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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., Graphical abstract Image 1, Highlights • Global burden of disease, oxidative stress and cardiovascular disease (CVD). • Discussion of the different categories of redox biomarkers in CVD. • Discussion of prognostic value of classical oxidative stress markers in human CVD. • Discussion of novel redox biomarkers for risk stratification in human CVD. • Highlighting the additivity of redox biomarkers in human CVD comorbidities.

Background Transcatheter Aortic Valve Implantation (TAVI) is today the first option for older patients with aortic valve stenosis (AS) at intermediate or high risk for surgery. Constant development of bioprosthetic valves and delivery systems have reduced complications and improved outcomes over the years. The 3rd generation Edwards Sapien 3 Valve (S3) and the 2nd generation Medtronic Evolut R Valve (ER) are currently the most frequently used worldwide. There is a paucity of published data regarding long term outcomes in these new generation TAVI patients. Methods and results In our retrospective, single-center analysis we included patients with severe Aortic Stenosis who underwent transfemoral TAVI with a new generation prosthesis between 2014 and 2016. Peri- and postprocedural outcomes of these patients were analyzed according to the VARC-2 criteria. The study population consisted of 359 patients (mean patient age 82±7 years, 47% male, mean EuroSCORE II 8.0±8). The S3 group included 215 patients, the ER group 144 patients. Median follow-up period was 3.8 years (IQR 3.3 to 4.4 years, maximum follow-up in living patients 5.1 years). Device Success rates where equal in both groups (93.0% vs. 92.4%, p=0.812). We report a 30-day mortality of 2.8% in the S3 group, 2.1% in the ER group, respectively (p=0.674). There was no difference in stroke rate, conversion to open heart surgery, major vascular complications, life-threatening or disabling bleeding or myocardial infarction. Implantation of a new permanent pacemaker was lower in the S3 group (S3: 27.4% vs. ER: 44.5%, p=0.002). While prosthesis mean gradients where higher in the S3 group (12.0 mmHg vs. 8.2 mmHg, p All-Cause Mortality up to 5 years did not show a difference between both patient groups (mean survival S3 3.5 years, ER 3.3 years, p=0.895). Independent predictors of death where impaired left ventricular function (HR 1.61, p=0.007), chronic kidney injury (HR 1.55, p=0.032), peripheral artery disease (HR 2.10, p=0.003), malignant tumor (HR 2.40, p Discussion We present a comparison of the new-generation aortic valve prostheses Edwards Sapien 3 and Medtronic Evolut R concerning long-term as well as periprocedural outcomes. The analyzed cohort consisted of patients at intermediate to high surgical risk. Yet, 30-day mortality was very low both in S3 and ER patients. Device success and periprocedural outcomes in both groups were comparable and are in line with previous studies using VARC-2 definitions. Conclusion New generation TAVI valves offer an excellent implant and outcome success rate compared to early transcatheter Aortic valve replacement. Long-term survival was independent of prostheses choice and mainly attributed to pre- and intraprocedural comorbidities and complications. All-Cause Mortality (Kaplan-Meier) Funding Acknowledgement Type of funding source: None

