid sphingosine-1-phosphate (S1P) is a potential biomarker for cardiovascular disease (CVD). To date, no reference intervals for S1P have been defined. This study aims to establish a reference range for serum S1P in healthy individuals., Methods: We determined reference intervals for S1P levels according to gender and age in a sample of 1339 healthy participants of the Study of Health in Pomerania (SHIP)-TREND cohort after exclusion of subjects with CVD, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes, chronic kidney disease stadium III or IV, or body mass index (BMI)>30kg/m 2 . Serum S1P was measured by liquid chromatography-tandem mass spectrometry., Results: The median age of the participants was 41 (25th; 75th percentile 32; 51) years, 65% were women. The median serum concentration of S1P was 0.804 (0.694; 0.920) μmol/L. No association with gender and age was observed. The overall reference interval was 0.534-1.242μmol/L (2.5th; 97.5th percentile). Further exclusion of smokers, individuals with BMI>25kg/m 2 or elevated lipid levels did not significantly affect median S1P concentrations., Conclusions: This study provides reference intervals for serum S1P in healthy individuals. Total serum S1P concentrations vary irrespectively of age, gender, BMI or smoking status., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential biomarker is available to predict improvement of cardiac function after therapy accurately. This shotgun proteome study aims to disclose the differences in the endomyocardial proteome between patients with improved LVEF after IA/IgG (responders) and those without improvement (non-responders) before therapy start. Comparative analysis revealed 54 differentially abundant proteins that were mostly confined to carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these proteins revealed highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA/IgG therapy., Significance: We evaluated the differences in the myocardial proteome of responder and non-responder DCM patients before immunoadsorption therapy and identified a number of differentially abundant proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results. Proteins S100-A8, perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption therapy treatment., (Copyright © 2016. Published by Elsevier B.V.)

Objectives: Most of the observed associations of androgens and sex hormone-binding globulin (SHBG) with subclinical cardiovascular disease (CVD) stem from selected study samples with immunoassay-based hormone measurements. Thus, we used a large population-based sample with total testosterone (TT) and androstenedione (ASD) concentrations measured by liquid chromatography-tandem mass spectrometry., Design: Data of 2140 individuals (mean age: 60,8 years) from the cohort Study of Health in Pomerania were assessed at baseline and 5-year follow-up., Methods: Multivariable regression models were implemented to assess cross-sectional and longitudinal associations of TT, free testosterone (fT), ASD, SHBG and dehydroepiandrosterone-sulphate (DHEAS) with measures of subclinical CVD including intima media thickness (IMT), carotid plaques, left ventricular mass (LVM), fractional shortening (FS), relative wall thickness (RWT), and left ventricular geometry., Results: Cross-sectional analyses yielded an association of TT with IMT in women (β-coefficient per log unit increase: 0.02; 95% CI: 0.007; 0.45) and ASD with FS in both sexes (men: β-coefficient: -2.94; 95% CI: -4.75; -1.12; women: β-coefficient: 1.64; 95% CI: 0.55; 2.73). In longitudinal analyses, DHEAS was positively associated with FS change (β-coefficient: 2.34; 95% CI: -0.59; 4.08). In women, SHBG was positively associated with incident plaques (Q1 vs. Q3 (Ref.): β-coefficient: 1.35; 95% CI: 1.04; 1.74). In both sexes, longitudinal analyses showed no consistent association of TT with subclinical CVD., Conclusions: Despite several sex-specific associations of androgens and SHBG with subclinical CVD, the present representative study for the age group ≥45 years among men and women from the general population detected no consistent associations in longitudinal analyses., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample., Methods: We analyzed data from 3090 women and men, aged 20-81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software., Results: The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF., Conclusions: Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Here, we report a widely and generally applicable strategy to obtain reliable information in high-throughput protein screenings of enzyme mutant libraries. The method is based on the usage of the split-GFP technology for the normalization of the expression level of each individual protein variant combined with activity measurements, thus resolving the important problems associated with the different solubility of each mutant and allowing the detection of previously invisible variants. The small size of the employed protein tag (16 amino acids) required for the reconstitution of the GFP fluorescence reduces possible interferences such as enzyme activity variations or solubility disturbances to a minimum. Specific