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Abstract The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p

Background: Although pulmonary embolism (PE) and sarcopenia are common diseases, only a few studies have assessed the impact of sarcopenia in PE on usage of reperfusion treatments in PE. Methods: All hospitalizations of PE patients aged ≥75 years 2005–2020 in Germany were included in this study and stratified for sarcopenia. Impact of sarcopenia on treatment procedures and adverse in-hospital events were investigated. Results: Overall, 576,364 hospitalizations of PE patients aged ≥75 years (median age 81.0 [78.0–85.0] years; 63.3 % females) were diagnosed in Germany during the observational period 2005–2020. Among these, 2357 (0.4 %) were coded with sarcopenia. PE patients with sarcopenia were in median 2 years older (83.0 [79.0–87.0] vs. 81.0 [78.0–85.0] years, P

Introduction: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world’s population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons. Aim and Methods: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink®) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated. Results: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed. Conclusion: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.

Transportation noise is a ubiquitous urban exposure. In 2018, the World Health Organization concluded that chronic exposure to road traffic noise is a risk factor for ischemic heart disease. In contrast, they concluded that the quality of evidence for a link to other diseases was very low to moderate. Since then, several studies on the impact of noise on various diseases have been published. Also, studies investigating the mechanistic pathways underlying noise-induced health effects are emerging. We review the current evidence regarding effects of noise on health and the related disease-mechanisms. Several high-quality cohort studies consistently found road traffic noise to be associated with a higher risk of ischemic heart disease, heart failure, diabetes, and all-cause mortality. Furthermore, recent studies have indicated that road traffic and railway noise may increase the risk of diseases not commonly investigated in an environmental noise context, including breast cancer, dementia, and tinnitus. The harmful effects of noise are related to activation of a physiological stress response and nighttime sleep disturbance. Oxidative stress and inflammation downstream of stress hormone signaling and dysregulated circadian rhythms are identified as major disease-relevant pathomechanistic drivers. We discuss the role of reactive oxygen species and present results from antioxidant interventions. Lastly, we provide an overview of oxidative stress markers and adverse redox processes reported for noise-exposed animals and humans. This position paper summarizes all available epidemiological, clinical, and preclinical evidence of transportation noise as an important environmental risk factor for public health and discusses its implications on the population level.

Abstract Vaccination rates are still insufficient to prevent the spread of COVID-19, so immunity must be increased among the population in order to reduce the virus’ spread and the associated medical and psychosocial effects. Although previous work has identified various factors associated with a low willingness to get vaccinated, the role of emotions such as fear of vaccination (FVAC) or fear of COVID-19 (FCOV), vaccination as a subjective norm (SN), psychological factors like general control beliefs (CB) or psychological resilience, and their interaction have been investigated less intensively. We used data from three cross-sectional waves of the German Panel COSMO (November 2021, N = 1010; February 2022, N = 1026; March 2022, N = 1031) and multiple logistic regression analyses to test whether vaccination rates are moderated by those factors. After controlling for covariates (age, sex, confidence in own intuition, optimism, well-being), we found that CB was no significant predictor of vaccination status. Higher FCOV and higher ratings in SN, however, were associated with an increased likelihood of being vaccinated. In contrast, higher FVAC was associated with a decreased likelihood of being vaccinated. Psychological resilience did not consistently moderate the associations between fear and vaccination status.

BackgroundTranscatheter aortic valve implantation (TAVI) is a standard treatment for patients with aortic valve stenosis due to its very low mortality and complication rates. However, survival and physical integrity are not the only important factors. Quality of life (QoL) improvement is a crucial part in the evaluation of therapy success.MethodsPatients with TAVI were questioned about their QoL before, one month and one year after the intervention as part of the INTERVENT registry trial at Mainz University Medical Center. Three different questionnaires were included in the data collection (Katz ADL, EQ-5D-5l, PHQ-D).ResultsWe included 285 TAVI patients in the analysis (mean age 79.8 years, 59.4% male, mean EuroSCORE II 3.8%). 30-day mortality was 3.6%, complications of any kind occurred in 18.9% of the patients. Main finding was a significant increase in the general state of health measured on the visual analog scale by an average of 4.53 (± 23.58) points (BL to 1-month follow-up, p = 0.009) and by 5.19 (± 23.64) points (BL to 12-month follow-up, p = 0.016). There was also an improvement of depression symptoms, which was reflected in a decrease in the total value of the PHQ-D by 1.67 (± 4.75) points (BL to 12-month follow-up, p = 0.001). The evaluation of the EQ-5D-5l showed a significant improvement in mobility after one month (M = −0.41 (± 1.31), p

