Takotsubo Syndrome: Impact of endothelial dysfunction and oxidative stress

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

Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes

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

Noise annoyance and risk of prevalent and incident atrial fibrillation–A sex-specific analysis

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

Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects

Nocturnal train noise exposure has been associated with hypertension and myocardial infarction. It remains unclear whether acute nighttime train exposure may induce subclinical atherosclerosis, such as endothelial dysfunction and other functional and/or biochemical changes. Thus, we aimed to expose healthy subjects to nocturnal train noise and to assess endothelial function, changes in plasma protein levels and clinical parameters. In a randomized crossover study, we exposed 70 healthy volunteers to either background or two different simulated train noise scenarios in their homes during three nights. After each night, participants visited the study center for measurement of vascular function and assessment of other biomedical and biochemical parameters. The three nighttime noise scenarios were exposure to either background noise (control), 30 or 60 train noise events (Noise30 or Noise60), with average sound pressure levels of 33, 52 and 54 dB(A), respectively. Flow-mediated dilation (FMD) of the brachial artery was 11.23 ± 4.68% for control, compared to 8.71 ± 3.83% for Noise30 and 8.47 ± 3.73% for Noise60 (p < 0.001 vs. control). Sleep quality was impaired after both Noise30 and Noise60 nights (p < 0.001 vs. control). Targeted proteomic analysis showed substantial changes of plasma proteins after the Noise60 night, mainly centered on redox, pro-thrombotic and proinflammatory pathways. Exposure to simulated nocturnal train noise impaired endothelial function. The proteomic changes point toward a proinflammatory and pro-thrombotic phenotype in response to nocturnal train noise and provide a molecular basis to explain the increased cardiovascular risk observed in epidemiological noise studies

Heart rate, mortality, and the relation with clinical and subclinical cardiovascular diseases: results from the Gutenberg Health Study

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 \u3c 64 subjects was independently associated with increased mortality (Hazard Ratio 1.36; 95% confidence interval 1.06-1.75). This increased risk was also present in HR \u3e 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

Exacerbation of adverse cardiovascular effects of aircraft noise in an animal model of arterial hypertension

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

Quality of life in patients with transcatheter aortic valve implantation: an analysis from the INTERVENT project

BackgroundTranscatheter aortic valve implantation (TAVI) is a standard treatment for patients with aortic valve stenosis due to its very low mortality and complication rates. However, survival and physical integrity are not the only important factors. Quality of life (QoL) improvement is a crucial part in the evaluation of therapy success.MethodsPatients with TAVI were questioned about their QoL before, one month and one year after the intervention as part of the INTERVENT registry trial at Mainz University Medical Center. Three different questionnaires were included in the data collection (Katz ADL, EQ-5D-5l, PHQ-D).ResultsWe included 285 TAVI patients in the analysis (mean age 79.8 years, 59.4% male, mean EuroSCORE II 3.8%). 30-day mortality was 3.6%, complications of any kind occurred in 18.9% of the patients. Main finding was a significant increase in the general state of health measured on the visual analog scale by an average of 4.53 (± 23.58) points (BL to 1-month follow-up, p = 0.009) and by 5.19 (± 23.64) points (BL to 12-month follow-up, p = 0.016). There was also an improvement of depression symptoms, which was reflected in a decrease in the total value of the PHQ-D by 1.67 (± 4.75) points (BL to 12-month follow-up, p = 0.001). The evaluation of the EQ-5D-5l showed a significant improvement in mobility after one month (M = −0.41 (± 1.31), p &lt; 0.001. Regarding the independence of the patients, no significant difference could be found. Apart from that, patients with risk factors, comorbidities or complications also benefited from the intervention despite their poor starting position.ConclusionWe could show an early benefit of QoL in TAVI patients with significant improvement in the subjective state of health and a decrease in symptoms of depression. These findings were consistent over 1 year of follow up

Co-exposure to urban particulate matter and aircraft noise adversely impacts the cerebro-pulmonary-cardiovascular axis in mice

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

Physical Activity in Polluted Air—Net Benefit or Harm to Cardiovascular Health? A Comprehensive Review

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

The COVID-19 pandemic as a starting point to accelerate improvements in health in our cities through better urban and transport planning

[Extract] Cities are arguably the greatest achievement of human civilization. A greater proportion of the global human population is living in cities than ever, and this keeps growing with up to 70% of people expected to live in cities within 20 years. Jobs, wealth and prosperity, innovation, culture, entertainment, and access to healthcare are some of the greatest drivers of the growth and success of cities. But because of their density, cities also tend to be hotspots of air pollution and noise exposure, heat island effects, and more lately the COVID-19 pandemic (Nieuwenhuijsen 2020). Particularly, the more deprived were at higher risk of COVID-19 and already existing inequalities in cities were magnified. Cities also tend to have higher rates of poor mental health, and there were reports of further increases, particular during lockdowns (Kunzler et al. 2021)