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Mitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now.We enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010-03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p 0.001) at 30 days and in 36.6% (p 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53-5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29-2.94], p = 0.001) independently in both etiologies of MR.TMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.

Zusammenfassung Hintergrund Die Sterblichkeit bei COVID-19 ist in Anwesenheit kardiopulmonaler Komorbiditäten erhöht. Luftverschmutzung ist ebenfalls mit einer erhöhten Sterblichkeit assoziiert, v. a. vermittelt durch kardiopulmonale Erkrankungen. Beobachtungen zu Beginn der COVID-19-Pandemie zeigten, dass die Sterblichkeit bei COVID-19 v. a. in Regionen mit stärkerer Luftverschmutzung erhöht ist. Ungeklärt ist der Einfluss von Luftverschmutzung für den Krankheitsverlauf bei COVID-19. Methode Es wurde eine selektive Literaturrecherche von Studien bis Anfang April 2021 in PubMed zum Zusammenhang von Luftverschmutzung und der COVID-19-Mortalität mit den Suchbegriffen „air pollution AND/OR COVID-19/coronavirus/SARS-CoV‑2 AND/OR mortality“ durchgeführt. Ergebnisse Aktuelle Untersuchungen belegen, dass etwa 15 % der weltweiten COVID-19-Todesfälle auf Luftverschmutzung zurückzuführen sind. Der Anteil der luftverschmutzungsbedingten COVID-19-Todesfälle in Europa liegt bei 19 %, in Nordamerika bei 17 % und in Ostasien bei 27 %. Diese Beteiligung der Luftverschmutzung an COVID-19-Todesfällen wurde mittlerweile ebenfalls durch verschiedene Studien aus den USA, Italien und England bestätigt. Luftverschmutzung und COVID-19 führen zu ähnlichen Schäden für das kardiopulmonale System, die möglicherweise den Zusammenhang zwischen Luftverschmutzung und erhöhter COVID-19-Mortalität erklären. Schlussfolgerung Der hier gezeigte Umweltaspekt der COVID-19-Pandemie verlangt danach, dass man verstärkt nach wirksamen Maßnahmen zur Reduzierung anthropogener Emissionen, die sowohl Luftverschmutzung als auch den Klimawandel verursachen, streben sollte.

Zusammenfassung Hintergrund Lärmbelästigung, insbesondere durch Verkehrslärm, stellt ein massives Problem in der Bevölkerung dar und ist mit gesundheitlichen Einschränkungen assoziiert. Ziel der Arbeit Anhand von Daten der bevölkerungsrepräsentativen Gutenberg-Gesundheitsstudie (GHS) werden die Prävalenz der Lärmbelästigung durch verschiedene Quellen sowie relevante Determinanten bestimmt. Material und Methoden Die GHS ist eine populationsbasierte, prospektive Kohortenstudie in Deutschland, die Personen im Alter von 35 bis 74 Jahren einbezieht. 15.010 Probanden aus der Stadt Mainz und dem Landkreis Mainz-Bingen wurden von 2007 bis 2012 befragt, inwiefern sie sich in letzter Zeit durch Flug‑, Straßen‑, Schienen‑, Industrie- und Nachbarschaftslärm belästigt gefühlt haben (Angaben von „überhaupt nicht“ bis „äußerst“). Es wurde jeweils zwischen der Lärmbelästigung am Tag sowie während des Schlafens differenziert. Um die Beziehungen zwischen soziodemographischen Variablen, kardiovaskulären Risikofaktoren sowie Erkrankungen und Lärmbelästigung zu untersuchen, wurden multivariable logistische Regressionsmodelle verwendet. Ergebnisse Etwa 80 % der Probanden fühlten sich durch Lärm belästigt. Fluglärmbelästigung am Tag stellte die vorherrschende Lärmbelästigungsquelle mit der höchsten Prävalenz stark (9,6 %) und äußerst lärmbelästigter Probanden dar (5,4 %), gefolgt von Straßenverkehrs- (stark: 4,0 %; äußerst: 1,6 %) und Nachbarschaftslärmbelästigung (stark: 3,5 %; äußerst: 1,3 %). Die Lärmbelästigung nahm eher mit zunehmender Altersdekade ab. Relevante Determinanten der Lärmbelästigung umfassten mitunter Geschlecht, Alter, sozioökonomischen Status, Depression, Angststörung, Schlafstörung und Vorhofflimmern. Diskussion Lärmbelästigung betrifft einen Großteil der Bevölkerung und ist assoziiert mit soziodemographischen Variablen und kardiovaskulären Risikofaktoren sowie Erkrankungen.