enzyme activity measurements without purification, in situ soluble protein expression monitoring, and data normalization are the powerful outputs of this methodology, thus enabling the accurate identification of improved protein variants during high-throughput screening by substantially reducing the occurrence of false negatives and false positives., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This article reviews recent advances in the design and discovery of inert metal complexes as protein binders. In these metal-based probes or drug candidates, the metal is supposed to exert a purely structural role by organizing the coordinating ligands in the three dimensional space to achieve a shape and functional group complementarity with the targeted protein pockets. Presented examples of sandwich, half-sandwich and octahedral d(6)-metal complexes reinforce previous perceptions that metal complexes are highly promising scaffolds for the design of small-molecule protein binders and complement the molecular diversity of organic chemistry by opening untapped chemical space., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Our goal was to validate an educational 90-min minicourse in lower-irradiating cardiac invasive techniques., Background: Despite comprehensive radiation safety programs, patient radiation exposure in invasive cardiology remains considerable., Methods: Before and at a median period of 3.7 months after the minicourse at 32 German cardiac centers, 177 interventionalists consistently documented radiation parameters for 10 coronary angiographies: dose area product (DAP), radiographic and fluoroscopic fractions, fluoroscopy time, and number of radiographic frames and runs., Results: A total of 154 cardiologists attended the minicourse and achieved significant (p < 0.001) decrease in patients' median overall DAP (-48.4%), from baseline 26.5 to 13.7 Gy × cm(2). They reduced fluoroscopy times (-20.8%), radiographic runs (-9.1%), frames/run (-18.6%) and frames (-29.6%), and both radiographic DAP/frame (-27.4%) and fluoroscopic DAP/s (-39.3%), which indicate improved collimation, reduced-irradiation angulations, or adequate image quality. Dose-related parameters for the remaining 23 invited cardiologists unable to attend the workshop did not change significantly in univariate comparison. Multilevel analysis (p < 0.001) confirmed the efficacy of the minicourse itself (-14.7 Gy × cm(2)) and revealed higher DAP for increasing body mass index (+1.5 Gy × cm(2) per kg/m(2)), male sex (+5.8 Gy × cm(2)), age (+1.5 Gy × cm(2)/decade), and-owing to different settings during image acquisition-for advanced flat-panel detector systems (+9.0 Gy × cm(2)) versus older, traditional image intensifier systems., Conclusions: Despite significant required training in radiation safety for all interventional cardiologists, the presented additional 90-min minicourse significantly reduced patient dose., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The effects of smoking on central aortic pressures and the age-related increase in left ventricular mass (LVM) are largely unknown. We studied the relationship between smoking, arterial distensibility, central aortic pressures and left ventricular mass in two population-based studies., Methods: Data was obtained from two German population-based studies (KORA and SHIP, participants' ages 25-84 years). We identified 114 normotensive current smokers and 185 normotensive all-time non-smokers in KORA as well as 400 and 588 such individuals in SHIP. Echocardiographic LVM was obtained at baseline (T0) and follow-up after ten years (T1) in KORA and at follow-up (T1) in SHIP. Additionally, pulse-wave analysis-based central aortic pressure and augmentation index (AIx) were measured at T1 in KORA., Results: Cross-sectional analysis, using KORA T0 and SHIP T1, revealed in both studies a higher covariate-adjusted LVM and left ventricular mass index (LVMI) in smokers as compared with non-smokers. Moreover, in the KORA T1 examination, the smokers demonstrated a more pronounced increase, relative to baseline, of LVM (+13.5%) and LVMI (+13.4%) compared to non-smokers (+8.59% and +8.65%; p=0.036 and 0.042, respectively). Additionally, at KORA T1 smokers had a higher central systolic blood pressure and higher AIx than non-smokers (p=0.012 and p=0.001, respectively)., Conclusions: The difference in central aortic pressure due to enhanced and more prolonged wave reflection may explain our finding of a further pronounced increase in left ventricular wall thickness and mass over time in smokers., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The impact of white blood cell count (WBCc) on the outcome of patients with non-ischemic left ventricular (LV) dysfunction is unknown. In the present study we investigated the influence of WBCc on mortality and cardiac inflammation in patients with reduced LV systolic function in the absence of ischemic or valvular etiology., Methods and Results: We included 381 patients with reduced left ventricular (LV) ejection fraction (LVEF ≤ 45%) quantified by two-dimensional echocardiography. Coronary artery disease and valvular diseases were excluded by angiography and