Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

The effect of spironolactone on diastolic function in haemodialysis patients.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF > 50%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m2 vs. 1.7 ± 14.1 ml/m2, p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m2 vs. + 2.7 ± 15.9 g/m2; p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012).

The use of tissue-engineered skin to demonstrate the negative effect of CXCL5 on epidermal ultraviolet radiation-induced cyclobutane pyrimidine dimer repair efficiency.

BACKGROUND: Ultraviolet radiation (UVR) is responsible for keratinocyte cancers through the induction of mutagenic cyclobutane pyrimidine dimers (CPDs). Many factors influence CPD repair in epidermal keratinocytes, and a better understanding of those factors might lead to prevention strategies against skin cancer. OBJECTIVES: To evaluate the impact of dermal components on epidermal CPD repair efficiency and to investigate potential factors responsible for the dermal-epidermal crosstalk modulating UVR-induced DNA damage repair in keratinocytes. METHODS: A model of self-assembled tissue-engineered skin containing human primary keratinocytes and fibroblasts was used in this study. RESULTS: We showed that CPD repair in keratinocytes is positively influenced by the presence of a dermis. We investigated the secretome and found that the cytokine CXCL5 is virtually absent from the culture medium of reconstructed skin, compared with media from fibroblasts and keratinocytes alone. By modulating CXCL5 levels in culture media of keratinocytes, we have shown that CXCL5 is an inhibitor of CPD repair. CONCLUSIONS: This work outlines the impact of the secreted dermal components on epidermal UVR-induced DNA damage repair and sheds light on a novel role of CXCL5 in CPD repair.

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

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

Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Pitfalls in accelerometer-based measurement of physical activity: The presence of reactivity in an adult population.

When a behavior is monitored, it is likely to change, even if no change may be intended. This phenomenon is known as measurement reactivity. We investigated systematic changes in accelerometer-based measures over the days of monitoring as an indicator of measurement reactivity in an adult population. One hundred seventy-one participants from the general population (65% women; mean age = 55 years, range: 42-65 years) wore accelerometers for 7 consecutive days to measure sedentary behavior and physical activity (PA). Latent growth models were used (a) to investigate changes in accelerometer wear time over the measurement days and (b) to identify measurement reactivity indicated by systematic changes in sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Over the measurement days, participants reduced accelerometer wear time by trend (rate of change [b] = -4.7 min/d, P = .051, Cohen's d = .38), increased ST (b = 2.4 min/d, P = .018, d = .39), and reduced LPA (b = -2.4 min/d, P = .015, d = .38). Participants did not significantly reduce MVPA (P = .537). Our data indicated that accelerometry might generate reactivity. Small effects on ST and LPA were found. Thus, the validity of accelerometer-based data on ST and LPA may be compromised. Systematic changes observed in accelerometer wear time may further bias accelerometer-based measures. MVPA seems to be less altered due to the presence of an accelerometer.

Hyperthyroxinemia is positively associated with prevalent and incident type 2 diabetes mellitus in two population-based samples from Northeast Germany and Denmark.

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.

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

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

The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies.

OBJECTIVE: It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS) parameters at the heel with the carotid artery intima-media thickness (IMT), the presence of carotid artery plaques, and the ankle-brachial index (ABI). METHODS: The study population comprised 5680 men and women aged 20-93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP) and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. RESULTS: Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. CONCLUSIONS: Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

Ankle-brachial index and peripheral artery disease are not related to restless legs syndrome.