Foundry workers are exposed to numerous occupational health hazards, which may result in increased risk of cancer, respiratory disease, and other diseases. Oxidative stress is known to be involved in the pathogenesis of such diseases. The present study aimed to investigate the association between multiple occupational exposures in foundry workers and expression of deoxyribonucleic acid (DNA) repair genes as a biomarker of oxidative DNA damage. The study sample comprised 17 foundry workers and 27 matched control subjects. Expression of 8-oxoguanine DNA glycosylase-1 (OGG1), inosine triphosphate pyrophosphate (ITPA), and MutT homolog 1 (MTH1) in peripheral blood was examined using the real-time polymerase chain reaction method. Air sampling to determine exposure to metal-rich particulate matter and measurement of extremely low-frequency electromagnetic fields (ELF-EMFs) were conducted according to the National Institute for Occupational Safety and Health standard methods. Personal air sampling revealed that occupational exposure to particulate matter exceeded the threshold limit values (TLVs) in 76% of the workstations, whereas ELF-EMF exposure appeared to be lower than the TLV. ITPA was significantly upregulated in foundry workers compared with control subjects, whereas no significant difference was observed for OGG1 and MTH1. Moreover, ITPA was strongly and positively correlated with the concentration of metal-rich particulate matter in foundry workers. No significant correlation was found between ELF-EMF exposure and expression of DNA repair genes. DNA repair gene expression may be a sensitive biomarker for occupational exposures, which suggests an involvement of oxidative stress in metal-induced toxicity. Further studies are needed to determine the role of DNA repair gene expression in response to occupational/environmental hazards.

Aims To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome. Methods and Results The study sample comprised 15,010 individuals aged 35–74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P prediabetes 1.20, 95% CI 1.07–1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01–1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76–2.51, P P P Conclusion Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.

Takotsubo Syndrome (TTS) is characterized by a transient left ventricular dysfunction recovering spontaneously within days or weeks. Although the pathophysiology of TTS remains obscure, there is growing evidence suggesting TTS to be associated with increased production of reactive oxygen species (ROS), which may be involved in causing transient coronary and peripheral endothelial dysfunction leading to a transient impairment of myocardial contraction due to stunning (apical ballooning). Endothelial dysfunction is mainly caused by decreased vascular and myocardial nitric oxide bioavailability in response to increased ROS production. Accordingly, studies in humans and animal models demonstrated increased myocardial dihydroethidium staining of the myocardium in endomyocardial biopsy specimens, increased levels of hydrogen peroxide and malondialdehyde as well as reduced glutathione levels compatible with increased oxidative stress. As significant superoxide sources the mitochondria and the NADPH oxidase isoform NOX-4 and the NOX-2 regulating cytosolic subunit p67phox have been identified. Treatment with antioxidants such as sodium hydrosulfide reduced superoxide production in mitochondria and reduced expression of NOX-4 and p67phox, respectively. The presence of superoxide and nitric oxide also provides the basis for the concept of nitro-oxidative as well as nitrosative stress in TTS.