Background Mitral valve regurgitation (MR) is a frequent heart valve disorder affecting 1–2% of the humans in the general population and over 10% of the individuals older than 75 years. While a symptomatic and prognostic benefit of transcatheter edge-to-edge repair for MR (TMVR) was reported, data regarding long-term outcome as well as influence of concomitant tricuspid regurgitation (TR) are sparse. Purpose We aimed to investigate the impact of periinterventional development of TR on survival of patients undergoing interventional edge-to-edge repair for MR in a large retrospective monocentric study. Methods We retrospectively analyzed survival of patients successfully treated with isolated edge-to-edge repair for MR from 06/2010–03/2018 (exclusion of combined forms of TMVR) in our center. Baseline, periprocedural as well as follow-up data were gathered. Concomitant TR was evaluated at baseline and after 30 days and categorized from grades 0 (no TR) to grade III (severe TR). We analyzed the influence of severe vs. non-severe TR on 30-day, 1-year and long-term survival. Results Overall, 627 consecutive patients (47.0% female, 57.4% functional MR) were enrolled. Median follow-up time was 462 days [IQR 142–945]. Survival status was available in 96.7%. Survival rates were 97.6% at discharge, 75.7% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7 years. TR at baseline (examination results were available in 92.3%) was categorized as severe TR in 25.6%, medium TR in 33.3%, mild TR in 35.1% and no TR in 6.0%. TR at 1 month (examination results were available in 81.1%) was severe in 16.7%, medium in 30.2%, mild in 45.6% and no TR was found in 7.4%; improvement by at least 1 TR-grade was documented in 33.6% of the patients. While a severe (compared to non-severe) TR at baseline did not affect the 30-day mortality (7.4% vs. 5.2%, p=0.354), 1-year survival was substantially impaired in those patients (36.5% vs. 23.0%, p=0.012). Accordingly, severe TR was not associated with 30d-mortality (as evaluated by univariate Cox regression, p=0.340), but with 1-year survival (HR 1.78, 95% CI 1.19–2.65, p=0.005) and showed a trend towards impaired long-term survival (HR 1.30, 95% CI 0.96–1.76, p=0.089). While residual severe TR at one month did not influence 1-year-mortality significantly (p=0.478), improvement of TR demonstrated a trend to better survival after the first year (86.9 vs. 81.0%, p=0.208) confirmed in the Cox regression analysis (HR 0.66, 95% CI 0.36–1.22, p=0.188). Conclusions In this large retrospective monocentric study with a long-term follow-up-period of >7 years after edge-to-edge therapy for MR, we demonstrated that severe TR at the time of the intervention had an impact on 1-year-survival. Furthermore, a missing periinterventional improvement of TR was shown to be unfavorable regarding the long-term survival of these patients. Funding Acknowledgement Type of funding source: None

E-cigarettes have become a controversial topic. While their benefits are questioned by the scientific community, a part of the medical profession is still supporting them as an effective harm reduction tool for smoking cessation. The impact of E-cigarettes on the cardiovascular system is still elusive.We assessed results from animal, pre(clinical), and epidemiological studies to critically evaluate and synthesize evidence relevant to the cardiovascular effects of E-cigarettes. Animal studies have demonstrated that E-cigarette vapor exposure can cause endothelial and cardiac dysfunction. However, there have also been reports on the less harmful effects of E-cigarette vapor exposure in comparison to classical tobacco cigarettes. Measurements of flow-mediated dilation in acute human exposure settings have mostly demonstrated that E-cigarettes cause vascular endothelial dysfunction. Epidemiological studies have shown that E-cigarette use is associated with an increased risk for cardiovascular disease, although switching from classical tobacco cigarettes to E-cigarettes can have beneficial cardiovascular effects. Misinterpretation of scientific data by activists on either side is another problem.In conclusion, we need more and better (pre)clinical data comparing the health effects of E-cigarette vaping as compared with tobacco cigarette smoking, in order to counsel the legislation for better health policies.

