If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
University Medical Center Mainz, Department of Cardiovascular Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Tel.: +496131177250, Fax.:+49 6131 17 6615,
University Medical Center Mainz, Department of Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz
University Medical Center Mainz, Department of Cardiovascular Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz
University Medical Center Mainz, Department of Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz
University Medical Center Mainz, Department of Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz
The WHO reports that more than 1.6 million healthy life-years are lost yearly from traffic-related noise in Western Europe. In addition, the number of studies reporting health side effects in response to traffic noise is steadily growing, mainly cardiovascular disease (CVD), such as acute and chronic ischemic heart disease, heart failure, arrhythmia, and stroke. Pathophysiologically nighttime noise has been shown to cause sleep disturbances, including too short sleep periods and frequent interruption of sleep leading to an increase in the levels of circulating stress hormones and subsequently to a significant increase in the production of reactive oxygen species (ROS; =oxidative stress) and inflammation in the vasculature and the brain. The consequence is arterial hypertension and vascular (endothelial) dysfunction, which may increase the risk of cardiovascular disease. With the present review, we will give an overview of the “so-called” non-auditory cardiovascular health effects of noise, which have been proposed to be responsible for the future development of CVD. We will present epidemiological evidence but also evidence provided by translational human and experimental noise studies. Finally, we will discuss maneuvers to mitigate noise effectively.
Among environmental stressors, the health side effects of air pollution on cardiovascular disease (CVD) have been studied extensively. There are close associations between air pollution and CVD, including acute myocardial infarction, heart failure, arrhythmia, hypertension, and stroke (for review, see
). The particulate matter with a diameter of 2.5μm (PM2.5) has been recently demonstrated to be responsible for an excess mortality of about 8.8 million deaths/y
. Further analysis revealed that non-communicable diseases such as cardiovascular disease (ischemic heart disease (40%) and stroke (8%)) as well as other non-communicable diseases, including hypertension and diabetes, are mainly responsible for the excess mortality
. In addition, the European Environment Agency (EEA) has stated in their report 2020 that the number of people exposed to high levels of road traffic noise remains high and will likely increase in the future
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. In Europe, it is estimated that at least 20% of the EU population lives in urban settings where traffic noise levels harm health. They also mention this number is likely to be underestimated
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. Specifically, an estimated 113 million people are affected by long-term day-evening-night traffic noise levels (Lden, indicator of noise exposure that accounts for long-term noise exposure, based on noise levels over a whole day (24 hours), with penalties for nighttime (from 23.00 to 7.00 hours) and evening (from 19.00 to 23.00 hours) noise levels) of at least 55 dB(A). In addition, 22 million are exposed to high levels of railway noise, and 4 million to high levels of aircraft noise
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. There is a clear projection that the number of people exposed e.g., to road noise > 55 dB(A) will increase by 7.8% and to railway noise by 11.8% inside urban areas and by 16.4 and 8.7%, respectively, outside urban areas until the year 2030. In contrast, the number of people exposed to industrial noise will be strikingly reduced by almost 40% inside urban areas while the number of people exposed to aircraft noise inside or outside metropolitan areas will remain unchanged
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. 22 million adults living in Europe in agglomerations or near primary noise sources with levels starting at 55 dB(A) Lden are highly annoyed by noise from road traffic, railways, aircraft and industry
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. Moreover, it is estimated that 6.5 million adults suffer severe sleep disturbance because of nighttime noise levels equal to or above 50 dB(A) Lnight5. Sleep disturbance is a significant risk factor for future cardiovascular events
. The exposure to environmental noise from road traffic, railways, aircraft, and industry are estimated to contribute every year to about 48,000 new cases of ischemic heart disease and 12,000 premature deaths
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
. Thus, even though a huge number of the general population is exposed to transportation noise levels exceeding the recommended guideline noise substantially, transportation noise is not addressed in the AHA/ACC guidelines for prevention
2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.
This review will mainly discuss transportation noise's indirect, non-auditory cardiovascular health effects. This will include the epidemiology of noise and cardiovascular disease as well as the pathophysiology. We will also get insight into the interaction of traditional cardiovascular risk factors such as diabetes, hypertension, hypercholesterolemia, and smoking, and the new environmental stressor noise, which shares many signaling pathways with the classical risk factors
The pathophysiology will focus mainly on the effects of the noise stressor on vascular and cerebral function on endothelial dysfunction, inflammation, oxidative stress, and metabolic disease and will also discuss the impact of effective mitigation maneuvers on cardiovascular side effects.