Several studies have shown that tea consumption is associated with beneficial effects on human health, which is mainly explained by the antioxidant properties of tea. However, evidence on the effect of nutrition interventions on oxidative stress in an occupational setting is limited. Therefore, the present study aimed to investigate the effect of tea consumption on oxidative stress in noise-exposed metal press workers. The study sample comprised 24 metal press workers and 24 age-matched control subjects. Metal press workers were assigned to the intervention group consisting of a glass of jujube tea and a portion of raisins per day for 4 weeks. Full-shift noise dosimetry was performed to measure noise exposure with average noise levels of 89.91 ± 2.92 dB for metal press workers and 61.54 ± 1.03 dB for control subjects. Elevated levels of baseline oxidative stress were observed in metal press workers compared with control subjects as indicated by significantly decreased levels of total antioxidant capacity (TAC) (P = 0.026) and total thiol groups (TTG) (P = 0.0001), whereas no significant difference was observed in case of malondialdehyde (MDA). Intervention with jujube tea and raisins in metal press workers led to a decrease of oxidative stress as displayed by increased levels of TAC and TTG (P = 0.0001) as well as decreased levels of MDA (P = 0.012). Moreover, the intervention significantly altered expression of repair genes in metal press workers as demonstrated by decreased levels of OGG1 (P = 0.0002) and ITPA (P = 0.009), whereas no significant difference was observed in case of MTH1. These data suggest that regular tea consumption may protect occupational noise-exposed subjects from oxidative damages.

Background Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited. Methods Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed. Results Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12–2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00–2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15–9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021). Conclusion In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit. Graphic abstract

We estimated the association between outdoor light at night at the residence and risk of coronary heart disease (CHD) within a prospective cohort of older adults in Hong Kong.Over a median of 11 years of follow-up, we identified 3772 incident CHD hospitalizations and 1695 CHD deaths. Annual levels of outdoor light at night at participants' residential addresses were estimated using time-varying satellite data for a composite of persistent night-time illumination at ∼1 km2 scale. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between outdoor light at night at the residence and risk of CHD. The association between light at night and incident CHD hospitalization and mortality exhibited a monotonic exposure-response function. An interquartile range (IQR) (60.0 nW/cm2/sr) increase in outdoor light at night was associated with an HR of 1.11 (95% CI: 1.03, 1.18) for CHD hospitalizations and 1.10 (95% CI: 1.00, 1.22) for CHD deaths after adjusting for both individual and area-level risk factors. The association did not vary across strata of hypothesized risk factors.Among older adults, outdoor light at night at the residence was associated with a higher risk of CHD hospitalizations and deaths. We caution against causal interpretation of these novel findings. Future studies with more detailed information on exposure, individual adaptive behaviours, and potential mediators are warranted to further examine the relationship between light at night and CHD risk.

Aims Nighttime aircraft noise exposure has been associated with increased risk of hypertension and myocardial infarction, mechanistically linked to sleep disturbance, stress, and endothelial dysfunction. It is unclear, whether the most widely used metric to determine noise exposure, equivalent continuous sound level (Leq), is an adequate indicator of the cardiovascular impact induced by different noise patterns. Methods and results In a randomized crossover study, we exposed 70 individuals with established cardiovascular disease or increased cardiovascular risk to two aircraft noise scenarios and one control scenario. Polygraphic recordings, echocardiography, and flow-mediated dilation (FMD) were determined for three study nights. The noise patterns consisted of 60 (Noise60) and 120 (Noise120) noise events, respectively, but with comparable Leq, corresponding to a mean value of 45 dB. Mean value of noise during control nights was 37 dB. During the control night, FMD was 10.02 ± 3.75%, compared to 7.27 ± 3.21% for Noise60 nights and 7.21 ± 3.58% for Noise120 nights (P, Graphical Abstract