Neurodegenerative diseases are often referred to as diseases of old age, and with the aging population, they are gaining scientific and medical interest. Environmental stressors, most notably traffic noise and air pollution, have recently come to the forefront, and have emerged as disease risk factors. The evidence for a connection between environmental risk factors and neurodegenerative disease is growing. In this review, the most common neurodegenerative diseases and their epidemiological association with traffic noise and air pollution are presented. Also, the most important mechanisms involved in neurodegenerative disease development, oxidative stress, and neuroinflammation are highlighted. An overview of the in vivo findings will provide a mechanistic link between noise, air pollution, and neurodegenerative pathology. Finally, the importance of the direct and indirect pathways, by which noise and air pollution cause cerebral damage, is discussed. More high-quality data are still needed from both epidemiological and basic science studies in order to better understand the causal connection between neurodegenerative diseases and environmental risk factors.

During the last two decades, large epidemiological studies have shown that the physical environment, including noise, air pollution or heavy metals, have a considerable impact on human health. It is known that the most common cardiovascular risk factors are all associated with endothelial dysfunction. Vascular tone, circulation of blood cells, inflammation, and platelet activity are some of the most essential functions regulated by the endothelium that suffer negative effects as a consequence of environmental pollution, causing endothelial dysfunction. In this review, we delineate the impact of environmental risk factors in connection to endothelial function. On a mechanistic level, a significant number of studies suggest the involvement of endothelial dysfunction to fundamentally drive the adverse endothelium health effects of the different pollutants. We focus on well-established studies that demonstrate the negative effects on the endothelium, with a focus on air, noise, and heavy metal pollution. This in-depth review on endothelial dysfunction as a consequence of the physical environment aims to contribute to the associated research needs by evaluating current findings from human and animal studies. From a public health perspective, these findings may also help to reinforce efforts promoting the research for adequate promising biomarkers for cardiovascular diseases since endothelial function is considered a hallmark of environmental stressor health effects.

Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM the lungs. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.

The results from epidemiological studies suggest that environmental noise including aircraft, railway, road traffic, wind turbine, and leisure-related noise is a growing public health concern. According to the WHO, at least 100 million people in the European Union are affected by traffic noise levels above the WHO-recommended thresholds. Environmental noise can adversely affect physical and mental health, as well as wellbeing. Chronic low-level noise exposure typical for most environmental sources is associated with psychophysiological stress causing non-auditory or indirect noise effects leading ultimately to cardiovascular diseases. Among all environmental noise sources, aircraft noise is considered the most annoying, and its leading mechanism of action is autonomic system activation such as increases in heart rate and blood pressure. Previously, we observed that long-term exposure to aircraft noise was associated with increased diastolic blood pressure, arterial stiffness (as assessed by pulse wave velocity), and impaired left ventricular diastolic function. All mentioned above effects are early, subclinical, and potentially reversible changes which preceded late noise effects in the cardiovascular system, that is, established cardiovascular diseases such as myocardial infarction, stroke, and heart failure. However, even a short-term reduction in aircraft noise exposure as observed during the COVID-19 lockdown may reverse these negative effects on arterial stiffness and blood pressure and may decrease the prevalence of insomnia. In this review, we aimed to critically discuss our obtained results considering recent studies on the influence of aircraft noise (and other traffic noises) on cardiovascular diseases in the context of the WHO Environmental Noise Guidelines for the European Region.