How does noise cause CVD? The noise reaction model
According to the stress noise concept of Wolfgang Babisch
, there are two pathways in response to noise exposure, the so-called direct pathway, which means that very high decibel levels (higher than 100 dB(A)) will cause damage to the ear organ directly or the so-called indirect pathway which means that lower decibel levels in the range between 50 and 60 dB(A) will disturb activities, sleep, and communication which in turn will result in emotional stress responses such as annoyance or even anger characterized by increased levels of cortisone or activation of the sympathetic nervous system (Figure 1). Chronic stress response will promote the formation of cardiovascular risk factors such as hypertension, increased glucose and cholesterol levels, or an increase in blood viscosity or activation of the coagulation system. Stress responses over the years will lead at the end to cardiovascular disease, including manifest hypertension, atherosclerosis including acute and chronic coronary syndromes, stroke, heart failure and arrhythmia
Figure 1Stress signaling by noise.(A) Noise–stress concept and the adverse health consequences in humans. Noise reaction model for the direct (auditory) and indirect (non-auditory) effects of noise exposure. Panel a reprinted with permission from
. Noise triggers signaling via the hypothalamic–pituitary–adrenal axis (HPA) and sympathetic nervous system (SNS). In the HPA axis, the hypothalamus releases corticotropin-releasing hormone (CRH) into the pituitary gland, which stimulates the release of adrenocorticotropic hormone (ACTH) into the blood. ACTH in turn stimulates the adrenal cortex to produce glucocorticoids and the activation of the SNS leading to the release of catecholamines by the adrenal medulla. Glucocorticoids and catecholamines activate other neurohormonal pathways (such as the renin–angiotensin–aldosterone (RAAS) system), which causes inflammation and oxidative stress with adverse effects on cardiovascular function and molecular targets. Panel b was reprinted with permission from
There is a growing body of evidence that not sleeping long enough is linked to poor health outcomes. This includes a higher prevalence of cardiovascular risk factors like obesity, diabetes mellitus, and high blood pressure and an increased risk of cardiovascular events
. Polysomnographic investigations studying the side effects of acute noise clearly demonstrated an increased likelihood for awakening reactions in response to night-time noise
Prospective cohort studies addressing road noise and sleep have since been published; a study of register information on redemption of sleeping medication showing a weak association with night-time noise >55 dB(A)
The quality of evidence has increased only slightly since the WHO report and noise guidelines for the European region, and more studies using objective or standardized subjective indicators of sleep are needed.
Noise and Arterial Hypertension:
Since noise causes mental stress reactions, the effects of noise on blood pressure have been studied very frequently. Interestingly, the WHO revealed by including more than 35 cross-sectional studies an increased risk of prevalent hypertension of 1.05 (95% confidence interval (CI): 1.02-1.08) for road traffic noise.
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE).
so that evidence supporting an association between traffic noise exposure and hypertension is considered “very low” by the WHO expert panel, indicating that any estimate of effect is very uncertain
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
The association between noise and hypertension appears stronger concerning nighttime versus daytime noise. The HYENA study established a significant association between nighttime aircraft noise and prevalent hypertension. In contrast, no association was seen for daytime aircraft noise, which is in line with nighttime noise events affecting arterial stiffness
Exposure to Road, Railway, and Aircraft Noise and Arterial Stiffness in the SAPALDIA Study: Annual Average Noise Levels and Temporal Noise Characteristics.
Since the publication of the WHO reports inconsistency concerning the effects of noise on blood pressure, reliable conclusions are difficult to make, also warranting more high-quality studies.
Diabetes mellitus and noise pollution:
Transportation noise also has been suggested to be associated with diabetes mellitus
. As discussed, psychological stress caused by noise disturbs the hypothalamic–pituitary–adrenal (HPA) axis leading to an increased release of the stress hormone cortisol, all of which may initiate metabolic disease
, which causes low-grade inflammation, reduces insulin sensitivity, and impairs glucose regulation but may also lead to a dysregulation of appetite-regulating hormones (one causal factor of obesity), all of which are linked to the metabolic disease diabetes mellitus type 2 (T2DM)
. Noise annoyance has also been identified to represent a behavioral pathway through which noise may induce cardiometabolic disease, including diabetes
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
, subsequent prospective studies revealed that in particular regarding road noise, the association with T2DM remained significant even after adjustment for air pollution
Clark C, Sbihi H, Tamburic L, Brauer M, Frank LD, Davies HW. Association of long-term exposure to transportation noise and traffic-related air pollution with the incidence of diabetes: a prospective cohort study. Environmental Health Perspectives. 2017;125.
. More recently, we were able to extend the evidence by demonstrating that long-term exposure to road, railway, and potentially aircraft noise was associated with an increased risk of T2DM in a nationwide cohort of Danish adults, even after adjustment for long-term exposure to ambient air pollution
. In a systematic review and meta-analysis, Sakhvidi et al demonstrated that there is a 6% increase in the risk of diabetes associated with a 5 dB(A) increase in noise exposure
. They also elaborated that T2DM was associated mainly with exposure to air and road traffic noise. In addition, a meta-analysis published by Vienneau et al.
reported a relative risk for incident diabetes of 1.20 (95% CI: 0.88-1.63) per 10 dB(A) in response to aircraft noise and 1.11 (CI: 1.08-1.1%) per 10 dB(A) road noise exposure. Liu et al. demonstrated a significant association between transportation noise exposure and T2DM
Dose-response association between transportation noise exposure and type 2 diabetes: A systematic review and meta-analysis of prospective cohort studies.