echo, respectively, in all patients. WBCc was quantified routinely upon first hospital admission. In 291 patients, endomyocardial biopsies from the right ventricle were performed upon first hospital admission for assessment of cardiac inflammation. Follow-up was up to 5.5 years (median 2.93 [1.7;4.0]). Information on vital status of patients was obtained from official resident data files. WBCc >11 Gpt/l was associated with significantly increased mortality in patients with severe LV dilation (end-diastolic diameter (LVEDD) >70 mm quantified by echocardiography) in comparison to patients showing WBCc ≤ 11 Gpt/l (41.7% vs 13.6%, p=0.02). Multivariable Cox regression analysis showed that WBCc predicts mortality independently of other cardiovascular risk factors and LVEF (hazard ratio 1.14; p=0.04). Doses of heart failure medication did not differ significantly in patients with LVEDD >70 mm and WBCc >11 Gpt/l when compared to LVEDD >70 mm and WBCc ≤ 11 Gpt/l (percent of maximum doses: ß-blockers p=0.51, ACE inhibitors p=0.56, AT1 antagonists p=0.77, aldosterone antagonists p=0.35). WBCc including its subpopulations (monocytes, lymphocytes and granulocytes) did not show a significant correlation with cardiac amounts of CD3(+)-lymphocytes (r=0.02, p=0.78) or CD68(+)-macrophages (r=1.0, p=0.09) (n=291)., Conclusion: WBCc at first hospital admission predicts long term-mortality in patients with dilated cardiomyopathy independently of cardiovascular risk factors., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular disease in the general population and in patients with chronic kidney disease. The objective of this study was to investigate the association of estimated glomerular filtration rate (eGFR) with left ventricular mass index (LVMI), LVH and left ventricular geometry. A question of clinical relevance is whether estimated glomerular filtration rate based on cystatin C (eGFRcystatinC) is a better marker for cardiovascular risk than estimated glomerular filtration rate based on creatinine (eGFRcreatinine)., Methods: The study sample included 2830 individuals from the population-based Study of Health in Pomerania (SHIP). LVH was defined as echocardiographic LVMI >48 g/m(2.7) in men and >44 g/m(2.7) in women. Kidney function, as assessed by eGFR, was determined from established equations: the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and a cystatin-based multivariable equation., Results: We found an inverse association between eGFR and LVMI. This association was stronger in models with eGFRcystatinC than in models with eGFRcreatinine. Subjects with moderately-to-severely decreased kidney function (defined as eGFR 15-<60 mL/min per 1.73 m(2)) had higher odds for abnormal geometric patterns of the left ventricle than subjects with normal eGFR when eGFRcystatinC was used., Conclusions: The findings suggest that eGFRcystatinC is superior to eGFRcreatinine for assessing the risk of cardiovascular disease., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: A dentition of at least 20 teeth is associated with sufficient masticatory efficiency and is a stated health goal of the World Health Organisation. We examined whether subjects with missing, unreplaced teeth had an increased mortality risk., Methods: We used data prospectively collected from those participants in the population-based Study of Health in Pomerania who had fewer than 20 remaining teeth, resulting in a sample of 1803 participants with a median age of 64 years. Of those, 188 subjects had 9 or more unreplaced teeth. During a median follow-up period of 9.9 years, 362 subjects died, 128 of whom of cardiovascular causes., Results: We found that having 9 or more unreplaced teeth was related to all-cause mortality (rate ratio 1.53, 95% CI: 1.11-2.10; adjusted for variables according to causal diagrams: remaining teeth, age, sex, education, income, marital status, partnership, and oral health behaviour) and cardiovascular mortality (rate ratio 1.94, 95% CI: 1.15-3.25). When adjusting not only for the variables according to causal diagrams but also for smoking, alcohol consumption, physical activity, obesity, hypertension, diabetes, and dyslipidemia, the rate ratio was 1.43 (95% CI: 1.05-1.96) for all-cause mortality and 1.88 (95% CI: 1.10-3.21) for cardiovascular mortality., Conclusions: A reduced, unrestored dentition is associated with increased mortality risk. Thus, clinicians and dietitians have a responsibility to consider individual chewing ability in nutritional recommendations., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Psoriasis has been associated with cardiovascular diseases, but its relationship to markers of subclinical atherosclerosis has not been fully elucidated. The aim of the study is to analyze the association of psoriasis with common carotid artery intima-media thickness (CCA-IMT) and plaque prevalence of the carotid arteries., Methods: Data of 1987 men and women aged 25-88 years from the population-based Study of Health in Pomerania (SHIP) in north-eastern Germany were used. Cross-sectional associations of psoriasis with IMT and carotid plaque prevalence were analyzed using linear and logistic regression models adjusted for relevant