BackgroundWhile chronic exposure to high levels of noise was demonstrated to increase the risk of various cardiovascular diseases, the association between noise annoyance and risk of cardiovascular disease remains still inconsistent. Recently, we showed that noise annoyance is associated with prevalent atrial fibrillation in the general population. However, the association between noise annoyance and risk of incident atrial fibrillation as well as potential sex-differences remain still elusive.Methods and results15,010 subjects from a German population-based cohort were examined at baseline (2007 to 2012) and follow-up five years later (2012 to 2017) to investigative the association between noise annoyance due to multiple sources and prevalent and incident atrial fibrillation. After multivariable adjustment, the results from logistic regression analyses revealed overall consistent and positive associations between noise annoyance and prevalent and incident atrial fibrillation in men, whereas this association was weaker in women, in particular with respect to incident atrial fibrillation. For instance, industrial noise annoyance was associated with 21% (95% confidence interval (CI) 9–34%) and 18% (8–29%) higher odds of prevalent atrial fibrillation in men and women, respectively. In prospective analysis, this association remained stable in men (odds ratio (OR) 1.25, 1.07–1.44), while in women no association was observed (OR 1.03, 0.89–1.18).ConclusionsThe findings suggest that noise annoyance can increase the risk of incident atrial fibrillation in a large population-based cohort and that men may be more sensitive to the adverse effects of noise annoyance with regard to the risk of atrial fibrillation.

Abstract Echocardiography is the most common routine cardiac imaging method. Nevertheless, only few data about sex-specific reference limits for right atrium (RA) dimensions are available. Transthoracic echocardiographic RA measurements were studied in 9511 participants of the Gutenberg-Health-Study. A reference sample of 1942 cardiovascular healthy subjects without chronic obstructive pulmonary disease was defined. We assessed RA dimensions and sex-specific reference limits were defined using the 95th percentile of the reference sample. Results showed sex-specific differences with larger RA dimensions in men that were attenuated by standardization for body-height. RA-volume was 20.2 ml/m in women (5th–95th: 12.7–30.4 ml/m) and 26.1 ml/m in men (5th–95th: 16.0–40.5 ml/m). Multivariable regressions identified body-mass-index (BMI), coronary artery disease (CAD), chronic heart failure (CHF) and atrial fibrillation (AF) as independent key correlates of RA-volume in both sexes. All-cause mortality after median follow-up-period of 10.7 (9.81/11.6) years was higher in individuals who had RA volume/height outside the 95% reference limit (HR 1.70 [95%CI 1.29–2.23], P = 0.00014)). Based on a large community-based sample, we present sex-specific reference-values for RA dimensions normalized for height. RA-volume varies with BMI, CHF, CAD and AF in both sexes. Individuals with RA-volume outside the reference limit had a 1.7-fold higher mortality than those within reference limits.

Abstract Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35–74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β − 0.36, 95% CI − 0.63/− 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β − 0.34, 95% CI − 0.53/− 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β − 0.656, 95% CI − 1.07/− 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HRperSD) 1.60, 95% CI 1.39–1.85; P

Background: Diabetes mellitus (DM) represents a relevant risk factor regarding morbidity and mortality worldwide. However, only limited data exist regarding the impact of DM on the clinical outcome of patients with COVID-19 infection. Methods: All hospitalized patients with confirmed COVID-19-infection (ICD-code U07.1) during the year 2020 in Germany were included in the present study. Patients were stratified regarding the co-prevalence of DM (ICD-codes E10-E14), and the impact of DM on in-hospital case fatality and in-hospital adverse events was analyzed. Results: Overall, 176,137 hospitalizations with confirmed COVID-19 infection were documented; of these, 45,232 (25.7%) patients had an additional diagnosis of DM. Diabetic patients with COVID-19 were more often of male sex and 7 years older (median 76.0 (IQR: 66.0–83.0) vs. 69.0 (52.0–81.0) years, p < 0.001). COVID-19 patients with DM demonstrated an aggravated comorbidity profile, as reflected by a higher Charlson comorbidity index (6.0 (IQR: 4.0–8.0) vs. 3.0 (1.0–5.0), p < 0.001). Risk for pneumonia (OR 1.38 (95% CI: 1.35–1.41), p < 0.001), acute respiratory distress syndrome (OR 1.53 (95% CI: 1.47–1.60), p < 0.001), and need for intensive care (21.3% vs. 13.3%, p < 0.001) were increased in DM patients. DM was an independent risk factor for acute kidney failure (OR 1.49 (95% CI: 1.44–1.53), p < 0.001), dialysis (OR 1.56 (95% CI: 1.47–1.66), p < 0.001), mechanical ventilation (OR: 1.49 (95% CI: 1.43–1.56), p < 0.001), extracorporeal membrane oxygenation (OR 1.44 (95% CI: 1.27–1.62), p < 0.001), major adverse cardiac and cerebrovascular events (OR: 1.24 (95% CI: 1.20–1.27), p < 0.001), and in-hospital mortality (OR: 1.26 (95% CI: 1.22–1.30), p < 0.001). Conclusions: In patients with COVID-19-infection, DM is a relevant risk factor for adverse events, including mortality. The vulnerable patient group of diabetics with COVID-19 requires intense medical care and monitoring during hospitalization.