An increasing number of studies underlines the role of noise and air pollution as important environmental risk factors. It is unclear, how noise and air pollution impact mental health. Current study results indicate that environmental noise (in particular traffic noise) and various components of air pollution (in particular particulate matter) can increase the risk of mental disorders such as depression, anxiety disorders, psychoses and suicide. Pathophysiological mechanisms include both biological (such as oxidative stress and inflammation) and psychosocial factors (such as mental stress). Environmental risk factors such as noise and air pollution can have a significant impact on mental health. Due to the partly heterogeneous study results and the limited availability of methodically high-quality longitudinal studies, further studies are absolutely necessary, which allow deeper insights into these relationships.Immer mehr Studien unterstreichen die Rolle von Lärm und Luftverschmutzung als bedeutsame Umweltrisikofaktoren. Ungeklärt ist, welche Einflüsse Lärm und Luftverschmutzung auf die psychische Gesundheit ausüben. Aktuelle Studienergebnisse zeigen, dass Umgebungslärm (vor allem Verkehrslärm) und verschiedene Bestandteile von Luftverschmutzung (vor allem Feinstaub) das Risiko für psychische Erkrankungen wie Depressionen, Angststörungen, Psychosen und Suizid erhöhen können. Pathophysiologische Mechanismen umfassen sowohl biologische (wie oxidativen Stress und Inflammation) als auch psychosoziale Faktoren (wie mentalen Stress). Umweltrisikofaktoren wie Lärm und Luftverschmutzung können einen signifikanten Einfluss auf die psychische Gesundheit ausüben. Aufgrund der teils heterogenen Studienergebnisse und der limitierten Verfügbarkeit von methodisch hochwertigen Längsschnittstudien sind zwingend weitere Untersuchungen notwendig, um tiefere Einblicke in diese Zusammenhänge zu erhalten.

Objectives Transcatheter mitral valve repair (TMVR) by edge-to-edge therapy is an established treatment for severe mitral valve regurgitation (MR). Background Symptomatic and prognostic benefit in functional MR has been shown recently; nevertheless, data on long-term outcomes are sparse. Methods and results We analyzed survival of patients treated with isolated edge-to-edge repair from June 2010 to March 2018 (primarily combined edge-to-edge repair with other mitral valve interventions was excluded) in a retrospective monocentric study. Overall, 627 consecutive patients (47.0% females, 78.6 years in mean) were included. Leading etiology was functional MR (57.4%). Follow-up regarding survival was available in 97.0%. While 97.6% were discharged alive, 75.7% were alive after a 1-year, 54.5% after 3-year, 37.6% after 5-year and 21.7% after 7-year follow-up. Higher logistic Euroscores and comorbidities such as COPD and renal insufficiency were associated with higher in-hospital and 1-year mortality. Importantly, in-hospital survival increased over the years. Conclusions With the present study we established high survival rates at discharge and after 1 year of patients treated with TMVR. This goes along with high implantation numbers, increased interventional experience and a better in-hospital survival over the years. Long-term mortality in turn was substantially influenced by comorbidities.

Tobacco smoking is a leading cause of non-communicable disease globally and is a major risk factor for cardiovascular disease (CVD) and lung disease. Importantly, recent data by the World Health Organizations (WHO) indicate that in the last two decades global tobacco use has significantly dropped, which was largely driven by decreased numbers of female smokers. Despite such advances, the use of e-cigarettes and waterpipes (shisha, hookah, narghile) is an emerging trend, especially among younger generations. There is growing body of evidence that e-cigarettes are not a harm-free alternative to tobacco cigarettes and there is considerable debate as to whether e-cigarettes are saving smokers or generating new addicts. Here, we provide an updated overview of the impact of tobacco/waterpipe (shisha) smoking and e-cigarette vaping on endothelial function, a biomarker for early, subclinical, atherosclerosis from human and animal studies. Also their emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and the circadian clock are summarized. We briefly discuss heat-not-burn tobacco products and their cardiovascular health effects. We discuss the impact of the toxic constituents of these products on endothelial function and subsequent CVD and we also provide an update on current recommendations, regulation and advertising with focus on the USA and Europe. As outlined by the WHO, tobacco cigarette, waterpipe, and e-cigarette smoking/vaping may contribute to an increased burden of symptoms due to coronavirus disease 2019 (COVID-19) and to severe health consequences., Graphical Abstract Graphical Abstract

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.