confounders (age, sex, smoking, alcohol consumption, waist circumference, physical activity, systolic blood pressure, anti-hypertensive medication, acetylsalicylic acid, HbA(1c), total/HDL cholesterol ratio, lipid-lowering medication)., Results: Psoriasis was associated with mean CCA-IMT, but not with carotid plaque prevalence. Comparisons between subjects with and without psoriasis showed an adjusted mean difference of the CCA-IMT of 0.016 mm (95% confidence interval [CI]: 0.004 mm-0.028 mm, p < 0.01) and an odds ratio for plaque prevalence of 1.12 (95% CI: 0.85-1.47) after adjusting for confounders., Conclusion: Our findings suggest that psoriasis is associated with increased carotid mean IMT and might therefore contribute to the atherosclerotic process and subsequent cardiovascular events., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Previous experimental and patient-based studies suggest that prolactin (PRL) and its 16 kDa fragment influence cardiovascular phenotypes by modulating angiogenesis. The association between serum PRL and cardiac remodeling in the general population is unknown., Methods: We evaluated 804 individuals (441 women) from the population-based Study of Health in Pomerania, aged ≥ 45 years, with available baseline serum PRL who underwent serial echocardiography at baseline and five-year follow-up. Left ventricular mass (LVM) was calculated and left ventricular hypertrophy (LVH) defined by sex-specific distributions of LVM. LV geometry was defined on the basis of relative wall thickness (RWT) and LVH. Sex-specific multivariable regression analyses were performed relating PRL (independent variable modelled as a continuous variable and as sex-specific quartiles) to change in LVM, RWT, and to incident LVH and abnormal geometry., Results: Baseline PRL concentrations were inversely associated with LVM change in men, but not in women (β per 10% decrease in PRL: 0.37; 95% CI, 0.13-0.60 in men and -0.02; 95% CI, -0.21 to 0.17 in women, respectively). In men, baseline PRL concentrations were also inversely associated with incident LVH [first vs. fourth PRL quartile: relative risk (RR) 2.26 (95% CI, 1.20-4.24)] and altered LV geometry on follow-up [RR for incident concentric hypertrophy per 10% decrease in PRL: 1.20 (95% CI, 1.06-1.37)]. None of the longitudinal associations were observed in women., Conclusion: We observed inverse associations of PRL with LVM change, incident LVH, and altered LV geometry in men, but not in women. Additional studies are warranted to confirm our findings and to elucidate the mechanisms underlying these sex-specific associations., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Previous studies reported associations between insulin-like growth factor I (IGF-I) serum concentration and cardiac morbidity and mortality, but the association between IGF-I serum concentration and cardiac repolarization has not been investigated in a population-based study so far. Therefore, we analyzed the impact of IGF-I concentrations on QTc, QT and RR intervals in two population based studies, The Study of Health in Pomerania (SHIP) and the Rotterdam Study., Design: 457 individuals from SHIP and 155 individuals from the Rotterdam Study older than 55 years and without cardiovascular diseases and a left ventricular hypertrophy were investigated. IGF-I was determined by automated two-site chemiluminescence immunoassays and electrocardiograms were recorded by an ACTA electrocardiograph at a sampling frequency of 500 Hz. The association of IGF-I with QTc, QT and RR intervals was investigated by multivariable linear regression analyses adjusted for age, gender, diabetes mellitus, myocardial infarction, hypertension, body mass index, serum potassium and calcium in both studies separately and in pooled analysis., Results: There were no significant associations between log-transformed IGF-I and QTc interval in the single populations, whereas a significant inverse association was detectable in the pooled population (β, -15.6; 95%-confidence interval, -25.7, -5.5). The QTc interval was significantly higher in the first tertile of IGF-I compared to the third tertile (β, 5.4; 95%-confidence interval, 9.5-1.3) in the pooled analysis., Conclusion: The inverse association between IGF-I serum concentrations and QTc interval in our study is suggestive of a higher risk for cardiac arrhythmias and thus might provide additional evidence for increased cardiovascular mortality in subjects with low IGF-I secretion., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men., Methods and Results: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n=330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p=0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p<0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p=0.03)., Conclusions: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Small clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population., Methods: Our study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥ 50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd-4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented., Results: Subjects <50 years with high PAC (OR 1.60; 95% CI 1.07-2.38) or