Based on the current literature, we propose that diabetes should be considered when estimating the burden of cardiometabolic disease in response to traffic noise exposure.
Noise pollution and annoyance:
Noise annoyance is already the result of stress responses because noise disturbs sleep, communication, and activities
Acute Exposure to Simulated Nocturnal Train Noise Leads to Impaired Sleep Quality and Endothelial Dysfunction in Young Healthy Men and Women: A Sex-Specific Analysis.
provided a novel neurobiological mechanism linking transportation noise with cardiovascular disease. The authors established that in 498 subjects without CVD, amygdala activity, which is part of the limbic system responsible for fight or flight reactions and emotions, was quantified in response to road and aircraft noise. 18F-fluorodeoxyglucose PET-CT investigations revealed that in subjects with high noise exposure, there was within 5y follow-up period evidence of vascular inflammation (aorta). In contrast, in subjects with low noise exposure, amygdala activity was regular and no evidence of vascular inflammation was observed
. In addition, within 5y, high noise exposure was associated with a higher frequency of major adverse cardiovascular events (MACE), including CVD death, myocardial infarction, unstable angina, and cerebrovascular incidents.
Further, mediation analysis revealed that the sequence of events is: noise exposure -> amygdala activation -> sympathetic nervous system and HPA axis activation -> systemic and vascular inflammation ->atherosclerosis -> increased MACE
The evidence base for an association between road traffic noise and obesity has increased markedly since the WHO evaluation, where only 3 cross-sectional studies were available, resulting previously in conclusion: “very low-quality evidence”.
Online-Link3. WHO report "noise and health". http://www.euro.who.int/en/health-topics/environment-and-health/noise/publications/2018/environmental-noise-guidelines-for-the-european-region-2018.
Although markers of obesity vary between the studies, the general picture is that road traffic noise is associated with adiposity markers and obesity. Nevertheless, more studies on the effects of railway and aircraft noise effects on obesity must be conducted, mainly because of the inconsistency of the previous study results.
Recent studies have indicated that exposure to noise may result in unhealthy lifestyle and behavior. Two studies on road traffic noise and physical activity found noise associated with reduced physical activity.
Interestingly, the studies indicated that noise mainly affected whether the subjects participated in leisure time sports at all and not the actual time per week invested in physical activities. Furthermore, one study on smoking and alcohol found road traffic noise positively associated with alcohol consumption and smoking in a cross-sectional design but not in longitudinal analyses.
Therefore, there is still low-quality evidence for an association between noise and lifestyle risk factors, and more studies are warranted to test the hypothesis that transportation noise, through its effect on stress, annoyance, anxiety, and sleep disturbance, leads to an unhealthy lifestyle.
Noise pollution, depression, anxiety disorders, and dementia:
A link between transportation noise and depression has been suggested, but the WHO expert panel concluded that the quality of evidence was rated very low.
WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Quality of Life, Wellbeing and Mental Health.
and an update from 2020 concluded that the evidence increased to “low quality” for road traffic noise, primarily based on an increased risk of antidepressants use and interview measures of depression.
Evidence for Environmental Noise Effects on Health for the United Kingdom Policy Context: A Systematic Review of the Effects of Environmental Noise on Mental Health, Wellbeing, Quality of Life, Cancer, Dementia, Birth, Reproductive Outcomes, and Cognition.
A central problem in studies on depression is that these studies apply a broad range of depression definitions and assessments, ranging from interview measures, intake of antidepressants, and hospital admissions to self-reported depression, making comparing studies difficult. Therefore, more longitudinal studies investigating standardized definitions of depression are needed. Significantly, depression is associated with a higher risk of cardiovascular disease, making depression itself a cardiovascular risk factor
. There is growing evidence that noise causes sleep disturbances leading to cerebral inflammation, oxidative stress, endothelial dysfunction, astrocyte dysfunction, and alterations of the immune system, all of which have been proposed to also cause dementia and Alzheimer's disease
Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline.
