Showing papers by "Marcus Dörr published in 2015"

Association of Cardiometabolic Multimorbidity With Mortality

Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Directional dominance on stature and cognition in diverse human populations

Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Directional dominance on stature and cognition in diverse human populations

Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

A meta-analysis of gene expression signatures of blood pressure and hypertension

Abstract: Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

Longitudinal effects of systemic inflammation markers on periodontitis.

Abstract: Aim Systemic low-grade inflammation represents a central hallmark of chronic diseases and has been proposed as the underlying mechanism linking factors like obesity or diabetes with periodontitis. However, the impact of inflammatory markers on periodontitis has not yet been investigated. Materials and Methods The study population comprised 1784 subjects from the Study of Health in Pomerania with complete 11-year follow-up. Fibrinogen and white blood cell (WBC) counts were measured as markers of inflammation. Periodontitis was assessed by probing depth (PD), clinical attachment loss (CAL) and the CDC/AAP case definition. Results Multilevel regression analyses revealed significant coefficients for the impact of both inflammation markers on the percentage of sites with PD/CAL ≥ 3 mm. Increases in fibrinogen about 1 g/l were associated with 3.0% and 2.7% more sites with PD/CAL ≥ 3 mm respectively. Consistent associations were found using mean values of PD/CAL but not using missing teeth or caries. Regarding the CDC/AAP case definition, 11-year changes in fibrinogen and WBC counts were significantly associated with ≥1 category progression (OR: 1.36 and 1.11). Conclusions Fibrinogen levels and WBC counts showed consistent long-term associations with PD, CAL and the CDC/AAP case definition. Results indicate that systemic low-grade inflammation might indeed represent one possible pathway for effects of obesity, diabetes or other chronic inflammatory conditions on periodontitis.

Endogenous Androgens and Sex Hormone-Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes.

Abstract: Context and Objectives: The association of endogenous androgens and sex hormone–binding globulin (SHBG) with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) mostly 23562 refers to small and selected study samples with immunoassay-based measurements. Thus, we investigated the association of hormone levels with MetS and T2DM in women from a large population-based sample. Design, Setting, and Participants: A total of 2077 women from the Study of Health in Pomerania were assessed at baseline (N = 3160, 1997–2001) and 5-year follow-up (N = 1711, 2002–2006). Main Outcomes and Measures: We investigated associations of total testosterone (T) and androstenedione measured by liquid chromatography-tandem mass spectrometry, SHBG by immunoassay, and free T and free androgen index with MetS and T2DM. Results: Baseline prevalence of MetS and T2DM was 23.1% (N = 365) and 9.5% (N = 196), with an incidence of 17.7 and 7.0 per 1.000 person-years, respectively. Cross-sectional analyses yielded inverse associati...

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Abstract: Background: During the last two decades, it has become obvious that 3,5-diiodothyronine (3,5-T2), a well-known endogenous metabolite of the thyroid hormones thyroxine (T4) or triiodothyronine (T3), not only represents a simple degradation intermediate of the former but also exhibits specific metabolic activities. Administration of 3,5-T2 to hypothyroid rodents rapidly stimulated their basal metabolic rate, prevented high-fat diet-induced obesity as well as steatosis, and increased oxidation of long-chain fatty acids. Objective: The aim of the present study was to analyze associations between circulating 3,5-T2 in human serum and different epidemiological parameters, including age, sex, or smoking, as well as measures of anthropometry, glucose, and lipid metabolism. Methods: 3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania. Subsequently, analysis of variance and multivariate linear regression a...

Immunoadsorption therapy in dilated cardiomyopathy

Abstract: Dilated cardiomyopathy is a common myocardial disease characterized by ventricular chamber enlargement and systolic dysfunction that result in heart failure. In addition to genetic predisposition, viral infection and myocardial inflammation play a causal role in the disease process of dilated cardiomyopathy. Experimental and clinical studies suggest that activation of the humoral immune system, with production of circulating cardiac autoantibodies, plays an important functional role in the development and progression of cardiac dysfunction in patients with dilated cardiomyopathy. Small open-controlled studies showed that removal of circulating antibodies by immunoadsorption results in improvement of cardiac function and decrease in myocardial inflammation. At present, immunoadsorption is an experimental treatment option for improvement of cardiac function - therapy that calls for confirmation by a placebo-controlled multicenter study.