ARR (OR 1.81; 95% CI 1.21-2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07-2.47) or ARR (OR 1.62; 95% CI 1.05-2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥ 50 years., Conclusions: High and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Low serum magnesium (Mg(++)) levels are associated with future development of left ventricular hypertrophy independently of common cardiovascular risk factors, as recently demonstrated in the five-year follow-up of the population-based Study of Health in Pomerania (SHIP). As left ventricular hypertrophy has significant prognostic implications, we hypothesized that serum Mg(++) levels are associated with cardiovascular mortality., Method and Results: All-cause mortality and cardiovascular mortality were analyzed in relationship to serum Mg(++) concentrations at baseline by Cox proportional hazard model in SHIP (n=4203, exclusion of subjects with Mg(++) supplementation). The median duration of mortality follow-up was 10.1 years (25th percentile: 9.4 years, 75th percentile: 10.8 years; 38,075 person-years). During the follow-up, 417 deaths occurred. Mortality in subjects with Mg(++)≤0.73 mmol/l was significantly higher for all-cause deaths (10.95 death per 1000 person years), and cardiovascular deaths (3.44 deaths per 1000 person years) in comparison to higher Mg(++) concentrations (1.45 deaths from all-cause per 1000 person years, 1.53 deaths from cardiovascular cause per 1000 person years). This association remained statistically significant after adjustment for multiple cardiovascular risk factors, including arterial hypertension, and antihypertensive therapy including diuretics (log-rank-test p=0.0001 for all-cause mortality, and p=0.0174 for cardiovascular mortality)., Conclusions: Low serum Mg(++) levels are associated with higher all-cause mortality and cardiovascular mortality. This corresponds well with recent findings that hypomagnesemia is associated with the increase of left ventricular mass over the following years., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Endothelial dysfunction precedes apparent atherosclerosis in humans and is associated 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 the association of serum HbA(1c) levels with endothelial function., Methods: We studied cross-sectional data from 1384 subjects (696 women), aged 25-85, without diabetes, from the population-based Study of Health in Pomerania (SHIP-1). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) measurements of the brachial artery were performed using standardised ultrasound techniques. Linear regression models were carried out to assess the association between serum HbA(1c) levels and FMD/NMD., Results: Multivariable analyses disclosed an inverse association between serum HbA(1c) levels and FMD in women, but not in men. In women without current use of antihypertensive medication, increasing serum HbA(1c) levels were associated with decreasing FMD levels after adjustment for age, body mass index, smoking status, hypertension, low-density lipoprotein cholesterol, and sex-hormone medication (β=-1.17; 95% CI -2.03; -0.30, p=0.009). There was an inverse association between serum HbA(1c) levels and NMD in men (β=-1.68; 95% CI -2.83; -0.52, p=0.005), but not in women., Conclusion: We conclude that higher serum HbA(1c) levels in non-diabetic subjects are inversely associated with FMD in women without antihypertensive medication, but not in men. The gender-specific aspects concerning the association of HbA(1c) levels and NMD in this population should be investigated in further studies. Our results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA(1c) are associated with subclinical cardiovascular diseases detected by FMD, especially in women., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Previous population-based studies provided conflicting results regarding the association of total serum insulin-like growth factor I (IGF-I) and mortality. The aim of the present study was to assess the relation of IGF-I levels with all-cause mortality in a prospective study., Design: DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) is a large, multistage, and nationally representative study of primary care patients in Germany. The study population included 2463 men and 3603 women. Death rates were recorded by the respective primary care physician. Serum total IGF-I levels were determined by chemiluminescence immunoassays and categorized into three groups (low, moderate, and high) according to the sex- and age-specific 10th and 90th percentiles., Results: Adjusted analyses revealed that men with low [hazard ratio (HR) 1.70 (95% confidence interval [CI] 1.05-2.73), p=0.03] and high [HR 1.76 (95% CI 1.09-2.85), p=0.02] IGF-I levels had higher risk of all-cause mortality compared to men with moderate IGF-I levels. The specificity of low IGF-I and high IGF-I levels increased with lower and higher cut-offs, respectively. No such association became apparent in women., Conclusions: The present study revealed a U-shaped relation between IGF-I and all-cause mortality in male primary care patients., (Copyright © 2011 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.)

