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Abstract Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p

Abstract Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC–MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of “frailty” and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrated strong beneficial effects of repetitive activities, such as active commuting or leisure‐time PA–related walking on AS in men, but not in women. Lower AS associated with endurance training was also found among men and premenopausal women. In contrast, intense occupational PA was related to stiffer vessels in men (P

Abstract Background Increasing survival rates after childhood cancer have raised the issue of long‐term mental health consequences in adulthood. This study determines mental health distress among long‐term survivors of pediatric cancer and compares it to control groups. Methods Childhood cancer survivors (CCS; N = 951, aged 24‐49 years) were compared to three age‐matched control groups from the general population collected at three time points. The study compared the prevalence of clinically relevant symptoms of a wide range of common mental disorders (depression, somatic distress, suicidal ideation, generalized anxiety, panic, social anxiety, and sleep disturbances) using identical, validated questionnaires. CCS were identified by the German Childhood Cancer Registry. Controls were approached by a demographic consultation company (USUMA) which assured that the three samples were nationally representative. Results Childhood cancer survivors reported higher education than controls and were less often married. All forms of common mental distress were increased among survivors. Twenty‐four percent of male (N = 526) and 41% of female survivors (N = 425) reported some form of clinically relevant mental health symptoms. Somatic distress as the leading complaint was highly frequent among CCS (OR: 10.98, CI 95%: 7.24‐16.64). Complaints by generalized anxiety (OR: 5.04, CI 95%: 2.61‐9.70), panic (OR: 3.28, CI 95%: 1.60‐6.70), depression (OR: 3.36, CI 95%: 2.22‐5.09), and suicidality (OR = 2.22; CI 95%: 1.38‐3.57) were also strongly increased. Female sex, low education, low income, and unemployment were associated with increased distress. Conclusions Findings indicate a need to integrate psycho‐oncological screening and care into long‐term aftercare. Somatic distress, as cause and indicator of psychological distress, should receive stronger attention, especially tiredness, low energy, and pain.

BackgroundAn inducible release of soluble junctional adhesion molecule-A (sJAM-A) under pro-inflammatory conditions was described in cultured non-CNS endothelial cells (EC) and increased sJAM-A serum levels were found to indicate inflammation in non-CNS vascular beds. Here we studied the regulation of JAM-A expression in cultured brain EC and evaluated sJAM-A as a serum biomarker of blood-brain barrier (BBB) function.Methodology/principal findingsAs previously reported in non-CNS EC types, pro-inflammatory stimulation of primary or immortalized (hCMEC/D3) human brain microvascular EC (HBMEC) induced a redistribution of cell-bound JAM-A on the cell surface away from tight junctions, along with a dissociation from the cytoskeleton. This was paralleled by reduced immunocytochemical staining of occludin and zonula occludens-1 as well as by increased paracellular permeability for dextran 3000. Both a self-developed ELISA test and Western blot analysis detected a constitutive sJAM-A release by HBMEC into culture supernatants, which importantly was unaffected by pro-inflammatory or hypoxia/reoxygenation challenge. Accordingly, serum levels of sJAM-A were unaltered in 14 patients with clinically active multiple sclerosis compared to 45 stable patients and remained unchanged in 13 patients with acute ischemic non-small vessel stroke over time.ConclusionSoluble JAM-A was not suited as a biomarker of BBB breakdown in our hands. The unexpected non-inducibility of sJAM-A release at the human BBB might contribute to a particular resistance of brain EC to inflammatory stimuli, protecting the CNS compartment.