De Novo Acute Heart Failure and Acutely Decompensated Chronic Heart Failure

Abstract: Background Heart failure is one of the most common diseases of adults in Europe, with an overall prevalence of 1-2%. Among persons aged 60 and above, its prevalence is above 10% in men and 8% in women. Acute heart failure has a poor prognosis; it is associated with a high rate of rehospitalization and a 1-year mortality of 20-30%. Methods This review is based on pertinent literature, including guidelines, retrieved by a selective search in PubMed. Results There are different types of acute heart failure; the basic diagnostic assessment is performed at once and consists of ECG, echocardiography, and the measurement of N-terminal pro-brain natriuretic peptide (NTproBNP) and troponin levels. The most common causes of decompensation are arrhythmia, valvular dysfunction, and acute cardiac ischemia, each of which accounts for 30% of cases. The potential indication for immediate revascularization should be carefully considered in cases where acute heart failure is due to coronary heart disease. The basic treatment of acute heart failure is symptomatic, with the administration of oxygen, diuretics, and vasodilators. Ino-tropic agents, vasopressors, and temporary mechanical support for the circulatory system are only used to treat cardiogenic shock. Conclusion The treatment of acute heart failure is markedly less evidence-based than that of chronic heart failure. Newer treatment approaches that are intended to improve outcomes still need to be tested in multicenter trials.

Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association With the Kininogen 1 and Prekallikrein Genes

Abstract: Background—The renin–angiotensin–aldosterone system (RAAS) is critical for regulation of blood pressure and fluid balance and influences cardiovascular remodeling. Dysregulation of the RAAS contrib...

Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts

Abstract: Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D.

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

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.

Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis The Study of Health in Pomerania (SHIP)

Abstract: Objective—In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population. Approach and Results—We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS w...

Characteristics associated with non-participation in 7-day accelerometry

Abstract: Objective To assess levels of physical activity the use of objective physical activity measures like accelerometers is promising. We investigated characteristics associated with non-participation in accelerometry within an apparently healthy sample.

Assessing cutoff values for increased exercise blood pressure to predict incident hypertension in a general population.

Abstract: OBJECTIVE Cutoff values for increased exercise blood pressure (BP) are not established in hypertension guidelines. The aim of the study was to assess optimal cutoff values for increased exercise BP to predict incident hypertension. METHODS Data of 661 normotensive participants (386 women) aged 25-77 years from the Study of Health in Pomerania (SHIP-1) with a 5-year follow-up were used. Exercise BP was measured at a submaximal level of 100 W and at maximum level of a symptom-limited cycle ergometry test. Cutoff values for increased exercise BP were defined at the maximum sum of sensitivity and specificity for the prediction of incident hypertension. The area under the receiver-operating characteristic curve (AUC) and net reclassification index (NRI) were calculated to investigate whether increased exercise BP adds predictive value for incident hypertension beyond established cardiovascular risk factors. RESULTS In men, values of 160 mmHg (100 W level; AUC = 0.7837; NRI = 0.534, P < 0.001) and 210 mmHg (maximum level; AUC = 0.7677; NRI = 0.340, P = 0.003) were detected as optimal cutoff values for the definition of increased exercise SBP. A value of 190 mmHg (AUC = 0.8347; NRI = 0.519, P < 0.001) showed relevance for the definition of increased exercise SBP in women at the maximum level. CONCLUSION According to our analyses, 190 and 210 mmHg are clinically relevant cutoff values for increased exercise SBP at the maximum exercise level of cycle ergometry test for women and men, respectively. In addition, for men, our analyses provided a cutoff value of 160 mmHg for increased exercise SBP at the 100 W level.

L-Arginine and SDMA Serum Concentrations Are Associated with Subclinical Atherosclerosis in the Study of Health in Pomerania (SHIP).

Abstract: Objective Even though ˪-arginine (ARG) derivatives can predict cardiovascular mortality, their role as atherosclerotic biomarkers is unclear. We tested the hypothesis if asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and the sum of both (DMA) are positively, while ARG and ARG/ADMA ratio are inversely associated with carotid intima-media thickness (cIMT) and atherosclerotic plaque in the carotid artery.

Multicenter long-term validation of a minicourse in radiation-reducing techniques in the catheterization laboratory.