Objective: This paper introduces the objectives, methods and results of ontology development in the EU co-funded project Advancing Clinico-genomic Trials on Cancer-Open Grid Services for Improving Medical Knowledge Discovery (ACGT). While the available data in the life sciences has recently grown both in amount and quality, the full exploitation of it is being hindered by the use of different underlying technologies, coding systems, category schemes and reporting methods on the part of different research groups. The goal of the ACGT project is to contribute to the resolution of these problems by developing an ontology-driven, semantic grid services infrastructure that will enable efficient execution of discovery-driven scientific workflows in the context of multi-centric, post-genomic clinical trials. The focus of the present paper is the ACGT Master Ontology (MO)., Methods: ACGT project researchers undertook a systematic review of existing domain and upper-level ontologies, as well as of existing ontology design software, implementation methods, and end-user interfaces. This included the careful study of best practices, design principles and evaluation methods for ontology design, maintenance, implementation, and versioning, as well as for use on the part of domain experts and clinicians., Results: To date, the results of the ACGT project include (i) the development of a master ontology (the ACGT-MO) based on clearly defined principles of ontology development and evaluation; (ii) the development of a technical infrastructure (the ACGT Platform) that implements the ACGT-MO utilizing independent tools, components and resources that have been developed based on open architectural standards, and which includes an application updating and evolving the ontology efficiently in response to end-user needs; and (iii) the development of an Ontology-based Trial Management Application (ObTiMA) that integrates the ACGT-MO into the design process of clinical trials in order to guarantee automatic semantic integration without the need to perform a separate mapping process., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Left ventricular hypertrophy (LVH) is a significant predictor of adverse cardiovascular events. Experimental studies suggest a pathophysiological role of magnesium (Mg(2+)) in the development of arterial hypertension and LVH., Methods: In subjects with complete echocardiographic data from the population-based longitudinal "Study of Health in Pomerania" (n=1 348), the difference in left ventricular mass (LVM) over 5 years (echocardiography) was analyzed in relationship to serum Mg(2+) at baseline., Results: Mg(2+) at baseline (0.790 ± 0.003 mmol/l, mean ± SEM) inversely correlated with the difference in LVM over 5 years (p<0.0001, females: p<0.002, males: p<0.024). In the lowest Mg(2+)-quintile (Mg(2+)<=0.73 mmol/l), LVM (187.4 ± 3.1 g at baseline) increased by 14.9 ± 1.2 g, while in the highest Mg(2+)-quintile (Mg(2+)>=0.85 mmol/l) LVM (186.7 ± 3.4 g at baseline) decreased by -0.5 ± 2.8 g (p<0.0001 between quintiles). By multivariable analysis including several cardiovascular risk factors and antihypertensive treatment, serum Mg(2+) was associated with the increase in LVM at a statistically high significant level (p<0.0001). LVM after 5 years was significantly higher in subjects within the lower Mg(2+)-quintiles. This association remained highly significant after adjustment for several cardiovascular risk factors including arterial hypertension and diabetes mellitus., Conclusions: Hypomagnesemia is one of the strongest predictors of gain in LVM over the following 5 years., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population., Materials and Methods: From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO₂@AT), peak exercise (peakVO₂), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed., Results: At peak exercise performance, in women IGF-I showed significant associations to peakVO₂ and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO₂@AT in both genders., Conclusion: Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores., (Copyright © 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.)