Significance: According to the World Health Organization, noncommunicable diseases are the globally leading cause of mortality. Recent Advances: About 71% of 56 million deaths that occurred worldwide are due to noncommunicable cardiovascular risk factors, including tobacco smoking, unhealthy diets, lack of physical activity, overweight, arterial hypertension, diabetes, and hypercholesterolemia, which can be either avoided or substantially reduced. Critical Issues: Thus, it is estimated that 80% of premature heart disease, stroke, and diabetes can be prevented. More recent evidence indicates that environmental stressors such as noise and air pollution contribute significantly to the global burden of cardiovascular disease. In the present review, we focus primarily on important environmental stressors such as transportation noise and air pollution. We discuss the pathophysiology of vascular damage caused by these environmental stressors, with emphasis on early subclinical damage of the vasculature such as endothelial dysfunction and the role of oxidative stress. Future Directions: Lower legal thresholds and mitigation measures should be implemented and may help to prevent vascular damage.

ZusammenfassungImmer 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.

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.

Background Environmental noise exposure has been associated with increased cardiovascular morbidity and mortality. Recently, noise annoyance was shown to induce atrial fibrillation, which was accompanied by significantly increased levels of midregional pro atrial natriuretic peptide (MR-proANP). Therefore, the aim of the present study was to analyze the association between noise annoyance, MR-proANP, incident cardiovascular events, and all-cause mortality. Methods Levels of MR-proANP were measured in the first 5000 participants of the population-based Gutenberg Health Study. Annoyance was assessed separately for aircraft, road traffic, railway, neighborhood, and industrial/construction noise during the day and sleep. Results In cross-sectional analyses, aircraft noise annoyance during day and sleep, industrial/construction noise annoyance during day, and railway noise annoyance during sleep were independently associated with increased levels of MR-proANP after multivariable adjustment. After a 5-year follow-up period, there were 43 cases of incident atrial fibrillation and 103 of incident cardiovascular disease (comprising atrial fibrillation, coronary artery disease, myocardial infarction, heart failure, or stroke). Moreover, there were 301 deaths after a mean follow-up of 7.42 ± 1.66 years. An odds ratio (OR) of 2.82 ([95% confidence interval (CI) 1.86; 4.35], p p = 0.0046) for incident cardiovascular disease per 1-standard deviation (SD) increase in MR-proANP levels were found. A 36% (hazard ratio: 1.36 [95% CI 1.19; 1.55], p Conclusions Noise annoyance may contribute to cardiovascular morbidity and mortality and is characterized by increased levels of MR-proANP. Graphic abstract

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.

Background Cardiac amyloidosis (CA) is increasingly recognized as an underlying cause of heart failure with preserved ejection fraction (HFpEF), associated with high morbidity and mortality. However, most studies, solely investigated the prevalence of CA in special subgroups including HFpEF and severe aortic valve disease. Purpose With the present study we sought to investigate prevalence of different phenotypes of CA in an all comer-population of patients with non-ischaemic heart failure (HF) and to analyze the impact of CA on all-cause mortality. Methods The My Biopsy HF-Study (German clinical trials register number: 22178) is a retrospective monocentric study investigating the underlying etiology of HF in an all-comer population of patients with HF of unknown etiology. Patients presenting with symptoms of HF at the University Medical Centre between 14/10/2012 and 01/03/2021, who underwent endomyocardial biopsy (EMB) were enrolled in the present study. Ischaemic HF and valvular HF were ruled out prior to EMB. Specimens were sent for further examination to a specialized laboratory approved by the Food and Drug Administration Results Between October 2012 and March 2021, 767 patients (71.6% men) with HF of unknown etiology were included. Mean age at the time of presentation was 55.4 years (±14.4). Altogether, 72.5% of the patients presented with HF with reduced ejection fraction (HFrEF), 7.1% were diagnosed with HF with mid-range ejection fraction (HFmrEF) and 20.4% with HFpEF. Based on histological examination and genotyping, CA was diagnosed in 44 (5.7%) patients (immunglobulin light chain [AL] CA: 15 patients; variant transthyretin [ATTRv] CA: 6 patients; wild type transthyretin [ATTRwt] CA: 21 patients; de novo CA: 2 patients). Patients with CA were older compared with patients without CA (69.4±11.4 vs. 54.1±14.5; p Conclusions Among patients presenting with HF of unknown etiology, including patients with HFpEF, HFmrEF and HFrEF, cardiac amyloidosis is the underlying cause of HF in 5.7% of patients and is independently associated with all-cause mortality. Funding Acknowledgement Type of funding sources: None.