Abstract: Patient radiation exposure in invasive cardiology is considerable. We aimed to investigate, in a multicenter field study, the long-term efficacy of an educational 90-minute workshop in cardiac invasive techniques with reduced irradiation. Before and at a median period of 2.5 months and 2.0 years after the minicourse (periods I, II, and III, respectively) at 5 German cardiac centers, 18 interventionalists documented various radiation parameters for 10 coronary angiographies. The median patient dose area product (DAP) for periods I, II, and III amounted to 26.6, 12.2, and 9.6 Gy × cm 2 , respectively. The short-term and long-term effects were related to shorter median fluoroscopy times (180, 138, and 114 seconds), fewer radiographic frames (745, 553, and 417) because of fewer (11, 11, and 10) and shorter (64, 52, and 44 frames/run) runs, consistent collimation, and restriction to an adequate image quality; both radiographic DAP/frame (27.7, 17.3, and 18.4 mGy × cm 2 ) and fluoroscopic DAP/second (26.6, 12.9, and 14.9 mGy × cm 2 ) decreased significantly. Multivariate analysis over time indicated increasing efficacy of the minicourse itself (−55% and −64%) and minor influence of interventionist experience (−4% and −3% per 1,000 coronary angiographies, performed lifelong until the minicourse and until period III). In conclusion, autonomous self-surveillance of various dose parameters and feedback on individual radiation safety efforts supported the efficacy of a 90-minute course program toward long-lasting and ongoing patient dose reduction.

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

Abstract: 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 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.

Exercise training as a key component of heart failure therapy

Abstract: Physical exercise has been recognized as a standard therapy in the guidelines for secondary prevention of chronic heart failure. In clinical practice its benefits are widely underestimated. It is still too rarely applied as a therapeutic component, despite overwhelming scientific evidence, including meta-analyses illustrating the positive effect on exercise capacity, quality of life and hospitalization. It is crucial that patients undergo a thorough clinical investigation, including exercise testing and are in a clinically stable condition for at least 6 weeks under optimal guideline-conform medicinal therapy before exercise training is initiated. Moreover, it is important that only approved exercise regimens should be prescribed and exercise sessions should be appropriately monitored. Both moderate continuous endurance training and recently developed interval training have been shown to be safe and effective in chronic heart failure. Ideally, endurance training should be combined with moderate resistance training. Current evidence clearly demonstrates a dose-response relationship in the way that beneficial effects of exercise training are strongly related to factors such as exercise duration and intensity. Development of strategies that support long-term adherence to exercise training are a crucial challenge for both daily practice and future research.

Role of Experience, Leadership and Individual Protection in the Cath Lab--A Multicenter Questionnaire and Workshop on Radiation Safety.

Abstract: Purpose: Radiation exposure in invasive cardiology remains considerable We evaluated the acceptance of radiation protective devices and the role of operator experience, team leadership, and technical equipment in radiation safety efforts in the clinical routine Materials and Methods: Cardiologists (115 from 27 centers) answered a questionnaire and documented radiation parameters for 10 coronary angiographies (CA), before and 31 months after a 90-min mini-course in radiation-reducing techniques Results: Mini-course participants achieved significant median decreases in patient dose area products (DAP: from 266 to 130 Gy × cm2), number of radiographic frames (– 29 %) and runs (– 18 %), radiographic DAP/frame (– 32 %), fluoroscopic DAP/s (– 39 %), and fluoroscopy time (– 16 %) Multilevel analysis revealed lower DAPs with decreasing body mass index (– 14 Gy × cm2 per kg/m2), age (– 12 Gy × cm2/decade), female sex (– 59 Gy × cm2), participation of the team leader (– 94 Gy × cm2), the mini-course itself (– 161 Gy × cm2), experience (– 07 Gy × cm2/1000 CAs throughout the interventionalist’s professional life), and use of older catheterization systems (– 66 Gy × cm2) Lead protection included apron (100 %), glass sheet (95 %), lengthwise (94 %) and crosswise (69 %) undercouch sheet, collar (89 %), glasses (28 %), cover around the patients’ thighs (19 %), foot switch shield (7 %), gloves (3 %), and cap (1 %) Conclusion: Radiation-protection devices are employed less than optimally in the clinical routine Cardiologists with a great variety of interventional experience profited from our radiation safety workshop – to an even greater extent if the interventional team leader also participated Key Points: • Radiation protection devices are employed less than optimally in invasive cardiology • The presented radiation-safety mini-course was highly efficient • Cardiologists at all levels of experience profited from the mini-course – considerably more so if the team leader also took part • Interventional experience was less relevant for radiation reduction • Consequently both fellows and trainers should be encouraged to practice autonomy in radiation safety Citation Format: • Kuon E, Weitmann K, Hoffmann W et al Role of Experience, Leadership and Individual Protection in the Cath Lab – A Multicenter Questionnaire and Workshop on Radiation Safety Fortschr Rontgenstr 2015; 187: 899 – 905