OBJECTIVE: Our aim was to investigate the relationship between impaired peripheral arterial circulation as measured by ankle-brachial index (ABI) and restless legs syndrome (RLS) in the general population. METHODS: Data are derived from three independent, German population-based, prospective studies: the control sample of BiDirect (N = 966), the second follow-up of SHIP (N = 2333), and a subsample of SHIP-Trend (N = 1269). RLS was assessed with questions based on the RLS minimal criteria. ABI was measured with an automated method in BiDirect and with Doppler ultrasound in both SHIP studies. An ABI score below 0.9 was indicative of peripheral arterial disease (PAD). Co-morbidities, medications and behavioural factors were self-reported. Additional measurements included body mass index and haemoglobin from blood serum. For BiDirect, a follow-up with identical methodology was performed after a median of 2.5 years. RESULTS: In cross-sectional analyses, decreased ABI was not significantly associated with RLS as outcome in multivariable logistic regression models adjusted for several potential confounders (BiDirect: odds ratio (OR) = 1.07 for a -0.1 change in ABI, 95% confidence interval (CI): 0.81-1.42, p = 0.62; SHIP-2: OR = 0.99, CI: 0.85-1.16, p = 0.94; SHIP-Trend: OR = 0.99, CI: 0.87-1.13, p = 0.88). Similar non-significant results were achieved using PAD (instead of ABI) as an independent variable. In BiDirect, baseline ABI was not a significant predictor of incident RLS in longitudinal analysis (OR = 0.77, CI: 0.53-1.12, p = 0.17). CONCLUSION: Results from three independent studies suggest that reduced ABI is not a risk factor for RLS in the general population.

[Lung Health Data of the Study of Health in Pomerania - a Review of Samples, Methods and First Results]. / Pneumologisch relevante Daten aus der "Study of Health in Pomerania" (SHIP) ­ eine Übersicht zu den Kohorten, Methoden und ersten Ergebnissen.

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.

[Soliciting Job Centre Clients for a Cardiopreventive Health Examination Programme]. / Gewinnung von Jobcenter-Klienten für die Teilnahme an einem kardiopräventiven Untersuchungsprogramm.

Aim: There is limited knowledge about the reaching of socioeconomic disadvantaged groups for prevention measures. Results of proactive contacting are presented for a 2-step cardiopreventive health examination programme (CHP) in 2 job centres in Northern Germany. Methods: The duration of the programme extended over a period of 10 weeks. All clients aged between 40 and 65 years were included. Phase 1consisted of a self-administered computer-based assessment, and if medical staff were present, blood pressure measurement and/or blood samples were taken. Participants without a history of cardiovascular diseases, interventional/surgical blood vessel procedures, diabetes and a body-mass-index ≤35 kg/m2 were invited to a specialised examination centre (phase 2). Logistic regression analysis was used to test predictors for participation in both phases. Variables were age, gender and for phase 2 the distance between participants' residence addresses and the address of the examination centre, cardiovascular risk factors, subjective health and socio-demographics. Results: 344 of the 1 049 invited job centre clients participated in the assessment. Women were more likely to participate than men. A number of 253 participants were invited for blood pressure measurement and blood sample taking. Participation of 209 persons was positively associated with age. A number of 138 participated in phase 2. Participation decreased with increasing distance between the participant's residence address and the address of the examination centre. Smokers, persons with less than 10 years of schooling and those who did not report an elevated level of blood lipids were less likely to participate. Conclusion: Blood pressure measurements and taking of blood samples in job centres were found to be highly accepted. The burden on potential participants to reach preventive measures should be minimised.

Association of Periodontal Destruction and Diabetes with Mortality.

Current evidence indicates the effects of periodontitis on diabetes as well as mortality, for which diabetes itself represents a risk factor. However, the possible interaction of these 2 chronic conditions regarding mortality has not yet been investigated. Therefore, the purpose of this study was to evaluate whether periodontal destruction interacts with diabetes on all-cause and cardiovascular disease (CVD) mortality or if diabetes serves as a mediator in this association. The study sample comprised 3,327 participants aged 20 to 81 y from the Study of Health in Pomerania. Periodontal destruction was assessed via clinical attachment level (CAL) and the number of missing teeth. Information on mortality (date and ICD-10 code) was ascertained from death certificates. Directed acyclic graphs were used to identify potential confounders, and Cox proportional hazard models were applied. In 36,701 person-years of follow-up, 263 study participants deceased, 89 due to CVD. Fully adjusted main effect models resulted in hazard ratios of 1.01 (95% confidence interval [95% CI]: 1.002 to 1.01) for extent of CAL ≥3 mm, 1.10 (95% CI: 1.03 to 1.18) for mean CAL, and 1.03 (95% CI: 1.01 to 1.04) for the number of missing teeth regarding all-cause mortality. Analogous results were obtained for CVD mortality, with hazard ratios of 1.01 (95% CI: 0.99 to 1.02), 1.10 (95% CI: 0.98 to 1.23), and 1.02 (95% CI: 0.99 to 1.05) for extent of CAL, mean CAL, and the number of missing teeth, respectively. Findings did not indicate additive interaction of periodontal destruction and diabetes regarding all-cause and CVD mortality. Similarly, no substantial evidence was found to demonstrate the presence of multiplicative interaction or mediation. Besides adjustment for baseline covariates, time-varying covariates were also considered and led to comparable results. In summary, despite their reciprocal relationship, periodontal destruction and diabetes may be independent risk factors for all-cause and CVD mortality.