. Indeed, experimental studies demonstrated aircraft noise-induced cerebral oxidative stress, neuroinflammation, endothelial dysfunction, and astrocyte and microglia activation in mice within 1-4d of continuous exposure
. The impact of transportation noise on dementia was recently investigated in a population-based study where 103,500 participants with incident dementia were included, 31,219 having a diagnosis of Alzheimer’s disease and 8,664 with vascular dementia, and 2,192 with Parkinson’s disease-related dementia. The authors established that 10y mean exposure to road traffic and railway noise at the most (Ldenmax) and least (Ldenmin) is associated with a higher risk of all-cause dementia and dementia subtypes, especially Alzheimer’s disease
According to the WHO report and noise guidelines for the European region 2018 (which includes studies being published until the end of 2014), there was a significant association between road, aircraft, and railway noise and ischemic heart disease. However, the quality of level of evidence has been rated most as low and very low respectively. This is likely because the noise models employed in these studies were primarily not based on the gold standard for assessing noise exposure, which is based on the levels at the most exposed building facades at the addresses of study participants. Many older studies used the not-very precise postal codes and therefore estimated only the degree of noise occurring at the center of the area or even just using noise maps without having any information about the true noise levels. Thus, the use of noise maps to represent residential exposure may underestimate noise-induced health effects, for small-scale heterogeneously distributed road traffic noise in urban settings
The most significant association was established between road traffic noise and the incidence of ischemic heart disease (RR of 1.08 (95% CI: 1.01–1.15) per 10 dB(A) (Lden)). The quality of the evidence from these longitudinal studies was rated as high
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
(Figure 2). Since that, for aircraft noise, several noise studies reported a significant association between noise and cardiovascular disease and even acute mortality. Saucy et al reported
that in 24,886 cases of death from cardiovascular disease (CVD) from the Swiss National Cohort around Zurich Airport between 2000 and 2015, for nighttime deaths, noise exposure levels 2h preceding death were significantly associated with mortality for all causes of CVD for the highest exposure group (LAeq > 50 dB(A) vs. <20 dB(A))]. Most consistent associations were observed for ischemic heart diseases, myocardial infarction, heart failure, and arrhythmia. Associations were more pronounced for females and for people living in areas with low road and railway background noise and in buildings constructed before 1970. The authors calculated a population-attributable fraction of 3% in their study population and concluded that nighttime aircraft noise can trigger acute cardiovascular mortality
Vienneau et al. reported associations (hazard ratio; 95%-CIs) for road traffic, railway and aircraft noise, and CVD mortality that was 1.029 (1.024–1.034), 1.013 (1.010–1.017), and 1.003 (0.996–1.010) per 10 dB(A) Lden, respectively. Associations for MI mortality were also significant. Blood pressure-related, ischemic heart disease, and all stroke mortality were significantly associated with road traffic and railway noise
. Epigenetic side effects of noise and air pollution were reported in the SAPALDIA study. Eze et al. demonstrated a mutually independent DNA methylation associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses
The WHO guidelines did not evaluate heart failure and atrial fibrillation, two major cardiovascular outcomes. Effects of transportation noise on risk for heart failure have been investigated in five longitudinal studies: two classical cohorts and three population-based studies from London, Switzerland, and the Rhine-Main region. These studies consistently report an association between road traffic, railway, and aircraft noise and heart failure incidence and mortality ranging from 2-8% increase in risk/10dB(A).21, 73-76 Effects of noise on atrial fibrillation have only been examined in a few studies, with some indicating a positive association. In contrast, others report null results,19, 21, 77 stressing the need for more studies on noise in relation to this highly frequent CVD.
Noise and stroke
For stroke, the WHO expert panel ranked the quality of evidence as moderate.
This evaluation was based on five prospective studies: one study on incidence, which found road traffic noise to increase the risk for stroke, and four studies on cerebrovascular mortality, reporting no association.
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
Subsequently, four studies on transportation noise and incident stroke have been published: two extensive population-based studies covering a whole city/region (London and Frankfurt) found road traffic noise to increase stroke risk,
whereas smaller classical cohort studies from Sweden, Norway, and UK with a smaller number of cases (900-1900) but a more comprehensive adjustment strategy found no association.
Two large population-based studies from London and Switzerland have furthermore suggested that road traffic noise and, potentially, aircraft noise may increase the risk for stroke mortality, especially ischemic stroke.
Therefore, although significant, well-designed prospective studies have added to the evidence base, more longitudinal studies are still needed to clarify to what extent transportation noise affects the risk for stroke and whether noise primarily affects the risk of ischemic stroke.
Noise causes endothelial dysfunction: Translational studies in humans
Endothelial function can be considered as a biomarker for subclinical atherosclerosis. It is usually established in subjects with cardiovascular risk factors such as arterial hypertension, diabetes mellitus, hypercholesterolemia and chronic smokers, and oxidative stress
. The generation of increased stress hormone levels, e.g. by noise (Figure 1), is in general accompanied by signs of increased production of vascular reactive oxygen species (ROS = oxidative stress) as well as increased inflammation characterized by increased levels of infiltrated macrophages and cytokines such as IL-6 10. Increased oxidative stress will generally lead to endothelial dysfunction because of the increased degradation of the most critical endothelial signaling molecule, nitric oxide. NO will react with the ROS species superoxide (O2.-) to produce in a diffusion-limited manner the highly reactive intermediate peroxynitrite (ONOO-), which in turn will cause tyrosine nitration of the prostacyclin synthase, thus inhibiting the activity of the very important vasodilator enzyme and by directly inhibiting the activity of the NO target guanylyl cyclase via tyrosine nitration and thiol oxidation
. Peroxynitrite will also cause a direct inhibition of the sGC and oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), an essential cofactor of the eNOS, thus causing eNOS uncoupling, meaning that a NO-producing anti-atherosclerotic enzyme is switched to a pro-atherosclerotic superoxide producing enzyme
, strengthening the concept of endothelial dysfunction being a systemic disease predictor. The significant processes leading to endothelial dysfunction and a brief description of the method of flow-mediated dilation (FMD) to assess endothelial function are summarized in Figure 3.