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., Graphical abstract Image 1, Highlights • Noise exposure induces a pro-thrombo-inflammatory phenotype in mouse plasma. • Aircraft noise increases leukocyte-endothelium interactions in dorsal microvessels. • Noise decreases segmental blood flow/red blood cell velocity in dorsal microvessels. • Noise increases cerebral microvascular dysfunction and oxidative stress. • Nox2 deficiency (gp91phox-/y) improves noise-induced adverse effects.

It is unclear whether night-time noise events, including from aeroplanes, could trigger a cardiovascular death. In this study, we investigate the potential acute effects of aircraft noise on mortality and the specific role of different night-time exposure windows by means of a case-crossover study design.We selected 24 886 cases of death from cardiovascular disease (CVD) from the Swiss National Cohort around Zürich Airport between 2000 and 2015. For night-time deaths, exposure levels 2 h preceding death were significantly associated with mortality for all causes of CVD [OR = 1.44 (1.03-2.04) for the highest exposure group (LAeq50 dB vs.20 dB)]. Most consistent associations were observed for ischaemic heart diseases, myocardial infarction, heart failure, and arrhythmia. Association were more pronounced for females (P = 0.02) and for people living in areas with low road and railway background noise (P = 0.01) and in buildings constructed before 1970 (P = 0.36). We calculated a population attributable fraction of 3% in our study population.Our findings suggest that night-time aircraft noise can trigger acute cardiovascular mortality. The association was similar to that previously observed for long-term aircraft noise exposure.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is posing a global public health burden. These consequences have been shown to increase the risk of mental distress, but the underlying protective and risk factors for mental distress and trends over different waves of the pandemic are largely unknown. Furthermore, it is largely unknown how mental distress is associated with individual protective behavior. Three quota samples, weighted to represent the population forming the German COVID-19 Snapshot Monitoring study (24 March and 26 May 2020, and 9 March 2021 with &gt, 900 subjects each), were used to describe the course of mental distress and resilience, to identify risk and protective factors during the pandemic, and to investigate their associations with individual protective behaviors. Mental distress increased slightly during the pandemic. Usage of cognitive reappraisal strategies, maintenance of a daily structure, and usage of alternative social interactions decreased. Self-reported resilience, cognitive reappraisal strategies, and maintaining a daily structure were the most important protective factors in all three samples. Adherence to individual protective behaviors (e.g., physical distancing) was negatively associated with mental distress and positively associated with frequency of information intake, maintenance of a daily structure, and cognitive reappraisal. Maintaining a daily structure, training of cognitive reappraisal strategies, and information provision may be targets to prevent mental distress while assuring a high degree of individual protective behaviors during the COVID-19 pandemic. Effects of the respective interventions have to be confirmed in further studies.

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH). Methods: 15,010 subjects (35–74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up. Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) over prediabetes (17.8%) to T2DM (23.8%). Prediabetes and T2DM were associated with increased LV mass index (prediabetes: β1.3 (95% CI 0.78–1.81), p &lt, 0.0001, T2DM: β2.37 (95% CI 1.81, 2.92), p &lt, 0.0001) independent of age, sex, and cardiovascular risk factors (CVRF). The frequency of LVH was related to the presence of T2DM (prevalence ratio (PR)T2DM 1.2 (95% CI 1.06–1.35), p = 0.0038). T2DM was related to mortality independent of age, sex, and CVRF regardless of LVH (hazard ratio (HR)T2DM-LVH 2.67 (95% CI 1.94–3.66), p &lt, HRT2DM-noLVH 1.59 (95% CI 1.29–1.96), p &lt, 0.0001), prediabetes was only associated with outcome in individuals with LVH independent of age and sex (HRprediabetes-LVH 1.51 (95% CI 1.01–2.25), p = 0.045). Neither T2DM nor prediabetes were predictors of incident LVH after adjustment for clinical covariates. Conclusions: Prediabetes and T2DM promote alterations of cardiac geometry. T2DM and particularly the coprevalence of T2DM with LVH substantially reduce life expectancy. These findings highlight the need for new therapeutic and screening approaches to prevent and detect cardiometabolic diseases at an early stage.

