Burden of disease in Germany attributed to ambient particulate matter pollution : Findings from the Global Burden of Disease Study 2019.

INTRODUCTION: Ambient fine particulate matter pollution with a diameter less than 2.5 micrometers (PM2.5) is a significant risk factor for chronic noncommunicable diseases (NCDs), leading to a substantial disease burden, decreased quality of life, and deaths globally. This study aimed to investigate the disease and mortality burdens attributed to PM2.5 in Germany in 2019. METHODS: Data from the Global Burden of Disease (GBD) Study 2019 were used to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to ambient PM2.5 pollution in Germany. RESULTS: In 2019, ambient PM2.5 pollution in Germany was associated with significant health impacts, contributing to 27,040 deaths (2.82% of total deaths), 568,784 DALYs (2.09% of total DALYs), 135,725 YLDs (1.09% of total YLDs), and 433,058 YLLs (2.92% of total YLLs). The analysis further revealed that cardiometabolic and respiratory conditions, such as ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus, were the leading causes of mortality and disease burden associated with ambient PM2.5 pollution in Germany from 1990-2019. Comparative assessments between 1990 and 2019 underscored ambient PM2.5 as a consistent prominent risk factor, ranking closely with traditional factors like smoking, arterial hypertension, and alcohol use contributing to deaths, DALYs, YLDs, and YLLs. CONCLUSION: Ambient PM2.5 pollution is one of the major health risk factors contributing significantly to the burden of disease and mortality in Germany, emphasizing the urgent need for targeted interventions to address its substantial contribution to chronic NCDs.

Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.

CD40L-CD40-TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L-CD40-TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L-CD40-TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L-CD40-TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Burden of Disease Due to Air Pollution in Afghanistan-Results from the Global Burden of Disease Study 2019.

INTRODUCTION: Air pollution is a significant risk factor for a range of diseases and leads to substantial disease burden and deaths worldwide. This study aimed to investigate the burden of disease in Afghanistan attributed to air pollution in 2019. METHODS: Data from the Global Burden of Disease (GBD) Study 2019 were used to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to air pollution in Afghanistan. RESULTS: In 2019, air pollution in Afghanistan was associated with significant health impacts, and contributed to 37,033 deaths (14.72% of total deaths), 1,849,170 DALYs (10.80% of total DALYs), 76,858 YLDs (2.07% of total YLDs), and 1,772,311 YLLs (13.23% of total YLLs). The analysis further revealed that lower respiratory infections, neonatal disorders, ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus were the leading causes of mortality and disease burden associated with air pollution in Afghanistan from 1990 to 2019. Comparative assessments between 1990 and 2019 underscored air pollution as a consistent prominent risk factor that ranked closely with other risk factors, like malnutrition, high blood pressure, and dietary risks, in contributing to deaths, DALYs, YLDs, and YLLs. In a comparative country analysis for the year 2019, Afghanistan emerged as having a substantial burden of disease due to air pollution, closely mirroring other high-burden nations like China, India, Pakistan, and Bangladesh. DISCUSSION: Air pollution is one of the major health risk factors that significantly contribute to the burden of disease in Afghanistan, which emphasizes the urgent need for targeted interventions to address this substantial public health threat.

Health position paper and redox perspectives - Disease burden by transportation noise.

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

Human epithelial lung cell toxicity assessment of collected graphite particles from an iron casting industry (in vitro study).

Workers in the iron casting industries are exposed to various chemicals, especially graphite in furnace process. This study aims to investigate the toxic effects of graphite particles on human lung cells. Particle characteristics were confirmed by electron microscope and light scattering. Cell viability and oxidative stress markers were measured. The expression of oxidative repair genes, namely OGG1, MTH1, and ITPA, was evaluated. The average particle size was determined to be 172.1 ± 11.96 nm. The median inhibition concentration (IC50) of graphite particles was 46.75 µg/mL. Notably, 25 and 50 µg/mL concentrations resulted in significant GSH depletion and MDA production. The high concentration of graphite particles (200 µg/mL) led to OGG1 suppression and increased MTH1 expression. Based on these findings, graphite exposure may induce toxicity in human lung cells by increasing oxidative stress. Further research is necessary to fully understand the mechanisms underlying graphite toxicity.

The role of acrolein for E-cigarette vapour condensate mediated activation of NADPH oxidase in cultured endothelial cells and macrophages.