The aim of the article is to point out the important role of prevention and reduction of mental stress in the general population and in sensitive groups in the context of the coronavirus disease 2019 (COVID-19) pandemic.This article includes the analysis and evaluation of studies and recommendations from organizations such as the World Health Organization (WHO) that have examined the psychological consequences of epidemics/pandemics on people and their impact on the further course.Fear-related behaviors can adversely affect the course of epidemics. Past outbreaks of infectious diseases (Ebola and Zika virus) have shown that maladaptive behavior, related to increased psychological stress and anxiety, can interfere with the implementation of treatment strategies and actions and can contribute to a further spread. Hereby, strategies for dealing with infectious diseases, that include the suppression of fear, can trigger a vicious circle in which fear and suppression mutually reinforce each other.The COVID-19 pandemic poses an immense challenge to governments, health systems and people, with an uncertain outcome, which is associated with a significant burden of mental health in the population. In line with WHO recommendations, national guidelines and preventive measures should include the psychological consequences, the acceptance and normalization of fears and the promotion of resilience in the population in dealing with COVID-19 in order to counteract a further spread.ZIEL: Das Ziel des Beitrages besteht darin, auf die bedeutsame Rolle der Prävention und Reduktion der psychischen Belastungen in der Allgemeinbevölkerung und in sensiblen Gruppen im Rahmen der Coronavirus-Krankheit-2019 (COVID-19) -Pandemie hinzuweisen.Der vorliegende Beitrag umfasst die Analyse und Bewertung von Studien und Empfehlungen von Organisationen wie der Weltgesundheitsorganisation (WHO), die die bevölkerungsbezogenen psychischen Auswirkungen von Epi-/Pandemien und deren Einfluss auf den weiteren Verlauf untersucht haben.Angstbedingte Verhaltensweisen können sich negativ auf den Verlauf von Epidemien auswirken. Im Rahmen vergangener Ausbrüche von Infektionskrankheiten (Ebola- und Zika-Virus) konnte ermittelt werden, dass maladaptive Verhaltensweisen, bedingt durch erhöhte psychische Belastungen und Ängste, die Implementierung von Behandlungsstrategien und -maßnahmen beeinträchtigen und zu einer stärkeren Ausbreitung beitragen können. Hierbei können Strategien im Umgang mit Infektionskrankheiten, die Verdrängung und Unterdrückung von Ängsten beinhalten, einen Teufelskreis auslösen, wobei Ängste und Verdrängung sich gegenseitig verstärken.Die COVID-19-Pandemie stellt eine immense Herausforderung mit noch ungewissem Ausgang für Regierungen, Gesundheitssysteme und Menschen dar, die mit erheblichen Beeinträchtigungen der psychischen Gesundheit in der Bevölkerung verbunden ist. Im Einklang mit Empfehlungen der WHO sollten nationale Leitlinien und präventive Maßnahmen die psychischen Auswirkungen, die Akzeptanz und Normalisierung von Ängsten und die Förderung von Resilienz in der Bevölkerung im Umgang mit COVID-19 umfassen, um einer weiteren Ausbreitung entgegenwirken zu können.

Zusammenfassung Ziel Das Ziel des Beitrages besteht darin, auf die bedeutsame Rolle der Prävention und Reduktion der psychischen Belastungen in der Allgemeinbevölkerung und in sensiblen Gruppen im Rahmen der Coronavirus-Krankheit-2019 (COVID-19) -Pandemie hinzuweisen. Methodik Der vorliegende Beitrag umfasst die Analyse und Bewertung von Studien und Empfehlungen von Organisationen wie der Weltgesundheitsorganisation (WHO), die die bevölkerungsbezogenen psychischen Auswirkungen von Epi-/Pandemien und deren Einfluss auf den weiteren Verlauf untersucht haben. Ergebnisse Angstbedingte Verhaltensweisen können sich negativ auf den Verlauf von Epidemien auswirken. Im Rahmen vergangener Ausbrüche von Infektionskrankheiten (Ebola- und Zika-Virus) konnte ermittelt werden, dass maladaptive Verhaltensweisen, bedingt durch erhöhte psychische Belastungen und Ängste, die Implementierung von Behandlungsstrategien und -maßnahmen beeinträchtigen und zu einer stärkeren Ausbreitung beitragen können. Hierbei können Strategien im Umgang mit Infektionskrankheiten, die Verdrängung und Unterdrückung von Ängsten beinhalten, einen Teufelskreis auslösen, wobei Ängste und Verdrängung sich gegenseitig verstärken. Schlussfolgerungen Die COVID-19-Pandemie stellt eine immense Herausforderung mit noch ungewissem Ausgang für Regierungen, Gesundheitssysteme und Menschen dar, die mit erheblichen Beeinträchtigungen der psychischen Gesundheit in der Bevölkerung verbunden ist. Im Einklang mit Empfehlungen der WHO sollten nationale Leitlinien und präventive Maßnahmen die psychischen Auswirkungen, die Akzeptanz und Normalisierung von Ängsten und die Förderung von Resilienz in der Bevölkerung im Umgang mit COVID-19 umfassen, um einer weiteren Ausbreitung entgegenwirken zu können.