Objective: Chronic kidney disease, at least in its advanced stages, can be regarded as a non-traditional cardiovascular risk factor. The purpose of this study was to evaluate whether early stages of renal dysfunction are associated with flow-mediated vasodilatation, as an early marker of the atherosclerotic disease process., Methods: In 1515 subjects (753 females) from the population-based Study of Health in Pomerania, the relationship between flow-mediated vasodilatation of the brachial artery (cuff occlusion of the forearm for 5 min) and glomerular filtration rate, estimated on the basis of serum cystatin C levels, was analyzed under consideration of various cardiovascular risk factors., Results: Flow-mediated vasodilatation was 5.75 + or - 0.16% in women and 4.29+/-0.12% in men (mean + or - SEM). Glomerular filtration rate amounted to 94.2 + or - 0.7 ml/min/1.73 m(2), with 8.1% subjects with glomerular filtration rate < or = 60 ml/min/1.73 m(2). Flow-mediated vasodilatation significantly correlated with glomerular filtration rate in the entire population (r=0.237, p<0.001), in women (r=0.224, p<0.001) and in men (r=0.168, p<0.001). Adjusting for age and multiple cardiovascular risk factors and also for high-sensitive C-reactive protein levels revealed a significant association of flow-mediated vasodilatation and glomerular filtration rate in women (p=0.01), but not in men, with similar results when the analyses were restricted to individuals with glomerular filtration rate >60 ml/min/1.73 m(2)., Conclusion: Mild reduction in renal function is associated with alterations in endothelial function in females. Hence, very mild alterations in kidney function may also be regarded as a cardiovascular risk factor at least in women., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

There is increasing evidence that urinary albumin excretion, even when below the accepted threshold values for normal excretion, may have significant impact on future cardiovascular risks. To further define this, a total of 1086 patients, aged 45 years and older from the population-based, longitudinal 'Study of Health in Pomerania' were evaluated. Patients had echocardiographic analysis at baseline and 5-year follow-up, and were grouped into quartiles according to their baseline urinary albumin-to-creatinine ratio. At baseline, left ventricular mass in the first three quartiles was similar; however, the fourth quartile was significantly elevated and further increased over the 5-year follow-up. In the first quartile, the albumin-to-creatinine ratio and left ventricular mass did not significantly change over 5 years. In the second and third quartiles, the left ventricular mass progressively increased and was significantly correlated with the albumin-to-creatinine ratio. In multivariable analysis, this association was independent of other common cardiovascular risk factors and applicable to both genders. Our study found that the urinary albumin-to-creatinine ratio, even below the current threshold for definition of microalbuminuria, is significantly associated with increased left ventricular mass.

Objectives: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) might predict future adverse events. We undertook the present study to investigate the association of AVS and MAC with all-cause and cardiovascular mortality. We further studied whether a combined presence of AVS and MAC is more strongly associated with mortality than the single items and sought to disclose possible gender differences in the investigated associations., Methods: We used data from 2081 participants aged > or =45 years (1063 women) of the Study of Health in Pomerania (SHIP). AVS and MAC were determined echocardiographically, and a heart valve sclerosis score was calculated by summing up the AVS and MAC variables. The median duration of mortality follow-up was 8.6 years (17,162 person-years)., Results: There were 528 subjects (25.4%) with isolated AVS, 35 with isolated MAC (1.7%) and 89 with both AVS and MAC (4.3%). A total number of 228 deaths (11.0%) occurred during follow-up, including 133 (21.6%) with AVS and 95 subjects (6.5%) without AVS (incidence rate ratio 3.49, 95% CI 2.77; 4.40, p<0.001). Likewise, mortality rates were higher for subjects with MAC than subjects without MAC (incidence rate ratio 3.79, 95% CI 2.82; 5.02, p<0.001). Multivariable analyses revealed that the associations of AVS and MAC with all-cause and cardiovascular mortality were independent of major confounders and strongest for highest values of the heart valve sclerosis score. AVS-related mortality was more pronounced in women than in men., Conclusion: AVS and MAC are associated with all-cause and cardiovascular mortality. The association between AVS and mortality is gender-specific with women with AVS being at a higher mortality risk than men with AVS. The