Electronic cigarettes (E-cigarettes) have recently become a popular alternative to traditional tobacco cigarettes. Despite being marketed as a healthier alternative, increasing evidence shows that E-cigarette vapour could cause adverse health effects. It has been postulated that degradation products of E-cigarette liquid, mainly reactive aldehydes, are responsible for those effects. Previously, we have demonstrated that E-cigarette vapour exposure causes oxidative stress, inflammation, apoptosis, endothelial dysfunction and hypertension by activating NADPH oxidase in a mouse model. To better understand oxidative stress mechanisms, we have exposed cultured endothelial cells and macrophages to condensed E-cigarette vapour (E-cigarette condensate) and acrolein. In both endothelial cells (EA.hy 926) and macrophages (RAW 264.7), we have observed that E-cigarette condensate incubation causes cell death. Since recent studies have shown that among toxic aldehydes found in E-cigarette vapour, acrolein plays a prominent role, we have incubated the same cell lines with increasing concentrations of acrolein. Upon incubation with acrolein, a translocation of Rac1 to the plasma membrane has been observed, accompanied by an increase in oxidative stress. Whereas reactive oxygen species (ROS) formation by acrolein in cultured endothelial cells was mainly intracellular, the release of ROS in cultured macrophages was both intra- and extracellular. Our data also demonstrate that acrolein activates the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and, in general, could mediate E-cigarette vapour-induced oxidative stress and cell death. More mechanistic insight is needed to clarify the toxicity associated with E-cigarette consumption and the possible adverse effects on human health.

Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure.

AIMS: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment. METHODS AND RESULTS: Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. CONCLUSION: Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.

Traffic noise, e.g. from aircraft, significantly contributes to an increased risk of cardiovascular or metabolic diseases in the general population by brain-dependent stress reactions leading to higher levels of circulating stress hormones and vasoconstrictors, all of which cause hypertension, oxidative stress, and inflammation. With the present experimental studies, we provide for the first time molecular mechanisms responsible for successful noise mitigation: Physical exercise, intermittent fasting, and pharmacological activation of the adenosine monophosphate-activated protein kinase (AMPK), a metabolic master regulator protein, prevent cardiovascular damage caused by noise exposure, such as hypertension, endothelial dysfunction, and reactive oxygen species formation (e.g. free radicals) and inflammation.These beneficial mitigation manoeuvers are secondary to an activation of the endothelial AMPK, thereby mimicking the antidiabetic drug metformin.

E-cigarette effects on vascular function in animals and humans.

Smoking tobacco cigarettes is a significant (cardiovascular) health risk factor. Although the number of tobacco cigarette users declined over the last decades, shisha smoking and e-cigarette vaping partially compensated for this health benefit. E-cigarettes may create highly addicted dual users (vaping and smoking). E-cigarettes seem not to represent a healthier alternative to tobacco smoking, although they may be less harmful. E-cigarette vaping causes oxidative stress, inflammation, endothelial dysfunction, and associated cardiovascular sequelae. This is primarily due to a significant overlap of toxic compounds in the vapor compared to tobacco smoke and, accordingly, a substantial overlap of pathomechanistic features between vaping and smoking. Whereas the main toxins in vapor are reactive aldehydes such as formaldehyde and acrolein, the toxic mixture in smoke is more complex, comprising particulate matter, reactive gases, transition metals, volatile organic compounds, and N-nitrosamines. However, it seems that both lifestyle drugs impair endothelial function to a quite similar extent, which may be due to the role of oxidative stress as the central pathomechanism to mediate endothelial dysfunction and vascular damage. Finally, the main selling argument for e-cigarette use that they help to quit smoking and get rid of nicotine addiction may be false because it seems that e-cigarettes instead trigger the opposite-younger entrance age and more frequent use. With our review, we summarize the adverse health impact of tobacco cigarettes and e-cigarettes, emphasizing the detrimental effects on endothelial function and cardiovascular health.

Tobacco smoking and vascular biology and function: evidence from human studies.

Tobacco cigarette smoking is among the most complex and least understood health risk factors. A deeper insight into the pathophysiological actions of smoking exposure is of special importance as smoking is a major cause of chronic non-communicable diseases, in particular of cardiovascular disease as well as risk factors such as atherosclerosis and arterial hypertension. It is well known that smoking exerts its negative effects on cardiovascular health through various interdependent pathophysiological actions including hemodynamic and autonomic alterations, oxidative stress, inflammation, endothelial dysfunction, thrombosis, and hyperlipidemia. Importantly, impaired vascular endothelial function is acknowledged as an early key event in the initiation and progression of smoking-induced atherosclerosis. Increasing evidence from human studies indicates that cigarette smoke exposure associates with a pathological state of the vascular endothelium mainly characterized by reduced vascular nitric oxide bioavailability due to increased vascular superoxide production. In the present overview, we provide compact evidence on the effects of tobacco cigarette smoke exposure on vascular biology and function in humans centered on main drivers of adverse cardiovascular effects including endothelial dysfunction, inflammation, and oxidative stress.

Chronic cigarette smoking is associated with increased arterial stiffness in men and women: evidence from a large population-based cohort.