The importance of noise exposure as a major environmental determinant of public health is being increasingly recognized. While in recent years a large body evidence has emerged linking environmental noise exposure mainly to cardiovascular disease, much less is known concerning the adverse health effects of noise on the brain and associated neuropsychiatric outcomes. Despite being a relatively new area of investigation, indeed, mounting research and conclusive evidence demonstrate that exposure to noise, primarily from traffic sources, may affect the central nervous system and brain, thereby contributing to an increased risk of neuropsychiatric disorders such as stroke, dementia and cognitive decline, neurodevelopmental disorders, depression, and anxiety disorder. On a mechanistic level, a significant number of studies suggest the involvement of reactive oxygen species/oxidative stress and inflammatory pathways, among others, to fundamentally drive the adverse brain health effects of noise exposure. This in-depth review on the cerebral consequences of environmental noise exposure aims to contribute to the associated research needs by evaluating current findings from human and animal studies. From a public health perspective, these findings may also help to reinforce efforts promoting adequate mitigation strategies and preventive measures to lower the societal consequences of unhealthy environments.

Cultural and biographical influences on the expression of emotions manifest themselves in so-called “display rules.” These rules determine the time, intensity, and situations in which an emotion is expressed. To date, only a small number of empirical studies deal with this transformation of how migrants, who are faced with a new culture, may change their emotional expression. The present, cross-sectional study focuses on changes in anger expression as part of a complex acculturation process among Iranian migrants. To this end, Iranian citizens in Iran (n = 61), German citizens (n = 61), and Iranian migrants in Germany (n = 60) were compared in terms of anger expression behavior and acculturation strategy (assimilation, separation, integration, marginalization) was assessed among the migrants, using the Frankfurt Acculturation Scale (FRACC). A questionnaire developed in a preliminary study was used to measure anger expression via subjective anger experience and anger expression within 16 hypothetical situations. Multivariate Analyses of Variance (MANOVA) revealed that Iranians and Iranian migrants reported higher anger experience ratings than Germans and directed their anger more often inward (anger-in). Further findings suggest that transformation processes may have affected Iranian migrants in terms of suppressed anger (anger-in): Iranian migrants with a higher orientation toward German culture reported lower average anger-in scores. These results suggest that there was different emotional expression among Iranian migrants, depending on their acculturation. The results provide new insight into socio-cultural and individual adjustment processes.