Figure 3Endothelial dysfunction and its measurement. (A) Mechanisms underlying endothelial dysfunction and the functional consequences of decreased vascular bioavailability of nitric oxide (NO.). In the presence of cardiovascular risk factors such as hypertension, diabetes mellitus, smoking, age, menopause, familiar history of cardiovascular disease and hypercholesterolemia, vascular superoxide-producing enzymes such as the vascular NADPH-oxidase, the xanthine oxidase (XO), and an uncoupled endothelial nitric oxide synthase (eNOS) produce large amounts of superoxide (O2.-), which will metabolize NO. The consequences are adhesion and infiltration of the vascular wall with inflammatory cells such as macrophages and neutrophils and subsequent intima proliferation. (B) Determination of endothelial function using the flow-dependent dilation (FMD) technique. FMD was always measured in the early morning and before 10 a.m. by a technician using standardized techniques. Briefly, brachial artery diameter is measured with a linear ultrasound probe at rest (here 4.5mm) and after a 5min occlusion period with a pressure cuff (here 4.9mm). Changes in diameter are given in percent and reflect the endothelial release of vasodilatory substances such as nitric oxide (NO.) in response to reactive hyperemia. Both panels were reused with permission from
To study whether transportation noise may cause endothelial function, we investigated the effects of nighttime aircraft noise on FMD in healthy volunteers. On the noise exposure nights, an originally recorded aircraft noise, recorded as MP3 files, was played back on a standard portable audio system with a fixed speaker position relative to the head of the subject. The playback volume was leveled at each measurement site to guarantee similar sound pressure levels (SPLs) at all study sites. With these studies, we could demonstrate that nighttime aircraft noise exposure (Leq 46.3 dB(A), peak level 60 dB(A) for 1 night) reduced sleep quality, increased stress hormone levels, caused endothelial dysfunction (a subclinical parameter for atherosclerosis) and decreased pulse transit time (indicating sympathetic nervous system (SNS) activation) in healthy volunteers
. In subjects with established coronary artery disease, the adverse effects of nighttime aircraft noise on endothelial dysfunction were even exacerbated, as expected
Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.
. Endothelial dysfunction induced by aircraft and railway noise responded well to the antioxidant vitamin C suggesting increased oxidative stress as the underlying mechanism (Figure 4)
Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.
Figure 4Field studies on noise effects on endothelial function.Effects of simulated nighttime aircraft and railway noise (noise 30/60 reflecting 30 or 60 playback noise events) on endothelial function (as measured by flow-mediated dilation, FMD) of healthy volunteers (adapted from Schmidt and Herzog et al.
Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.
). Nighttime noise for just one night significantly reduced FMD. The administration of the antioxidant vitamin C was associated with improved endothelial function in aircraft and railway noise-induced exposed control subjects, demonstrating a significant role of oxidative stress.
Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.
So far, the mechanistic studies on the effects of noise on vascular function have been rare and mostly as a noise source white noise has been employed in by far too high decibel levels in the range of 100 dB(A). E.g. exposure of rats to white noise for periods of 2 and 4 weeks (100 dB(A), 4 h/d, 6 d/week) caused impaired endothelium-dependent vasodilation of the aorta, higher sensitivity to the vasoconstrictors as well as hypertension.
Rats exposed to white noise levels of ≥100 dB(A) showed more pronounced oxidative DNA damage (detected by the comet assay) in the heart and adrenal gland.