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 P =0.0021) in a fully adjusted model. Combination of both, performing endurance training and having stiffness index values below median, resulted in the best survival. In contrast, subjects with elevated stiffness index at baseline without any endurance activities demonstrated the worst survival. Conclusions In this population representative sample, a differential impact of domains of self‐reported PA on AS was demonstrated. Our data strengthen the importance of regular endurance PA to induce a reduction of AS, which, in turn, may improve cardiovascular prognosis. We also report deleterious effects of intense occupational PA on stiffness index, a finding that needs further confirmation by larger prospective trials.

Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD.

The aim of this study was to compare patients with transcatheter aortic valve replacement (TAVR) receiving new generation prostheses SAPIEN 3 (S3, Edwards Lifesc.) and Evolut R (ER, Medtronic Inc.) in terms of periprocedural and long-term outcome. Our retrospective, single-center analysis included 359 consecutive patients with severe aortic stenosis who underwent TAVR with S3 or ER from 2014–2016 (mean age 82 ± 7 years, 47% male, mean EuroSCORE II 8.0 ± 8%, mean follow-up 3.8 years). Device Success was equal (S3 93.0% vs. ER 92.4%, p = 0.812). We report a 30-day mortality of 2.8% in the S3 group, and 2.1% in the ER group (p = 0.674). There was no difference in stroke, conversion to open surgery, vascular and bleeding complications or myocardial infarction. While prosthesis mean gradients were higher with S3 (12.0 mmHg vs. 8.2 mmHg, p &lt, 0.001), there was a trend to less paravalvular regurgitation (PVR moderate or severe: 1% vs. 3.6%, p = 0.088). All-cause mortality up to 5 years did not show a difference (mean survival S3 3.5 ± 0.24 years, ER 3.3 ± 0.29 years, p = 0.895). Independent predictors of long-term mortality were impaired LVEF, chronic kidney injury, peripheral artery disease, malignant tumor and periprocedural stroke. New generation TAVR valves offer an excellent implant and outcome success rate. Long-term survival was independent of prostheses choice and mainly attributed to comorbidities and complications.

Aims Electronic (e)-cigarettes have been marketed as a ‘healthy’ alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms. Methods and results Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow-mediated dilation. In mice, e-cigarette vapour without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation, and lipid peroxidation than vapour containing nicotine. These effects of e-cigarette vapour were largely absent in mice lacking phagocytic NADPH oxidase (NOX-2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e-cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX-2-dependent effects of e-cigarette vapour using in vitro blood vessel incubation. Conclusions E-cigarette vapour exposure increases vascular, cerebral, and pulmonary oxidative stress via a NOX-2-dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e-cigarettes have the potential to induce marked adverse cardiovascular, pulmonary, and cerebrovascular consequences. Since e-cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit their health risks.

