The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and Cardiovascular Risk

Abstract

Epidemiological studies have provided evidence that traffic noise exposure is linked to cardiovascular diseases such as arterial hypertension, myocardial infarction, and stroke. Noise is a nonspecific stressor that activates the autonomous nervous system and endocrine signaling. According to the noise reaction model introduced by Babisch and colleagues, chronic low levels of noise can cause so-called nonauditory effects, such as disturbances of activity, sleep, and communication, which can trigger a number of emotional responses, including annoyance and subsequent stress. Chronic stress in turn is associated with cardiovascular risk factors, comprising increased blood pressure and dyslipidemia, increased blood viscosity and blood glucose, and activation of blood clotting factors, in animal models and humans. Persistent chronic noise exposure increases the risk of cardiometabolic diseases, including arterial hypertension, coronary artery disease, diabetes mellitus type 2, and stroke. Recently, we demonstrated that aircraft noise exposure during nighttime can induce endothelial dysfunction in healthy subjects and is even more pronounced in coronary artery disease patients. Importantly, impaired endothelial function was ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting that excessive production of reactive oxygen species contributes to this phenomenon. More recently, we introduced a novel animal model of aircraft noise exposure characterizing the underlying molecular mechanisms leading to noise-dependent adverse oxidative stress-related effects on the vasculature. With the present review, we want to provide an overview of epidemiological, translational clinical, and preclinical noise research addressing the nonauditory, adverse effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal. 28, 873-908.

Keywords: aircraft noise exposure; endothelial dysfunction; environmental risk factors; oxidative stress; stress hormones; traffic noise exposure.

FIG. 1.

Noise reaction scheme explaining the adverse cardiovascular effects of noise exposure. Adapted from Münzel et al. (162) with permission of the publisher. Copyright © 2014, Oxford University Press.

FIG. 2.

The most important diseases/injuries and risk factors for the global all-cause mortality and life years spent with significant illness and/or disability. DALYs, disability-adjusted life years. Figure was drawn de novo according to data presented by Lim et al. (143) and Murray et al. (168).

FIG. 3.

Noise thresholds and guidelines. Adapted from Münzel et al. (166) with permission of the publisher. Copyright © 2017, Oxford University Press.

FIG. 4.

Title page of the Book from Karl Kryter summarizing the effects of noise on man, discussing man's nonauditory system responses including information about the effects of noise on work performance, sleep, feelings of pain, vision, and blood circulation. Book cover art by Kryter (130). Copyright © 1970 Academic Press, Inc. Published by Elsevier Inc. All rights reserved.

FIG. 5.

Difference in percent of occurrence of physiological problems in 1005 German industrial workers. Figure drawn de novo from data reported in Kryter (131).

FIG. 6.

Exposure–response relationships of the associations between transportation noise and cardiovascular health outcomes. Air, aircraft noise; dB(A), A-weight decibels; CHD, coronary heart disease; Hyp, hypertension; Road, road traffic noise. Adapted from Münzel et al. (166) with permission of the publisher. Copyright © 2017, Oxford University Press.

FIG. 7.

Relationship between environmental noise sources and the degree of annoyance. (A) Degrees of overall annoyance according to different sources of noise. (B) Sources of extreme annoyance. Adapted from Beutel et al. (31) with permission of the publisher/authors. Copyright: © 2016, Beutel et al. (open access).

FIG. 8.

Association between noise annoyance, depression, and anxiety. CI, confidence interval. Adapted from Beutel et al. (31) with permission of the publisher/authors. Copyright: © 2016, Beutel et al. (open access).

FIG. 9.

Kaplan–Meier analysis of event-free survival refers to subgroups of patients categorized as being below and above the median values for mean FMD. Lower FMD was associated with higher cerebro-cardiovascular event incidence. FMD, flow-mediated dilation. Reprinted from Ostad et al. (182). Copyright (2014), with permission from IOS Press. The publication is available at IOS Press through http://dx.doi.org/10.3233/CH-131720

FIG. 10.

Impact of oxidative stress on endothelial function and event-free survival of patients. (A) Maximal ACh-induced vasodilation in patients with and without cardiovascular events during saline and vitamin C infusion. Vitamin C improved ACh-induced vasodilation significantly larger in patients with events compared with patients without events. (B) Kaplan–Meier analysis demonstrating cumulative proportion of patients without cardiovascular events during follow-up. Effect of vitamin C on ACh-induced vasodilation is divided into values below and above the median, p < 0.05 versus group without vitamin C (blue bars). Adapted from Heitzer et al. (106). With permission of Wolters Kluwer Health, Inc. Copyright © 2001, American Heart Association, Inc.