Exposure to traffic noise is associated with stress and sleep disturbances. The World Health Organization (WHO) recently concluded that road traffic noise increases the risk for ischemic heart disease and potentially other cardiometabolic diseases, including stroke, obesity, and diabetes. The WHO report focused on whole-day noise exposure, but new epidemiological and translational field noise studies indicate that nighttime noise, in particular,is an important risk factor for cardiovascular disease (CVD) through increased levels of stress hormones and vascular oxidative stress, leading to endothelial dysfunction and subsequent development of various CVDs. Novel experimental studies found noise to be associated with oxidative stress–induced vascular and brain damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial and neuronal nitric oxide synthase, and vascular/brain infiltration with inflammatory cells. Noise-induced pathophysiology was more pronounced in response to nighttime as compared with daytime noise. This review focuses on the consequences of nighttime noise.

Environmental pollution is a major cause of global mortality and burden of disease. All chemical pollution forms together may be responsible for up to 12 million annual excess deaths as estimated by the Lancet Commission on pollution and health as well as the World Health Organization. Ambient air pollution by particulate matter (PM) and ozone was found to be associated with an all-cause mortality rate of up to 9 million in the year 2015, with the majority being of cerebro- and cardiovascular nature (e.g. stroke and ischemic heart disease). Recent evidence suggests that exposure to airborne particles and gases contributes to and accelerates neurodegenerative diseases. Especially, airborne toxic particles contribute to these adverse health effects. Whereas it is well established that air pollution in the form of PM may lead to dysregulation of neurohormonal stress pathways and may trigger inflammation as well as oxidative stress, leading to secondary damage of cardiovascular structures, the mechanistic impact of PM-induced mitochondrial damage and dysfunction is not well established. With the present review we will discuss similarities between mitochondrial damage and dysfunction observed in the development and progression of cardiovascular disease and neurodegeneration as well as those adverse mitochondrial pathomechanisms induced by airborne PM.

Background Annoyance is a common reaction in populations exposed to environmental noise and is associated with cardiovascular diseases. We investigated for the first time the existence of an association between noise annoyance and atrial fibrillation (AF). Methods and results Cross-sectional data from 14,639 participants of the Gutenberg Health Study were collected between 2007 and 2012. Annoyance from road traffic, aircraft, railways, industrial/construction and neighbourhood noise during daytime and sleep were collected from all participants through questionnaires using a 5-point scale. AF was assessed via self-reported medical history and/or documentation of AF on the study electrocardiogram. 80% of the study participants were annoyed by noise to a certain degree. The major sources of annoyance during daytime and sleep were aircraft, road traffic and neighbourhood noise. We found significant associations between annoyance (per point increase) and AF for aircraft noise annoyance during daytime (odds ratio (OR) 1.04; 95% confidence interval (CI) 1.00–1.08) and during sleep (OR 1.09; 95% CI 1.05–1.13), road traffic noise annoyance during sleep (OR 1.15; 95% CI 1.08–1.22), neighbourhood noise annoyance during daytime (OR 1.14; 95% CI 1.09–1.20) and during sleep (OR 1.14; 95% CI 1.07–1.21), industrial noise annoyance during daytime (OR 1.11; 95% CI 1.04–1.18) and railway noise annoyance during sleep (OR 1.13; 95% CI 1.04–1.22). Different degrees of annoyance were not associated with changes in cardiovascular risk factors. Discussion The results suggest for the first time that noise annoyance is associated with AF. Further studies are warranted to gain insight in the mechanisms underlying the noise-annoyance-disease relationship.