Abstract Aims Mitral annuloplasty using the Carillon Mitral Contour System (CMCS) reduces secondary mitral regurgitation (SMR) and leads to reverse left ventricular remodelling. The aim of this study was to evaluate the effect of the CMCS on the mitral valve annulus (MA) and left atrial volume (LAV). Methods and results We retrospectively evaluated the data of all patients treated with the CMCS at our centre. Using transthoracic echocardiography, MA diameters were assessed by measuring the anterolateral to posteromedial extend (ALPM) and the anterior to posterior (AP) dimensions, respectively. Also, LAV and left ventricular end‐diastolic volume (LVEDV) were assessed. Patients were examined at three time points: baseline, at 20–60 days (30dFUP), and at 9–15 months (1yFUP), using paired analysis. From July 2014 until March 2019, 75 cases of severe SMR were treated using CMCS. Cases in which other devices were used in combination (COMBO therapy, n = 35) or in which the device could not be implanted (implant failure, n = 3) were excluded, leaving 37 patients in the present analysis. Analysis at 30dFUP showed a significant reduction of 16% in the mean ALPM diameter (7.27 ± 5.40 mm) and 15% in the AP diameter (6.57 ± 5.33 mm). Analysis of LAV also showed a significant reduction of 21% (36.61 ± 82.67 mL), with no significant change in LVEDV. At 1yFUP, the reduction of both the mean ALPM diameter of 14% (6.24 ± 5.70 mm) and the mean AP diameter of 12% (5.46 ± 4.99 mm) remained significant and stable. The reduction in LAV was also maintained at 23% (37.03 ± 56.91 mL). LAV index was significantly reduced by 17% at 30dFUP (15.44 ± 40.98 mL/m2) and by 13% at 1yFUP (11.56 ± 31.87 mL/m2), respectively. LVEDV index showed no significant change at 30dFUP and a non‐significant 10% reduction at 1yFUP (17.75 ± 58.79 mL/m2). Conclusions The CMCS successfully treats symptomatic SMR with a stable reduction of not only the AP diameter of the MA, but the current study also demonstrates an additional reduction of the ALPM dimension at both 30dFUP and 1yFUP. We have also shown for the first time that LAV and LAV index are significantly reduced at both 30dFUP and 1yFUP and a non‐significant positive remodelling of the LVEDV. This positive left atrial remodelling has not been looked for and demonstrated in earlier randomized studies of CMCS.

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure. C57BL/6J mice were exposed to aircraft noise for 0, 4, 7, 14 and 28d at a mean sound pressure level of 72 dB(A) and peak levels of 85 dB(A). Chronic aircraft noise exposure up to 28d caused persistent endothelial dysfunction and elevation of blood pressure. Likewise, reactive oxygen species (ROS) formation as determined by dihydroethidium (DHE) staining and HPLC-based measurement of superoxide formation in the aorta/heart/brain was time-dependently increased by noise. Oxidative burst in the whole blood showed a maximum at 4d or 7d of noise exposure. Increased superoxide formation in the brain was mirrored by a downregulation of neuronal nitric oxide synthase (Nos3) and transcription factor Foxo3 genes, whereas Vcam1 mRNA, a marker for inflammation was upregulated in all noise exposure groups. Induction of a pronounced hearing loss in the mice was excluded by auditory brainstem response audiometry. Endothelial dysfunction and inflammation were present during the entire 28d of aircraft noise exposure. ROS formation gradually increases with ongoing exposure without significant adaptation or tolerance in mice in response to chronic noise stress at moderate levels. These data further illustrate health side effects of long-term noise exposure and further strengthen a consequent implementation of the WHO noise guidelines in order to prevent the development of noise-related future cardiovascular disease.

Environmental exposures represent a significant health hazard, which cumulatively may be responsible for up to 2/3 of all chronic non-communicable disease and associated mortality (Global Burden of Disease Study and The Lancet Commission on Pollution and Health), which has given rise to a new concept of the exposome: the sum of environmental factors in every individual’s experience. Noise is part of the exposome and is increasingly being investigated as a health risk factor impacting neurological, cardiometabolic, endocrine, and immune health. Beyond the well-characterized effects of high-intensity noise on cochlear damage, noise is relatively well-studied in the cardiovascular field, where evidence is emerging from both human and translational experiments that noise from traffic-related sources could represent a risk factor for hypertension, ischemic heart disease, diabetes, and atherosclerosis. In the present review, we comprehensively discuss the current state of knowledge in the field of noise research. We give a brief survey of the literature documenting experiments in noise exposure in both humans and animals with a focus on cardiovascular disease. We also discuss the mechanisms that have been uncovered in recent years that describe how exposure to noise affects physiological homeostasis, leading to aberrant redox signaling resulting in metabolic and immune consequences, both of which have considerable impact on cardiovascular health. Additionally, we discuss the molecular pathways of redox involvement in the stress responses to noise and how they manifest in disruptions of the circadian rhythm, inflammatory signaling, gut microbiome composition, epigenetic landscape and vessel function.