FIG. 11.

Physiology and pathophysiology in the intact and damaged vasculature with direct effects of oxidative stress. NO, nitric oxide; ONOO⁻, peroxynitrite; XO, xanthine oxidase. Modified from Daiber and Münzel (54a). With permission of the publisher. Copyright © 2006, Steinkopff Verlag Darmstadt.

FIG. 12.

Effects of simulated aircraft noise (noise 30 and 60 reflecting 30 or 60 playback aircraft noise events) on endothelial function (as measured by FMD) and (lower right) stress hormone levels of healthy volunteers. The administration of the antioxidant vitamin C (upper right) was associated with improved endothelial function, demonstrating a role of oxidative stress. Adapted from Schmidt et al. (208) with permission of the publisher. Copyright © 2013, Oxford University Press.

FIG. 13.

Impact of noise exposure during the sleep phase on different cardiovascular and hemodynamic parameters. Effects of nighttime aircraft noise on flow-dependent dilation (A), on systolic blood pressure (B) and on sleep quality as expressed by the VAS (A) and data are mean ± SD in 60 patients with established coronary artery disease. Significance levels are *p = 0.001 for (A), *p = 0.03 for (B), and p < 0.001 for (C), respectively, adjusted for gender, age, night sequence, PSQI, overall noise sensitivity (NoiSeQ), sleep-related noise sensitivity, attitude toward aircraft noise, and the results of the Morning Evening Questionnaire. PSQI, Pittsburgh sleep quality index; SD, standard deviation; VAS, visual analog scale. Adapted from Schmidt et al. (207) with permission of the publisher/authors. Copyright: © 2015, Schmidt et al. (open access).

FIG. 14.

Setup of the noise exposure system used for the mouse studies.

FIG. 15.

Selected data of our recently published noise exposure mouse study. Exposure to aircraft noise led to elevated systolic blood pressure (red symbols) (A), impaired endothelial function (B), reduced vascular NO levels [measured with EPR as described (128)] (C), and enhanced sensitivity to vasoconstrictors (D). Exposure to aircraft noise led to increased staining of vascular 3-nitrotyrosine-positive proteins (E, F) and vascular autocrine endothelin-1 production (G, H). The staining reflects representative immunohistochemical images. Brown color indicates 3-nitrotyrosine-positive proteins or endothelin-1 expression and localization. EPR, electron paramagnetic resonance spectroscopy; ET-1, endothelin-1. Modified from Münzel et al. (161) with permission of the publisher/authors. Copyright © 2017, Münzel et al. (open access). Published by Oxford University Press on behalf of the European Society of Cardiology.

FIG. 16.

Postulated mechanisms of noise-induced (cardio)vascular damage are based on the vascular functional and observational parameters as well as results from next-generation sequencing of our recent mouse study on the effects of aircraft noise exposure on the cardiovascular system. eNOS, endothelial nitric oxide synthase; Foxo, Forkhead-box-protein; Ihh, Indian hedgehog; ^•NO, nitric oxide; Nox2, NADPH oxidase isoform 2, ROS, reactive oxygen species, Ypel2, Yipee-like 2.

FIG. 17.

Proposed pathophysiological mechanisms of cardiovascular disease induced by environmental air pollution and noise. 7-KC, 7-ketocholesterol; ox-PAPC, oxidatively modified 1-palmitoyl-2-arachidonoyl-sn-phosphatidylcholine. Adapted from Münzel et al. (166) with permission of the publisher. Copyright © 2016, Oxford University Press.

FIG. 18.

Hypothetical framework of investigations that combine technological innovation in biometric data with personalized exposure information in real time to study interactive effects of environmental risk factors on cardiovascular endpoints. ABP, ambulant blood pressure monitoring; BC, black carbon; PM, particulate matter. Adapted from Münzel et al. (167) with permission of the publisher. Copyright © 2016, Oxford University Press.

FIG. 19.

Overview on human and animal evidence of noise-induced cardiovascular complications. IL-6, interleukin-6; SOD, superoxide dismutase.