Reduced Bone Stiffness in Women Is Associated with Clinical Attachment and Tooth Loss: The Study of Health in Pomerania.

The authors evaluated the association of reduced bone stiffness of the calcaneus with clinical attachment loss (CAL) and tooth loss. The authors analyzed data from 4,678 subjects (2,384 women), aged 20 to 88 y, from the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) and the baseline examination of the SHIP-Trend cohort. Bone stiffness, characterized by the stiffness index (SI) and the osteoporotic fracture risk (OFR), was assessed by quantitative ultrasound of the heel. SI and OFR were significantly associated with the mean CAL in women. While 1) the SI showed a significant association with the mean CAL and 2) the OFR with the median number of teeth in just the postmenopausal women, the OFR showed a significant association with mean CAL for both pre- and postmenopausal women. In postmenopausal women, a 10-unit increase in the SI was associated with a decrease in the mean CAL of 0.05 mm (95% confidence interval [CI]: -0.10 to 0.00; P = 0.046). Moreover, the adjusted median number of teeth was 21.4 (95% CI: 20.9 to 21.9) among the postmenopausal women with a low OFR, while it was 19.1 (95% CI: 17.8 to 20.3; P = 0.001) among the postmenopausal women with a high OFR. For the premenopausal women with a low OFR, the mean CAL was 1.60 mm (95% CI: 1.53 to 1.66), while for the premenopausal women with a high OFR, it was 2.24 mm (95% CI: 1.78 to 2.69; P = 0.006). Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men.

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

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 3.1 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 26.6 to 13.0 Gy × cm(2)), number of radiographic frames (-29%) and runs (-8%), radiographic DAP/frame (-2%), fluoroscopic DAP/s (-39%), and fluoroscopy time (-16%). Multilevel analysis revealed lower DAPs with decreasing body mass index (-1.4 Gy × cm(2) per kg/m(2)), age (-1.2 Gy × cm(2)/decade), female sex (-5.9 Gy × cm(2)), participation of the team leader (-9.4 Gy × cm(2)), the mini-course itself (-16.1 Gy × cm(2)), experience (-0.7 Gy × cm(2)/1000 CAs throughout the interventionalist's professional life), and use of older catheterization systems (-6.6 Gy × cm(2)). 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.

[Exercise training as a key component of heart failure therapy]. / Körperliches Training als wichtige Komponente der Therapie bei Herzinsuffizienz.

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.

Introducing a new method to assess vision: Computer-adaptive contrast-sensitivity testing predicts visual functioning better than charts in multiple sclerosis patients.

BACKGROUND: Impaired low-contrast visual acuity (LCVA) is common in multiple sclerosis (MS) and other neurological diseases. Its assessment is often limited to selected contrasts, for example, 2.5% or 1.25%. Computerized adaptive testing with the quick contrast-sensitivity function (qCSF) method allows assessment across expanded contrast and spatial frequency ranges. OBJECTIVE: The objective of this article is to compare qCSF with high- and low-contrast charts and patient-reported visual function. METHODS: We enrolled 131 consecutive MS patients (mean age 39.6 years) to assess high-contrast visual acuity (HCVA) at 30 cm and 5 m, low-contrast vision with Sloan charts at 2.5% and 1.25%, qCSF and the National Eye Institute Visual Functioning Questionnaire (NEIVFQ). Associations between the different measures were estimated with linear regression models corrected for age, gender and multiple testing. RESULTS: The association between qCSF and Sloan charts (R2 = 0.68) was higher than with HCVA (5 m: R2 = 0.5; 30 cm: R2 = 0.41). The highest association with NEIVFQ subscales was observed for qCSF (R2 0.20-0.57), while Sloan charts were not associated with any NEIVFQ subscale after correction for multiple testing. CONCLUSION: The qCSF is a promising new outcome for low-contrast vision in MS and other neurological diseases. Here we show a closer link to patient-reported visual function than standard low- and high-contrast charts.

