Environmental stressors and cardiovascular disease: the evidence is growing

This editorial refers to ‘Long-term exposure to road traffic noise, ambient air pollution, and cardiovascular risk factors in the HUNT and Lifelines cohorts’†, by Y. Cai et al., on page 2290. The Global Burden of Disease Study estimated that the worldwide impact of air pollution [particulate matter (PM)2.5] was as many as 4.2 million deaths and 103 million disability-adjusted life years (DALYs) in 2015.1 Exposure to ozone caused an additional 254 000 deaths and a loss of 4.1 million DALYs from chronic obstructive pulmonary disease in 2015.1 In addition, high acute NO2 exposure levels are associated with a significant increase in cardiovascular mortality.2 Similar to the pervasive influence of air pollution, noise and its ‘so-called’ non-auditory effects are pervasive in the urban environment.3 The non-auditory effects include annoyance, sleep disturbance, and psychological stress, and are widely suspected to cause worldwide disability. According to the World Health Organization (WHO), at least 1 million DALYs are lost every year in western European countries because of environmental noise, and cardiovascular disease (CVD) contributes to the vast majority of these deaths.3 Traffic noise and air pollution have also been associated with increased risk of metabolic syndrome, obesity, and type 2 diabetes.4 , 5 Taken together, there is a growing body of evidence that the environmental exposure to traffic noise and air pollution can cause CVD, including coronary heart disease, myocardial infarction, arterial hypertension, heart failure, arrhythmia, and stroke.4 , 6 In general, studies addressing the effects of the environmental stressors noise and air pollution on traditional biological cardiovascular risk factors are rather limited. With the present study, Cai et al.7 investigated the associations of daytime road traffic noise and air pollution, estimated as PM10 and NO2, in two large European population-based cohorts, from respectively, Norway (HUNT) and the Netherlands (Lifelines), on high sensitivity C-reactive protein (hs-CRP), blood lipids, and glucose levels. After pooling of the cohorts, an interquartile range (IQR) higher noise [5.1 dB(A)] was associated with 1.1% higher hsCRP, 0.7% higher triglycerides, and 0.5% higher HDL; only the association with HDL was robust to adjustment for air pollution. An IQR higher PM10 (2.0 μg/m3) or NO2 (7.4 μg/m3) was associated with higher triglycerides independent of adjustment for noise. Additionally, for NO2, a significant association with hsCRP was established. In Lifelines, an IQR higher noise [4.2 dB(A)] and PM10 (2.4 μg/m3) was associated with 0.2% and 0.6% higher fasting glucose, respectively, both remaining robust to mutual adjustment. The authors concluded that long-term exposures to road traffic noise and ambient air pollution were associated with significant changes in blood biochemistry, providing a possible link between these exposures and the increased cardio-metabolic disease risk observed in epidemiological studies. As commented by the authors, the observed effects of road traffic noise and air pollution on CVD risk factors were small. However, given the high proportion of the population exposed to high levels of these pollutants, the effect of this observation could be that the entire distribution of these risk factors may be shifted towards a less favourable profile at population level, i.e. ‘at-risk’ populations may be increased. Only a limited number of studies have estimated exposure to both air pollution and traffic noise within the same study, and assessed effects of mutual adjustment. These studies mostly suggested that traffic noise and air pollution may independently contribute to the risk of cardiovascular incidence and mortality: a meta-analysis indicated that correction for either air or traffic noise pollution did not change the association of the other with respect to CVD outcome.8 However, some studies have found the association between road traffic noise and CVD to disappear after adjustment for air pollution, and vice versa,9 , 10 and this field clearly needs more research. For diabetes, the very studies including both air pollution and traffic noise indicated that traffic noise may increase risk independently of air pollution, whereas for air pollution the picture was not clear. The present study by Cai et al.,7 which included both exposures, did not clarify this question, as for some biomarkers association with one exposure disappeared after adjustment for the other exposure, whereas for other biomarkers the association was robust to mutual adjustment. This illustrates the complexity of assessing effects of these two pollutants known to be highly correlated in urban environments, and highlights the importance of studies addressing this. Gaining such knowledge is important for planning optimal prevention strategies. There are currently no studies that have simultaneously examined the effects of controlled exposure to traffic noise and air pollution in experimental animal or human studies. A number of important questions at the mechanistic level in animals may help provide direction for future human studies, both experimental and epidemiological. The questions that need to be addressed are many and include assessment of: the magnitude and time course of the response to joint noise and air pollution exposure; interactive effects of both exposures on, for example blood pressure, blood lipids, and measures of metabolic risk; duration of effect and time course of reversal; impact of low-grade background noise on air pollution exposure effects, and vice versa; impact of noise-induced sleep disturbance on effects of air pollution; and finally the effect of prevention and lifestyle (e.g. diet, stress, and exercise). Elucidating whether co-exposure to both noise and air pollution have combined effects on a mechanistic level is important to help us understand the interplay between these highly frequent environmental exposures in relation to human health. Recent translational studies on the effects of traffic noise on vascular function have revealed that noise causes arterial hypertension and increases circulating stress hormones, endothelial dysfunction, oxidative stress (in both the plasma and vasculature), and the sensitivity of the vasculature to vasoconstricting agents.11–13 These characteristics strikingly resemble characteristics observed in response to exposure to particulate matter, in particular with the consequence of increased oxidative stress within the vasculature.13 , 14 Thus, in most circumstances where air pollution and noise plus traditional vascular risk factors coincide, additional vascular damage is to be expected (Figure 1), again highlighting the importance of addressing how these exposures interplay at a mechanistic level. Suggested mechanisms behind adverse effects of noise and air pollution on cardiovascular health. Both air pollution [particulate matter (PM)] and noise may lead to activation of the hypothalamic–pituitary–adrenal (HPA) axis, thereby increasing risk for chronic stress, characterized by increased levels of circulating catecholamines and glucocorticoids.4 , 15 In addition, both environmental stressors may increase other traditional and novel risk factors4 , 15 characterized by changes in blood chemistry including an increase in high sensitivity CRP (hsCRP) and in lipid, glucose, and triglyceride (TG) levels, thereby increasing risk for cardiovascular disease, including coronary artery disease, stroke, heart failure, arterial hypertension, and metabolic disease. For the future, the development of technologies that provide measures of personal environmental exposure in conjunction with measures of health may provide an unprecedented opportunity for research and may allow an extraordinary understanding of the interactions between environmental and health. To conclude, with this new study by Cai et al.,7 the evidence that environmental stressors can cause cardiovascular and metabolic disease is growing, although mechanistic insights into how traffic noise and air pollution interplay are still warranted. We are indebted to Margot Neuser for excellent graphical assistance. Research focusing on environmental stressors is supported by a vascular biology research grant from the Foundation Heart of Mainz research and from the Boehringer Ingelheim Foundation for the collaborative research group; ‘Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications’. T.M. is Principle Investigator of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. Conflict of interest: none declared.