Thus, even though the results were qualitatively similar as compared to our animal studies using aircraft noise, the consideration that white noise has been shown to significantly improve sleep in subjects complaining of difficulty sleeping due to high levels of environmental noise suggests that these noise sources are not comparable at all
To determine whether the frequency of noise events affects vascular and myocardial function, we studied 70 individuals with established cardiovascular disease or increased cardiovascular risk in two aircraft noise scenarios and one control scenario in a prospective, randomized trial
. Polygraphy recordings, echocardiography, and flow-mediated dilation (FMD) were determined for 3 study nights. The noise patterns consisted of 60 (Noise60) and 120 (Noise120) noise events for one night, respectively, but with comparable Leq, corresponding to a mean value of 45 dB(A). The mean value of noise during control nights was 37 dB(A). During the control night, FMD was 10.02 ± 3.75%, compared to 7.27 ± 3.21% for Noise60 and 7.21±3.58% for Noise120
. Sleep quality was impaired after noise exposure in both noise scenario nights. Serial echocardiographic assessment demonstrated an increase in the E/E' ratio, a measure of diastolic function, within the three exposure nights, with a ratio of 6.83 ± 2.26 for the control night, 7.21±2.33 for Noise60 and 7.83±3.07 for Noise120 respectively. Thus, with these studies, we could demonstrate that aircraft noise with similar Leq, but a different number of noise events results in a comparable worsening of vascular function. We could also demonstrate for the first time the adverse effects of nighttime aircraft noise exposure on myocardial function (diastolic dysfunction), which seemed to be stronger with the higher number of noise events
Noise, cardiovascular and cerebral side effects: Mechanistic studies in animals
Noise causes vascular inflammation and oxidative stress
To identify the molecular mechanisms of endothelial dysfunction, we developed a novel animal model to study the cardiovascular and cerebral side effects of transportation noise
. These studies established increased blood pressure, plasma noradrenaline and angiotensin II levels, kidney corticosterone, and endothelial dysfunction. The noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. The noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, vascular nitrotyrosine positive proteins, and of endothelin-1
. Flow cytometry analysis demonstrated an increase in infiltrated natural killer cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4d did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodeling, and cell death
Further studies revealed that adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by a deficiency of the phagocytic nicotinamide adenine dinucleotide phosphate oxidase (Nox2)
. Around-the-clock aircraft noise exposure of the mice caused the most pronounced vascular effects and dysregulation of Foxo3 regulation of the circadian clock, as revealed by next-generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein downregulation, and Nox2 activation
. Next-generation sequencing revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, nighttime aircraft noise increased oxidative stress, and inflammation biomarkers in serum. These findings indicate that aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce nighttime aircraft noise are severely warranted
The sixth sense is involved in noise-induced stress responses and vascular inflammation: evidence for heightened amygdalar activity in response to transport noise in man.
So far, it remains to be established whether e.g., aircraft noise may have additive side effects on the cardiovascular and cerebral systems of animals with pre-established cardiovascular disease. Thus, we studied the effects of angiotensin II infusion for 7d with or without aircraft noise
. Noise or angiotensin-II increased blood pressure caused endothelial dysfunction, oxidative stress, and inflammation in aortic, cardiac, and/or cerebral tissues in single-exposure models. Most of these risk factors in mice subjected to both stressors showed potentiated adverse changes. Mice exposed to both noise and ATII had additively 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 enhanced vascular and cerebral oxidative stress. Exaggerated renal stress response was also observed. Thus, we established additional cardiovascular and cerebral side effects in animals with arterial hypertension exposed to the environmental stressor noise, 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.
Since traffic noise may play an important role in the development and deterioration of ischemic heart disease, we recently determined the mechanisms of cardiovascular dysfunction and inflammation induced by aircraft noise in a mouse model of myocardial infarction (MI) and in humans with incident MI
Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction.
. Mice were exposed to aircraft noise alone (average sound pressure level 72 dB(A); peak level 85 dB(A)) up to 4d, resulting in pro-inflammatory aortic gene expression in the myeloid cell adhesion/diapedesis pathways. Aircraft noise alone promoted adhesion and infiltration of inflammatory myeloid cells in vascular/cardiac tissue, paralleled by an increased percentage of leukocytes with a pro-inflammatory, reactive oxygen species (ROS)-producing phenotype and augmented expression of Nox-2/phospho-NFκB in peripheral blood. Ligation of the left anterior descending artery worsened cardiac function, pronounced cardiac infiltration of CD11b+ myeloid cells and Ly6Chigh monocytes, and induction of interleukin(IL)-6, IL-1®, MCP-1, and Nox-2, being aggravated by noise exposure before MI. MI induced more substantial endothelial dysfunction and more pronounced increases in vascular ROS in animals preconditioned with noise. Participants of the population-based Gutenberg Health Cohort Study (median follow-up:11.4 years) with incident MI revealed elevated CRP at baseline and worse LVEF after MI in case of a history of high noise exposure and subsequent annoyance development. Thus, aircraft noise exposure before MI substantially amplifies subsequent cardiovascular inflammation and aggravates ischemic heart failure, facilitated by pro-inflammatory vascular conditioning. Our translational results suggest that measures to reduce environmental noise exposure will help improve the clinical outcome of subjects with acute MI.
As mentioned, nighttime noise will cause fragmentation of sleep as well as too short sleep, conditions that have been shown to be associated with severe inflammatory conditions, endothelial dysfunction, blood pressure increases, modifications of the structure of the vasculature, vascular senescence, and recruitment of immune cells in mice
. In an experimental animal study, we investigated the effects of noise on the disruption of the circadian clock by employing a next-generation sequencing technique
. A conserved dysregulation of genes of the circadian clock after noise exposure in the aorta and kidney was identified. However, the overall number of significantly regulated genes varied substantially within these organs (Figure 5). We also established a link between Foxo3 expression and Foxo3 activity and important genes of the circadian clock system, which were all up- or downregulated by around-the-clock aircraft noise in a time-dependent fashion. A role for Foxo3 in the circadian clock is in accordance with previous reports demonstrating that circadian clock oscillation is irregular and that the period is variable upon deletion of Foxo3
. A key role of Foxo3 in noise-induced endothelial dysfunction and vascular/cerebral oxidative stress in general, and dysregulated circadian clock, was also supported by the finding that bepridil, a Foxo3 activator reversed side effects in noise-exposed mice.