Die Luftverschmutzung in der Umgebung und in Haushalten ist ein groses Gesundheitsproblem, das weltweit jahrlich fur mittlerweile mehr als 8 Mio. vermeidbare vorzeitige Todesfalle und innerhalb Europas fur knapp 800.000 solche Todesfalle verantwortlich ist. Dieser Beitrag befasst sich mit den Auswirkungen von Luftverschmutzung auf das Herz-Kreislauf-System. Es wurde eine Literaturrecherche epidemiologischer und experimenteller Studien zum Zusammenhang von Luftverschmutzung und Herz-Kreislauf-Erkrankungen durchgefuhrt. Epidemiologische Studien zeigen, dass Luftverschmutzung durch Feinstaub („particulate matter“, PM2.5 und PM10) mit erhohter kardiovaskularer Morbiditat und Mortalitat assoziiert ist. Hierfur verantwortlich sind hauptsachlich durch Feinstaub ausgeloste oder verschlimmerte Herz-Kreislauf-Erkrankungen, wie koronare Herzerkrankung, Herzinfarkt, Herzinsuffizienz, Schlaganfall, Hypertonie und auch Diabetes. Experimentelle Untersuchungen zeigen, dass Feinstaubpartikel uber einen Transitionsprozess in die Blutbahn gelangen und die Bildung reaktiver Sauerstoffspezies in der Gefaswand stimulieren, wodurch atherosklerotische Veranderungen begunstigt werden und so das kardiovaskulare Risiko steigt. Insbesondere aufgrund von neuesten Berechnungen stellt die Luftverschmutzung einen wichtigen Risikofaktor fur die Entstehung von Herz-Kreislauf-Erkrankungen dar. Dies macht praventive Masnahmen, z. B. eine Absenkung der Grenzwerte fur Luftschadstoffe, insbesondere fur PM2.5 von 25 µg/m3 auf die von der WHO (World Health Organization) empfohlenen 10 µg/m3 erforderlich.

Background Higher, but also lower resting heart rate (HR), has been associated with increased cardiovascular events and mortality. Little is known about the interplay between HR, cardiovascular risk factors, concomitant diseases, vascular (endothelial) function, neurohormonal biomarkers, and all-cause mortality in the general population. Thus, we aimed to investigate these relationships in a population-based cohort. Methods 15,010 individuals (aged 35–74 at enrolment in 2007–2012) from the Gutenberg Health Study were analyzed. Multivariable regression modeling was used to assess the relation between the variables and conditional density plots were generated for cardiovascular risk factors, diseases, and mortality to show their dependence on HR. Results There were 714 deaths in the total sample at 7.67 ± 1.68 years of follow-up. The prevalence of diabetes mellitus, arterial hypertension, coronary and peripheral artery disease, chronic heart failure, and previous myocardial infarction exhibited a J-shaped association with HR. Mortality showed a similar relation with a nadir of 64 beats per minute (bpm) in the total sample. Each 10 bpm HR reduction in HR 64 subjects (Hazard Ratio 1.29; 95% confidence interval 1.19–1.41 per 10 bpm increase in HR). Results found for vascular and neurohormonal biomarkers exhibited a differential picture in subjects with a HR below and above the nadir. Discussion These results indicate that in addition to a higher HR, a lower HR is associated with increased mortality. Electronic supplementary material The online version of this article (10.1007/s00392-019-01466-2) contains supplementary material, which is available to authorized users.

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.

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.

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.