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.

The role of noise as an environmental pollutant and its adverse effects on health are being increasingly recognized. Beyond its direct effects on the auditory system (e.g., hearing loss and tinnitus induced by exposure to high levels of noise), chronic low-level noise exposure causes mental stress associated with known cardiovascular complications. According to recent estimates of the World Health Organization, exposure to traffic noise is responsible for a loss of more than 1.5 million healthy life years per year in Western Europe alone, a major part being related to annoyance, cognitive impairment, and sleep disturbance. Underlying mechanisms of noise-induced mental stress are centered on increased stress hormone levels, blood pressure, and heart rate, which in turn favor the development of cerebrocardiovascular disease such as stroke, arterial hypertension, ischemic heart disease, and myocardial infarction. Furthermore, traffic noise exposure is also associated with mental health symptoms and psychological disorders such as depression and anxiety, which further increase maladaptive coping mechanisms (e.g., alcohol and tobacco use). From a molecular point of view, experimental studies suggest that traffic noise exposure can increase stress hormone levels, thereby triggering inflammatory and oxidative stress pathways by activation of the nicotinamide adenine dinucleotide phosphate oxidase, uncoupling of endothelial/neuronal nitric oxide synthase inducing endothelial and neuronal dysfunction. This review elucidates the mechanisms underlying the relationship between noise exposure and cerebrocardiovascular and psychological disorders, focusing on mental stress signaling pathways including activation of the autonomous nervous system and endocrine signaling and its association with inflammation, oxidative stress, and vascular dysfunction.

Background Traffic noise can induce chronic stress reactions and thereby elevate the risk of cardiovascular disease. The responsible pathophysiological mechanisms are as yet unclear. Methods This review is based on publications retrieved by a selective search in PubMed for epidemiological and experimental studies (2007-2018) on the relation between noise and the risk of cardiovascular disease. The search terms were "noise AND cardiovascular effects" and "noise cardiovascular effects." Results Epidemiological studies have shown that noise caused by air, road, and rail traffic has a dose-dependent association with elevated cardiovascular morbidity and mortality. A current meta-analysis commissioned by the World Health Organization concludes that road-traffic noise elevates the incidence of coronary heart disease by 8% per 10 dB(A) increase starting at 50 dB(A) (95% confidence interval [1,01; 1,15]). Traffic noise at night causes fragmentation of sleep, elevation of stress hormone levels, and oxidative stress. These factors can promote the development of vascular dysfunction (endothelial dysfunction) and high blood pressure, which, in turn, elevate the cardiovascular risk. Conclusion Traffic noise, and air-traffic noise in particular, is an important cardiovascular risk factor that has not been sufficiently studied to date. Preventive measures are needed to protect the population from the harmful effects of noise on health.

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., Graphical abstract Image, graphical abstract

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., Graphical abstract Image 1, Highlights • Noise exposure causes non-auditory cardiovascular/cerebral adverse health effects by oxidative stress and inflammation. • Aircraft noise causes exacerbated adverse effects on blood pressure and endothelial dysfunction in hypertensive mice. • Aircraft noise and hypertension potentiate inflammation, ROS formation and oxidative damage in the brain, vessels and heart. • Aircraft noise and hypertension seem to have enhanced adverse effects on stress responses in different organs.

Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise of the mice caused the most pronounced vascular effects and dysregulation of Foxo3/circadian clock as revealed by next generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein down-regulation, and Nox2 activation. NGS revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, night-time aircraft noise increased oxidative stress, and inflammation biomarkers in serum. Conclusion Aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce night-time aircraft noise are warranted.