Epidemiological studies showed that traffic noise has a dose-dependent association with increased cardiovascular morbidity and mortality. Whether microvascular dysfunction contributes significantly to the cardiovascular health effects by noise exposure remains to be established. The connection of inflammation and immune cell interaction with microvascular damage and functional impairment is also not well characterized. Male C57BL/6J mice or gp91phox−/y mice with genetic deletion of the phagocytic NADPH oxidase catalytic subunit (gp91phox or NOX-2) were used at the age of 8 weeks, randomly instrumented with dorsal skinfold chambers and exposed or not exposed to aircraft noise for 4 days. Proteomic analysis (using mass spectrometry) revealed a pro-inflammatory phenotype induced by noise exposure that was less pronounced in noise-exposed gp91phox−/y mice. Using in vivo fluorescence microscopy, we found a higher number of adhesive leukocytes in noise-exposed wild type mice. Dorsal microvascular diameter (by trend), red blood cell velocity, and segmental blood flow were also decreased by noise exposure indicating microvascular constriction. All adverse effects on functional parameters were normalized or improved at least by trend in noise-exposed gp91phox−/y mice. Noise exposure also induced endothelial dysfunction in cerebral microvessels, which was associated with higher oxidative stress burden and inflammation, as measured using video microscopy. We here establish a link between a pro-inflammatory phenotype of plasma, activation of circulating leukocytes and microvascular dysfunction in mice exposed to aircraft noise. The phagocytic NADPH oxidase was identified as a central player in the underlying pathophysiological mechanisms.

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

Global epidemiological studies show that chronic non-communicable diseases such as atherosclerosis and metabolic disorders represent the leading cause of premature mortality and morbidity. Cardiovascular disease such as ischemic heart disease is a major contributor to the global burden of disease and the socioeconomic health costs. Clinical and epidemiological data show an association of typical oxidative stress markers such as lipid peroxidation products, 3-nitrotyrosine or oxidized DNA/RNA bases with all major cardiovascular diseases. This supports the concept that the formation of reactive oxygen and nitrogen species by various sources (NADPH oxidases, xanthine oxidase and mitochondrial respiratory chain) represents a hallmark of the leading cardiovascular comorbidities such as hyperlipidemia, hypertension and diabetes. These reactive oxygen and nitrogen species can lead to oxidative damage but also adverse redox signaling at the level of kinases, calcium handling, inflammation, epigenetic control, circadian clock and proteasomal system. The in vivo footprints of these adverse processes (redox biomarkers) are discussed in the present review with focus on their clinical relevance, whereas the details of their mechanisms of formation and technical aspects of their detection are only briefly mentioned. The major categories of redox biomarkers are summarized and explained on the basis of suitable examples. Also the potential prognostic value of redox biomarkers is critically discussed to understand what kind of information they can provide but also what they cannot achieve.

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction.Conclusions: Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.

This article contains supporting information on data collection for the research article entitled “Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice” by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of vascular reactivity in vitro. • visualization of noise-dependent effects in dorsal skinfold chamber. • in vivo microscopy of noise-dependent activation of white blood cells. • analysis of noise-dependent microvascular dysfunction in dorsal skinfold chamber and cannulated cerebral arterioles.