Figure 5Noise exposure and the circadian clock.Adverse side effects of around-the clock aircraft noise on the circadian clock. Noise (mean sound pressure level 72 dB(A) for 12 h/day for 1, 2 and 4d) lead to a change of gene expression in the aorta, heart, and kidney. Also the expression of circadian clock genes in the aorta and kidney was changed as established by revealed by Illumina RNA sequencing (A,B). FoxO3 has a binding site in BMAL1 and thereby contributes to the regulation of circadian rhythm. The clock core components consist of the positive regulators CLOCK and BMAL that directly control circadian gene expression as well as the negative regulators PER and CRY (C). The circadian clock regulates several essential biological functions such as sleep, body temperature, appetite, cognitive functions via time-dependent hormone release such as cortisol or melatonin (D). Parts A,B were adopted from
Comparative burden of disease studies demonstrates that air pollution is the primary environmental cause of disability-adjusted life years lost (DALYs). Environmental noise is ranked second in terms of DALYs in Europe and the DALYs attributed to noise were more than those attributed to lead, ozone, and dioxins
Importantly, air and noise pollution have many of the same sources, such as heavy industry, aircraft, railways, and road vehicles, leading to a co-exposure to noise and air pollution. Research suggests that the EU's social cost of noise and air pollution, including excess death and disease, could be nearly 1 trillion EUR. The social cost of alcohol in the EU has been estimated at 50-120 billion EUR, and smoking at 544 billion EUR
Science for environment policy: In depth report 13. The link between noise and air pollution and the socioeconomic status https://ec.europa.eu/environment/integration/research/newsalert/pdf/air_noise_pollution_socioeconomic_status_links_IR13_en.pdf.
. There are several transportation noise or air pollution studies where adjustments for air pollution and noise, respectively, were performed. E.g., in the ESCAPE study, Fuks et al. demonstrated that the incidence of self-reported hypertension was positively associated with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI):1.08; 1.37] per 5 μg/m³) and that adjustment for road noise decreased significantly the estimate 18. In the HUNT study, a significant association between long-term exposure to road traffic noise and ambient air pollution with cardiovascular disease biochemical parameters was established 107. Recently, Sørensen et al. investigated from a multi-exposure perspective the effects of co-exposures on the development of type 2 diabetes
. The authors established that air pollution, road traffic noise, and lack of green space were independently associated with a higher risk of type 2 diabetes
More recently we studied the potentially synergistic effects of particulate matter (PM) and noise based on these considerations. To address this topic, we used an exposure system equipped with an aerosol generator and loudspeakers, where mice were acutely exposed for 3 days to ambient PM and/or noise (aircraft landing and take-off events)
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 was even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers, together with RNA sequencing data, indicate that noise mainly affects the brain and PM in the lungs
. The combination of both stressors has additive adverse effects on the cardiovascular system, likely based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. With these studies, we could also demonstrate an additive upregulation of ACE-2 in the lung, providing a potential explanation for the recently reported increased vulnerability to COVID-19 infection in populations living in highly air and noise polluted areas
. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as the aorta and heart by combined noise and PM exposure
Because there are several sources of noise pollution, each source is requiring tailored abatement measures. In general, we have to differentiate between active and passive noise abatement measures
. Passive approaches include structural modifications, e.g., installing soundproof windows or roof and roller blind box insulation. Active aircraft abatement measures, which means a reduction of noise at its source, include the continuous descending approach, flying higher landing steeper or a GPS-guided approach, thus flight paths that avoid overflying of residential areas or the use of newer engines. These night flight bans are highly effective mitigation measures. For railway noise, speed reduction, noise barriers, and implementation of last-generation brake blocks will be the most efficient active measures leading to a noise reduction between 10 and 20 dB(A). Likewise, road noise can be efficiently reduced actively by quiet road surfaces, low noise tires, changing drive style and electric cars, and passively for railway and road noise by better building insulation or the location of bedrooms along the least exposed façade
. Concerning electric cars, we must consider that road traffic noise is generally generated by the close contact between the tires and the road surface, dominating sound at speeds >30–35 km/h. Thus, replacing combustion engine cars with electric cars will induce a minimal noise reduction, approximately 1 dB(A). Comparisons of the (discounted) costs and benefits of road and rail traffic noise abatement measures suggest that the benefits are higher than the costs in all cases. It is also essential to consider that the most cost-effective approach is clearly to use a combination of strategies
. More greenness is known to significantly reduce the adverse health effects of urban heat islands (in response to the build-up of more concrete), such as fewer hospitalizations, less cardiovascular disease, more biodiversity, better sleep, and even a better indoor microbiome
. A recent study with a total of 1.9 million persons included 128,358 cases of T2DM during follow-up and investigated the association of different environmental risk factors with the risk of diabetes. Using single-pollutant models, all investigated air pollutants, noise and lack of green space were associated with a higher risk of diabetes. They even caused a cumulative higher risk when multi-exposure scenarios were used for these risk factors
. LdenMax, LdenMin and the two proxies of green space remained associated with diabetes in two-pollutant models of noise and green space. In conclusion, air pollution, road traffic noise, and lack of green space are obviously independently associated with a higher risk of T2DM, indicating the importance of green space. Importantly, access to more green spaces may also enhance physical, mental, and community health
The present overview shows evidence that transportation noise may represent an important cardiovascular risk factor. Noise causes CVD and cerebral disease in patients and in experimental animals’ endothelial dysfunction, oxidative stress (by activating the phagocytic NADPH oxidase and by causing eNOS uncoupling), inflammation, and a disturbance of the cerebral and vascular circadian rhythm and increased oxidative stress as well as a downregulation/uncoupling of the neuronal nitric oxide synthase. Within the last several years since the publication of the WHO reports, the evidence that noise causes CVD has substantially increased.