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

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

ECG-gated coronary angiography enables submillisievert imaging in invasive cardiology.

BACKGROUND: The median dose area products (DAP) and effective doses (ED) of patients arising from coronary angiography (CA) are considerable: According the 2013 National German Registry, they amount to 19.8 Gy × cm(2) and 4.0 mSv, respectively. METHODS: We investigated the feasibility of prospective electrocardiogram (ECG)-gated coronary angiography (CA)-a novel technique in invasive cardiology-with respect to possible reduction in irradiation effects. Instead of universally fix-rated radiographic acquisition within 7.5-15 frames/s, one single frame/heartbeat was triggered toward the diastolic moment immediately before atrial contraction (77 % of ECG-RR interval) most likely to provide motion-free and hence optimized resolution of the coronary tree. For 200 patients (body mass index 27.8 kg/m(2), age 67.5 years, male 55 %, 68 bpm) undergoing ECG-gated CA, we measured various median (interquartile range) parameters for radiation exposure. RESULTS: The total DAP was 0.64 (0.46-1.00), radiographic fraction was 0.30 (0.19-0.43), and fluoroscopic fraction was 0.35 (0.21-0.57) Gy × cm(2). Radiographic imaging occurred within 21.7 s (17.1-26.3), with 25 frames (20-30) over the course of 7 runs (6-8). Fluoroscopy time was 119 s (94-141). Radiographic DAP was 12.6 mGy × cm(2)/frame and 13.8 mGy × cm(2)/s. Fluoroscopic DAP was 0.8 mGy × cm(2)/pulse and 3.1 mGy × cm(2)/s. Patient reference point air kerma was 17.0 mGy (11.1-28.1) and contrast volume was 70 ml (60-85). CONCLUSION: In conclusion, invasive ECG-gated coronary imaging is feasible in clinical routine and enables patient EDs of approx. 3 % of typical values in invasive cardiology: 0.13 mSv (0.09-0.20).

Latest-generation catheterization systems enable invasive submillisievert coronary angiography.

BACKGROUND: The radiation risk of patients undergoing invasive cardiology remains considerable and includes skin injuries and cancer. To date, submillisievert coronary angiography has not been considered feasible. PATIENTS AND METHODS: In 2011, we compared results from 100 consecutive patients undergoing elective coronary angiography using the latest-generation flat-panel angiography system (FPS) with results from examinations by the same operator using 106 historic controls with a conventional image-intensifier system (IIS) that was new in 2002. RESULTS: The median patient exposure parameters were measured as follows: dose-area product (DAP) associated with radiographic cine acquisitions (DAP(R)) and fluoroscopy (DAP(F)) scenes, radiographic frames and runs, and cumulative exposure times for radiography and fluoroscopy. On the FPS as compared to the traditional IIS, radiographic detector entrance dose levels were reduced from 164 to 80 nGy/frame and pulse rates were lowered from 12.5/s to 7.5/s during radiography and from 25/s to 4/s during fluoroscopy. The cardiologist's performance patterns remained comparable over the years: fluoroscopy time was constant and radiography time even slightly increased. Overall patient DAP decreased from 7.0 to 2.4 Gy × cm(2); DAP(R), from 4.2 to 1.7 Gy × cm(2); and DAP(F), from 2.8 to 0.6 Gy × cm(2). Time-adjusted DAP(R)/s decreased from 436 to 130 mGy × cm(2) and DAP(F)/s, from 21.6 to 4.4 mGy × cm(2). Cumulative patient skin dose with the FPS amounted to 67 mGy, and the median (interquartile range) of effective dose was 0.5 (0.3 … 0.7) mSv. CONCLUSION: Consistent application of radiation-reducing techniques with the latest-generation flat-panel systems enables submillisievert coronary angiography in invasive cardiology.