Air pollution in the environment and in households is responsible worldwide for almost 9 million preventable premature deaths per year and almost 800,000 such deaths within Europe. Air pollution therefore shortens life expectancy worldwide by almost 3 years. Smoking, a proven cardiovascular risk factor, shortens the mean life expectancy by 2.2 years. Epidemiological studies have shown that air pollution from fine and coarse particulate matter is associated with increased cardiovascular morbidity and mortality. Responsible for this are mainly cardiovascular diseases, such as coronary heart disease, heart attack, heart failure, stroke, hypertension and also diabetes, which are mainly caused or aggravated by fine particulate matter. After inhalation fine particulate matter can reach the brain directly and also reach the bloodstream via a transition process. There, the particles are absorbed by the blood vessels where they stimulate the formation of reactive oxygen species (ROS) in the vascular wall. They therefore promote the formation of atherosclerotic changes and in this way increase the cardiovascular risks, especially an increase in chronic ischemic heart disease and stroke. Recent studies also reported that in coronavirus disease 2019 (COVID-19) patients a high degree of air pollution is correlated with severe disease courses with cardiovascular complications and pulmonary diseases. This necessitates preventive measures, such as lowering of the upper limits for air pollutants. Individual measures to mitigate the health consequences of fine particulate matter are also discussed.Die Luftverschmutzung in der Umgebung und in Haushalten ist weltweit jährlich für mittlerweile knapp 9 Mio. vermeidbare, vorzeitige Todesfälle und innerhalb Europas für knapp 800.000 solcher Todesfälle verantwortlich. Die Luftverschmutzung verkürzt somit weltweit die Lebenserwartung um knapp 3 Jahre. Das Rauchen, ein nachgewiesener Herz-Kreislauf-Risiko-Faktor, verkürzt die mittlere Lebenserwartung um 2,2 Jahre. Epidemiologische Studien zeigen, dass Luftverschmutzung durch Feinstaub mit erhöhter kardiovaskulärer Morbidität und Mortalität assoziiert ist. Hierfür verantwortlich sind hauptsächlich durch Feinstaub ausgelöste oder verschlimmerte Herz-Kreislauf-Erkrankungen, wie koronare Herzkrankheit (KHK), Herzinfarkt, Herzinsuffizienz, Schlaganfall, Hypertonie und auch Diabetes. Feinstaubpartikel können nach Inhalation zum einen direkt ins Gehirn und zum anderen über einen Transitionsprozess in die Blutbahn gelangen. Dort werden sie in die Blutgefäße aufgenommen, wo sie die Bildung reaktiver Sauerstoffspezies (ROS) in der Gefäßwand stimulieren. Damit begünstigen sie die Entstehung atherosklerotischer Veränderungen und steigern so das kardiovaskuläre Risiko, insbesondere eine Zunahme an chronisch-ischämischer Herzerkrankung und Schlaganfall. Neuere Untersuchungen berichten, dass bei COVID-19(„coronavirus disease 2019“)-Patienten ein hoher Grad an Luftverschmutzung mit schweren Krankheitsverläufen mit kardiovaskulären Komplikationen und Lungenerkrankungen korreliert. Dies macht präventive Maßnahmen, wie z. B. eine Absenkung der Grenzwerte für Luftschadstoffe, erforderlich. Individuelle Maßnahmen, um die gesundheitlichen Folgen von Feinstaub abzumildern, werden ebenfalls diskutiert.

The world’s population is estimated to reach 10 billion by 2050 and 75% of this population will live in cities. Two-third of the European population already live in urban areas and this proportion continues to grow. Between 60% and 80% of the global energy use is consumed by urban areas, with 70% of the greenhouse gas emissions produced within urban areas. The World Health Organization states that city planning is now recognized as a critical part of a comprehensive solution to tackle adverse health outcomes. In the present review, we address non-communicable diseases with a focus on cardiovascular disease and the urbanization process in relation to environmental risk exposures including noise, air pollution, temperature, and outdoor light. The present review reports why heat islands develop in urban areas, and how greening of cities can improve public health, and address climate concerns, sustainability, and liveability. In addition, we discuss urban planning, transport interventions, and novel technologies to assess external environmental exposures, e.g. using digital technologies, to promote heart healthy cities in the future. Lastly, we highlight new paradigms of integrative thinking such as the exposome and planetary health, challenging the one-exposure-one-health-outcome association and expand our understanding of the totality of human environmental exposures., Graphical Abstract

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G−Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

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.

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.

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.

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., Graphical abstract Image 1, Highlights • Exposure to (traffic) noise causes non-auditory (indirect) cardiovascular and cerebral health harms via neuronal activation. • Noise activates the HPA axis and sympathetic nervous system increasing levels of stress hormones, vasoconstrictors and ROS. • Noise induces inflammation and stimulates several ROS sources leading to cerebral and cardiovascular oxidative damage. • Noise leads to eNOS and nNOS uncoupling contributing to cardiometabolic disease and cognitive impairment.

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.