The Meaning of “Individualized Medicine”: A Terminological Adjustment of a Perplexing Term

Abstract: This chapter introduces “Individualized Medicine” as a technical term. In order to do this the chapter first gives a precise, logical and conceptual analysis of relevant explanations and definitions from English and German speaking areas. It secondly presents a definition according to which the term “Individualized Medicine” should be used for describing research approaches and health care practices, when the biomarker-based prediction of (a) diseases and/or (b) the effectiveness of therapies by stratification is central. The relevant terms “research approach”, “health care practice”, “biomarker”, “prediction” and “stratification” will be discussed in detail. Finally the term “Individualized Medicine” will be examined regarding its extension and be compared to “Personalized Medicine”, which is also understood terminologically.

Riociguat and cinaciguat exert no direct effects on contractility and relaxation of cardiac myocytes from normal rats

Abstract: Clinical background In the clinical setting, administration of organic nitrates and nitric oxide (NO) donors has serious limitations such as resistance to NO and organic nitrates due to insufficient biometabolism and development of tolerance following prolonged administration of NO soluble guanylate cyclase (sGC) to NO [1,2]. This circumstance has led to development of heme-dependent sGC stimulators and heme-independent sGC activators. The sGC stimulator riociguat and the sGC activator cinaciguat have been shown to induce various beneficial effects in both experimental and clinical research. Any direct dosedependent effects of these compounds on cell contraction and relaxation of isolated cardiac myocytes, however, remain to be elucidated [3].

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

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 <0.3 mIU/l or with a TSH ≥3.0 mIU/l had no significantly different ABI values in comparison with individuals with a TSH in the reference range. Analyses regarding TSH within the reference range or serum 3,5-T2 concentrations did not reveal consistent significant associations with the ABI. No sex-specific associations were detected. Conclusions: The results of our study do not substantiate evidence for an association between thyroid function and PAD, but further studies are needed to investigate the associations of overt forms of thyroid dysfunction with PAD.

Use of Biomarkers for the Prediction of Treatment Response: Immunoadsorption in Dilated Cardiomyopathy as a Clinical Example

Abstract: In this chapter, we outline a clinical example illustrating how integrated analyses of biomarkers might be used for the prediction of treatment response. We report findings from a pilot study that investigated the hemodynamic effects of a novel treatment option, immunoadsorption with subsequent IgG substitution (IA/IgG), in patients with dilated cardiomyopathy. Several previous studies have shown that this treatment leads to a significant improvement of cardiac function and relief of symptoms. Response to this therapy is, however, characterized by a wide inter-individual variability. In a pilot study, we tested the value of clinical, biochemical and molecular parameters for prediction of the response to IA/IgG. This study demonstrated that combined assessment of two markers (negative inotropic activity of antibodies in the blood and gene expression patterns derived from myocardial biopsies) predicts response to this therapy with an extremely high sensitivity and specificity, thereby enabling appropriate selection of patients who most likely benefit from this therapeutic intervention. Further studies will screen for biomarker signatures in blood, which do not depend on endomyocardial biopsies, and will compare responders and non-responders with respect to other molecular markers (e.g. plasma proteome, metabolome and microRNA profiles as well as whole blood transcriptome signatures). In the future, such strategies might facilitate selection of patients with dilated cardiomyopathy who are responders not only to immunoadsorption therapy but also to other heart failure treatments for which a heterogeneous response is observed and thus will help to offer more effective treatments to affected patients.

Is there a male-specific effect on hypertension?

Abstract: First, the KARE data consist of two cohorts, one from rural Ansung and one from urban Ansan. In the non-genetic analysis, the variable indicating region is significantly associated with hypertension (p = 2.1 × 10−22) with an effect size of OR = 1.86 (1.64, 2.11) (main article, Table 1). However, this variable is not included in this analysis (‘‘... data were adjusted for age, sex, and BMI.’’, p. 313, col. 1, line 5). Results are therefore likely influenced by population stratification. Second, the authors did not adequately adjust for multiple testing. In this study, 12 genome-wide analyses were conducted in total: one in the overall population and 11 in subgroups according to age and gender. Furthermore, the authors tested the three different genetic models additive, dominant and recessive in all their analyses, which also To the editor,