Introduction: Atherosclerosis and pulmonary embolism (PE) affect cardiovascular mortality substantially. We aimed to investigate the impact of atherosclerosis on the outcomes of patients with deep venous thrombosis (DVT) and to identify the differences in DVT patients with and without PE. Methods: Patients with DVT with and without symptomatic atherosclerosis (defined as coronary artery disease, myocardial infarction and/or peripheral artery disease) as well as with and without PE under oral anticoagulation were enrolled during January 2011–April 2013 and compared. The impact of symptomatic atherosclerosis on several outcomes was analyzed. Results: Overall, 509 DVT patients (70.0 [56.0–77.0] years, 51.9% females) were included in this study. Among them, 179 (36.3%) had symptomatic atherosclerosis and 204 (40.1%) a concomitant PE. DVT patients with symptomatic atherosclerosis were older (74.0 [IQR 65.0–80.0] vs. 63.0 [48.0–75.0] years, p < 0.0001), more often male (56.4% vs. 43.9%, p = 0.0087) and had a higher prevalence of classical CVRF and a higher Charlson comorbidity index (7.00 [5.00–8.00] vs. 4.00 [2.00–6.00], p < 0.001). Symptomatic atherosclerosis was associated with increased mortality (HR 1.98 [95%CI 1.12–3.49], p = 0.018) and hospitalizations (HR 1.64 [95%CI 1.21–2.21], p = 0.0012) and primary long-term outcome (HR 1.99 [95%CI 1.31–3.04], p = 0.0013) during the 2 years follow-up-period in DVT patients. DVT patients without PE had diabetes mellitus (28.2% vs. 16.3%, p < 0.01) and symptomatic atherosclerosis (42.9% vs. 26.4%, p < 0.001) more often compared to DVT patients with PE, and symptomatic atherosclerosis was associated with isolated DVT (without PE) (OR 2.01 [95%CI 1.28–3.16], p < 0.01). Conclusions: Atherosclerosis was associated with isolated DVT (without PE) and increased mortality in DVT patients under oral anticoagulation. The profile of CVRF and comorbidities differed between DVT patients with and without a concomitant PE. In the case of DVT or PE, patients should be screened for concomitant atherosclerotic disease. Clinical Trial Registration: at clinicaltrials with Unique identifier NCT01809015.

Arterial hypertension is the most important risk factor for the development of cardiovascular disease. Recently, aircraft noise has been shown to be associated with elevated blood pressure, endothelial dysfunction, and oxidative stress. Here, we investigated the potential exacerbated cardiovascular effects of aircraft noise in combination with experimental arterial hypertension. C57BL/6J mice were infused with 0.5 mg/kg/d of angiotensin II for 7 days, exposed to aircraft noise for 7 days at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A), or subjected to both stressors. Noise and angiotensin II increased blood pressure, endothelial dysfunction, oxidative stress and inflammation in aortic, cardiac and/or cerebral tissues in single exposure models. In mice subjected to both stressors, most of these risk factors showed potentiated adverse changes. We also found that mice exposed to both noise and ATII had increased phagocytic NADPH oxidase (NOX-2)-mediated superoxide formation, immune cell infiltration (monocytes, neutrophils and T cells) in the aortic wall, astrocyte activation in the brain, enhanced cytokine signaling, and subsequent vascular and cerebral oxidative stress. Exaggerated renal stress response was also observed. In summary, our results show an enhanced adverse cardiovascular effect between environmental noise exposure and arterial hypertension, which is mainly triggered by vascular inflammation and oxidative stress. Mechanistically, noise potentiates neuroinflammation and cerebral oxidative stress, which may be a potential link between both risk factors. The results indicate that a combination of classical (arterial hypertension) and novel (noise exposure) risk factors may be deleterious for cardiovascular health.

Environmental pollution and non-chemical stressors such as mental stress or traffic noise exposure are increasingly accepted as health risk factors with substantial contribution to chronic noncommunicable diseases (e.g. cardiovascular, metabolic and mental). Whereas the mechanisms of air pollution-mediated adverse health effects are well characterized, the mechanisms of traffic noise exposure are not completely understood, despite convincing clinical and epidemiological evidence for a significant contribution of environmental noise to overall mortality and disability. The initial mechanism of noise-induced cardiovascular, metabolic and mental disease is well defined by the „noise reaction model“ and consists of neuronal activation involving the hypothalamic-pituitary-adrenal (HPA) axis as well as the sympathetic nervous system, followed by a classical stress response via cortisol and catecholamines. Stress pathways are initiated by noise-induced annoyance and sleep deprivation/fragmentation. This review highlights the down-stream pathophysiology of noise-induced mental stress, which is based on an induction of inflammation and oxidative stress. We highlight the sources of reactive oxygen species (ROS) involved and the known targets for noise-induced oxidative damage. Part of the review emphasizes noise-triggered uncoupling/dysregulation of endothelial and neuronal nitric oxide synthase (eNOS and nNOS) and its central role for vascular dysfunction.