summation of AVS and MAC to a heart valve sclerosis score improves the predictability with respect to mortality., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Pulmonary hypertension is a relevant interceding morbidity in patients with pulmonary fibrosis that has significant impact on exercise tolerance and outcome. The aim of this study was to further characterize the exercise intolerance, dyspnoea and ventilatory inefficiency of patients with pulmonary fibrosis in the presence or absence of pulmonary hypertension via cardiopulmonary exercise testing. Thirty-four patients underwent pulmonary function testing, symptom-limited exercise testing on a bicycle and dyspnoea evaluation according to the BORG scale. Pulmonary hypertension was assessed by echocardiography and in a subset of patient's right heart catheterization. Sixteen of 34 patients with pulmonary fibrosis revealed pulmonary hypertension. While all study patients did not differ in lung functions and demographic characteristics, patients suffering from pulmonary hypertension showed a significantly impaired exercise tolerance and worsened ventilatory inefficiency. The extent of pulmonary artery pressure elevation impacted significantly on ventilatory inefficiency. In addition, the increased ventilatory requirements significantly influenced the extent of dyspnoea in patients with pulmonary hypertension. We conclude that pulmonary hypertension has a significant impact on exercise capacity and dyspnoea in patients with interstitial lung disease (ILD). The further impairment of exercise capacity as well as the extent of dyspnoea in patients with interceding PHT is attributable to a significantly impaired ventilatory inefficiency.

Objectives: We tested the hypothesis that working shifts is related to atherosclerosis and myocardial infarction., Background: The number of shift workers is continuously increasing. Shift work is discussed to be related with cardiovascular heart disease., Methods: A total of 2510 subjects recruited for the population-based Study of Health in Pomerania were tested, 698 of whom were former shift workers. A general population sample was examined to reach generalizibility and to produce results independent from the effects of the personal shift schedule and from the specific working conditions. Carotid ultrasound was performed to evaluate carotid intima-media thickness. We used multivariable analyses to estimate the coronary heart disease risk, adjusted for age, sex and atherosclerotic risk factors, stratified by exposure to shift work and its duration., Results: Atherosclerotic risk factors differed in part between shift workers and non-shift workers. Shift work was associated with atherosclerosis and myocardial infarction, depending on the duration of the exposure and the age of the participants. Multivariable Cox regression analysis identified shift work as a risk factor for myocardial infarction to be manifest at younger ages (adjusted hazard ratio 1.53, 95% CI 1.06-2.22)., Conclusions: Exposure to shift work is a risk factor for atherosclerosis and myocardial infarction. Special prevention programs for shift workers should be provided.

Background: Displacement of plaque is a major concern during coronary intervention of ostial bifurcation lesions. For this reason, angioplasty involves complex stenting procedures, which may trigger development of restenosis in a previously non-diseased parent vessel., Objectives: To examine, whether plaque displacement may be prevented by scoring atherosclerotic plaque with a cutting-balloon (CB) stand-alone procedure., Methods: Data of patients with Duke E and B type ostial bifurcation lesions (>/=70% stenosis involving a diagonal and/or marginal branch >2 mm deriving from a non-diseased parent vessel), who were treated with CB as stand-alone procedure within the prospective NICECUT multicenter trial were analyzed. Primary endpoint was the rate of binary stenosis and target lesion revascularization (TLR). Secondary endpoints were procedural success and major adverse cardiac events (MACE) at 6-months follow-up., Results: 63 out of 65 lesions (56 patients) were successfully amenable to treatment with CB (96.4% procedural success). 76.9% of patients were successfully treated with CB as a stand-alone procedure, while provisional stenting was necessary in 23.1%. At follow-up, binary stenosis was found in 23.2%, among the total population. Total rate of TLR and MACE were 7.7% and 3.6%, respectively, compared to 4.0% and 2.0% in patients for whom CB stand-alone procedure was feasible, while it was 20.0% and 6.7% for stented lesions., Conclusions: CB angioplasty as a stand-alone procedure may facilitate interventional treatment of ostial bifurcation lesions and may help to avoid complex stenting procedures. It is associated with a low rate of binary stenosis and TLR.