One of the challenges in modelling the effect of environmental factors on cardiovascular outcomes, particularly in ecological studies (which have large samples but are not sufficiently detailed regarding exposure), is the fact that we are looking for a small signal in a substantial amount of noise. This may explain why some of the observed effect sizes are low and the evidence for some associations is equivocal. The effect may be substantial and we cannot measure it accurately.
Future studies will reveal whether classical cardiovascular drugs such as angiotensin-converting enzyme inhibitors, angiotensin 1 receptor blockers (AT-II type 1) statins, or antioxidant enzyme mimetics or heart-healthy city design with the implementation of more greenness will be able to mitigate the noise health side effects effectively.
Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data.
Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies.
We gratefully acknowledge financial support in the form of vascular biology research grants from the Foundation Heart of Mainz (to T.M. and A.D.) and from the Boehringer Ingelheim Foundation for the collaborative research group ‘Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications to study the effects of environmental risk factors on vascular function and oxidative stress. T.M. is a principal investigator of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. We also thank M. Neuser (University Medical Center Mainz, Germany) for her expert graphical assistance with the figures.
References
Al-Kindi SG
Brook RD
Biswal S
Rajagopalan S
Environmental determinants of cardiovascular disease: lessons learned from air pollution.
European Environment Agency. Environmental noise in Europe — 2020. https://www.eea.europa.eu/publications/environmental-noise-in-europe (last accessed on 28 December 2020).
2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.
WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary.
Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE).
Exposure to Road, Railway, and Aircraft Noise and Arterial Stiffness in the SAPALDIA Study: Annual Average Noise Levels and Temporal Noise Characteristics.
Clark C, Sbihi H, Tamburic L, Brauer M, Frank LD, Davies HW. Association of long-term exposure to transportation noise and traffic-related air pollution with the incidence of diabetes: a prospective cohort study. Environmental Health Perspectives. 2017;125.
Dose-response association between transportation noise exposure and type 2 diabetes: A systematic review and meta-analysis of prospective cohort studies.
Acute Exposure to Simulated Nocturnal Train Noise Leads to Impaired Sleep Quality and Endothelial Dysfunction in Young Healthy Men and Women: A Sex-Specific Analysis.
Online-Link3. WHO report "noise and health". http://www.euro.who.int/en/health-topics/environment-and-health/noise/publications/2018/environmental-noise-guidelines-for-the-european-region-2018.
WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Quality of Life, Wellbeing and Mental Health.
Evidence for Environmental Noise Effects on Health for the United Kingdom Policy Context: A Systematic Review of the Effects of Environmental Noise on Mental Health, Wellbeing, Quality of Life, Cancer, Dementia, Birth, Reproductive Outcomes, and Cognition.
Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline.
Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data.
Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.
The sixth sense is involved in noise-induced stress responses and vascular inflammation: evidence for heightened amygdalar activity in response to transport noise in man.
Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction.
Science for environment policy: In depth report 13. The link between noise and air pollution and the socioeconomic status https://ec.europa.eu/environment/integration/research/newsalert/pdf/air_noise_pollution_socioeconomic_status_links_IR13_en.pdf.
Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies.
00150-2&id=fx1.jpg){kind=link}
00150-2&id=gr1.jpg){kind=link}
00150-2&id=gr2.jpg){kind=link}
00150-2&id=gr3.jpg){kind=link}
00150-2&id=gr4.jpg){kind=link}
00150-2&id=gr5.jpg){kind=link}