BACKGROUND: Cigarette smoking is a threat to global human health and a leading cause of the cardiovascular disease (CVD) morbidity and mortality. Importantly, sex-specific differences in smoking-induced arterial stiffness, an early key event in the development of atherosclerotic CVD, remain still elusive. Thus, this study sought out to investigate sex-specific associations between smoking and measures of arterial stiffness. METHODS AND RESULTS: Overall, 15,010 participants (7584 men and 7426 women aged 35-74 years) of the Gutenberg Health Study were examined at baseline during 2007-2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a standardized computer-assisted interview. Arterial stiffness and wave reflection were determined by stiffness index (SI) and augmentation index (AI). In the total sample, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Median cumulative smoking exposure was 22.0 pack-years in current male smokers and 16.0 in current female smokers. In general, multivariable linear regression models adjusted for a comprehensive set of confounders revealed that smoking status, pack-years of smoking, and years since quitting smoking were dose-dependently associated with markers of arterial stiffness. In sex-specific analyses, these associations were overall more pronounced in men and SI was stronger related to the male sex, whereas differences between men and women in the case of AI appeared to be less substantial. DISCUSSION: The present results indicate that chronic smoking is strongly and dose-dependently associated with increased arterial stiffness in a large population-based cohort regardless of sex but with a stronger association in men.

The association of smoking and smoking cessation with prevalent and incident symptoms of depression, anxiety, and sleep disturbance in the general population.

BACKGROUND: Smoking is a well-established risk factor for chronic non-communicable diseases. However, the relationship between cigarette smoking and the risk of developing mental health conditions remains largely elusive. This study examined the relationship between cigarette smoking as well as smoking cessation and prevalent and incident symptoms of depression, anxiety, and sleep disturbance in the general population. METHODS: In a cohort of 15,010 individuals from the Gutenberg Health Study (aged 35-74 years at enrollment), prevalent (at baseline from 2007 to 2012) and incident symptoms (at follow-up from 2012 to 2017) of depression, anxiety, and sleep disturbance were determined by validated questionnaires and/or medical records. Smoking status, pack-years of smoking in current and former smokers, and years since quitting smoking in former smokers were assessed by a standardized computer-assisted interview. RESULTS: In multivariable logistic regression models with comprehensive adjustment for covariates, smoking status was independently associated with prevalent and incident symptoms of depression (Patient Health Questionnaire-9 ≥ 10), whereas this association was weaker for anxiety (Generalized Anxiety Disorder Scale-2 ≥ 3) and sleep disturbance (Patient Health Questionnaire-9 > 1). Among current and former smokers, smoking ≥30 or ≥10 pack-years, respectively, yielded in general the highest effect estimates. Smoking cessation was weakly associated with the prevalence and incidence of all outcomes, here consistent associations were observed for prevalent symptoms of depression. LIMITATIONS: The observational nature of the study does not allow for causal inferences. CONCLUSIONS: The results of the present study suggest that cigarette smoking is positively and that smoking cessation is negatively associated with symptoms of common mental health conditions, in particular of depression.

Lung cell toxicity of co-exposure to airborne particulate matter and extremely low-frequency magnetic field.

Although the toxic effects of urban airborne particulate matter (PM) have been known on lung cells, there is less attention to co-exposure to PM and extremely low frequency magnetic (ELF-MF) in occupational settings. The present study investigated the influences of PM and ELF-MF co-exposure on toxicity in human lung cells (A549).In this case, total PM (TPM) was evaluated according to NIOSH-0500. The TPM SiO2 and metal contents were determined based on NIOSH-7602 and 7302, respectively. Besides, 900 mG ELF-MF exposure was simulated based on field measurements. The toxicity mechanisms were assessed by examining malondialdehyde, glutathione ratio, gene expression, and DNA strand breaks. Also, the toxicity indicators of the TPM samples were MDA generation, glutathione depletion, and DNA damage, and their impacts were analysed at doses below the LD50 (4 µg).In addition, gene expression of OGG1 and MTH1 was upregulated after TPM exposure at the lowest dose (2 µg). But ITPA was upregulated in the presence of ELF-MF. The co-exposure to TPM and ELF-MF decreased oxidative stress and DNA damage levels compared to a single exposure to TPM.Although the ELF-MF reduced toxicity in response to TPM, this reduction was not lower than the unexposed cells.

Environmental risk factors and cardiovascular diseases: a comprehensive expert review.

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.

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

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 < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 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 < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality. 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.

Right atrium size in the general population.

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

Occupational exposure to metal-rich particulate matter modifies the expression of repair genes in foundry workers.

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.

Long-Term Outcome with New Generation Prostheses in Patients Undergoing Transcatheter Aortic Valve Replacement.

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 < 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.

Smoking and Neuropsychiatric Disease-Associations and Underlying Mechanisms.

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.