Both exposure to higher levels of polluted air and physical inactivity are crucial risk factors for the development and progression of major noncommunicable diseases and, in particular, of cardiovascular disease. In this context, the World Health Organization estimated 4.2 and 3.2 million global deaths per year in response to ambient air pollution and insufficient physical activity, respectively. While regular physical activity is well known to improve general health, it may also increase the uptake and deposit of air pollutants in the lungs/airways and circulation, due to increased breathing frequency and minute ventilation, thus increasing the risk of cardiovascular disease. Thus, determining the tradeoff between the health benefits of physical activity and the potential harmful effects of increased exposure to air pollution during physical activity has important public health consequences. In the present comprehensive review, we analyzed evidence from human and animal studies on the combined effects of physical activity and air pollution on cardiovascular and other health outcomes. We further report on pathophysiological mechanisms underlying air pollution exposure, as well as the protective effects of physical activity with a focus on oxidative stress and inflammation. Lastly, we provide mitigation strategies and practical recommendations for physical activity in areas with polluted air.

Despite extensive efforts to combat cigarette smoking/tobacco use, it still remains a leading cause of global morbidity and mortality, killing more than eight million people each year. While tobacco smoking is a major risk factor for non-communicable diseases related to the four main groups—cardiovascular disease, cancer, chronic lung disease, and diabetes—its impact on neuropsychiatric risk is rather elusive. The aim of this review article is to emphasize the importance of smoking as a potential risk factor for neuropsychiatric disease and to identify central pathophysiological mechanisms that may contribute to this relationship. There is strong evidence from epidemiological and experimental studies indicating that smoking may increase the risk of various neuropsychiatric diseases, such as dementia/cognitive decline, schizophrenia/psychosis, depression, anxiety disorder, and suicidal behavior induced by structural and functional alterations of the central nervous system, mainly centered on inflammatory and oxidative stress pathways. From a public health perspective, preventive measures and policies designed to counteract the global epidemic of smoking should necessarily include warnings and actions that address the risk of neuropsychiatric disease.

Background Endothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development. Methods and Results In a population‐based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35–74 years at enrollment in 2007–2012), we identified 1610 cases of incident pre–diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A1c (HbA1c) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow‐mediated dilation and digital volume plethysmography–derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate β coefficients of HbA1c levels at follow‐up and relative risks of incident (pre–)diabetes mellitus. Reactive hyperemia index was independently associated with HbA1c after multivariable adjustment for baseline HbA1c, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack‐years of smoking, non–high‐density lipoprotein/high‐density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C‐reactive protein (β=−0.020; P=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02–1.15; P=0.012) for incident pre–diabetes mellitus and 1.16 (95% CI, 1.01–1.34; P=0.041) for incident type 2 diabetes mellitus. Flow‐mediated dilation independently increased the relative risk for developing pre–diabetes mellitus by 8% (95% CI, 1.02–1.14; P=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86–1.19; P=0.92) and with HbA1c (β=−0.003; P=0.59). Conclusions Endothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre–)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.

The World Health Organization estimates that only approximately 25% of diversity in longevity is explained by genetic factors, while the other 75% is largely determined by interactions with the physical and social environments. Indeed, aging is a multifactorial process that is influenced by a range of environmental, sociodemographic, and biopsychosocial factors, all of which might act in concert to determine the process of aging. The global average life expectancy increased fundamentally over the past century, toward an aging population, correlating with the development and onset of age-related diseases, mainly from cardiovascular and neurological nature. Therefore, the identification of determinants of healthy and unhealthy aging is a major goal to lower the burden and socioeconomic costs of age-related diseases. The role of environmental factors (such as air pollution and noise exposure) as crucial determinants of the aging process are being increasingly recognized. Here, we critically review recent findings concerning the pathomechanisms underlying the aging process and their correlates in cardiovascular and neurological disease, centered on oxidative stress and inflammation, as well as the influence of prominent environmental pollutants, namely air pollution and traffic noise exposure, which is suggested to accelerate the aging process. Insight into these types of relationships and appropriate preventive strategies are urgently needed to promote healthy aging.

Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson’s disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.