Coronary heart disease (CHD) is a chronic heart disease that can cause myocardial ischemia, hypoxia, or necrosis and is usually caused by coronary atherosclerosis. As a typical cardiovascular disease (CVD), CHD is the leading cause of death worldwide (1). The American Heart Association (AHA) suggests that the global number of patients with CHD is likely to double by the year 2030 (2). In terms of prevalence, CHD ranks second among the world's leading causes of death. In China, the disease has been linked to the rising trend of death in the past two decades, from 1980 to 2016, when the average annual growth rate was 9.85%. Based on all these, it is clear that CHD is an important public health issue that negatively impacts people's health and quality of life.

Over the past two decades, a lot of research has profiled arterial hypertension, dyslipidemia, and smoking as risk factors associated with the increased incidence of CHD and related mortality (3). Lifestyle and diet patterns, as common influencing factors of chronic diseases, are related to the risk of CHD. In addition, temperature, relative humidity, barometric pressure, other meteorological factors, and air pollutants are also related to the risk of CHD (4–6). It is important to note that air pollution is harmful to human health in many ways. A growing number of studies have demonstrated that short-term exposure to air pollutants can cause acute and habitual damage to the CV and respiratory and immune systems (7–9). Complex components among air pollutants can induce systemic inflammation and disturb the balance of oxidative stress and the autonomic nervous system. This may cause injury to the CV system and promote the development of atherosclerosis (10, 11), eventually causing the onset and progression of CHD or stroke.

To date, a growing number of studies have shown that short-term exposure to air pollution is related to the rate of CHD (12–15). Nevertheless, most of these studies were conducted in developed countries, where climate conditions and the level of air pollution differ, in many aspects, from those in developing countries. First, comparative studies on climate characteristics and terrain conditions show that prevention and control of air pollution are more difficult in developing countries than in developed countries such as the United States and other European countries. Influenced by the topography of the Qinghai-Tibet Plateau, the Eastern part of China has a significant downdraft in winter, and the atmospheric stratification becomes more stable with less precipitation, which is not conducive to the diffusion of pollutants and wet removal. Second, global warming causes an interdecadal weakening of the East Asian winter monsoon. The average surface wind speed decreases, which is more conducive to the accumulation of pollutants. More importantly, meteorological conditions affect the transmission and diffusion of pollutants, chemical transformation, dry and wet deposition, and other processes. Even within the same country, differences in climate type and geographical location may also lead to differences in the role of atmospheric pollutants. Regardless of these, previous studies carried out in China have mainly reported on the association between PM and hospitalization of CHD (16–18), ignoring research on other pollutants. Therefore, in the present study, we carried out a time-series analysis to explore the relationship between air pollutants and CHD hospitalization in Hefei, and to identify the possible vulnerable sub-populations and meteorological factors. In addition, we employed the DLNM model, which is a modeling framework to flexibly estimate an exposure–time–response function. This modeling framework considers both the lagged effect of exposure factors and the exposure–response non-linear relationship.

Coronary heart disease (CHD) is a major chronic disease that threatens human health and negatively affects patients' quality of life globally. In severe cases of the disease, heart failure, myocardial infarction, and other adverse consequences may occur. More than 40% of deaths in China can be attributed to CHD (24). This implies that the potential contribution of air pollutants to the burden of CHD is significant in China. Nonetheless, the exact mechanism of air pollutants and CV systems remains inconclusive and inadequate. Previously, studies have reported the potential for air pollutants to affect the CV system directly or indirectly. The action mechanisms of air pollution may include epigenetic changes, inflammatory reactions, and other mechanisms, which can stimulate a series of pathological processes such as endothelial damage, vascular dysfunction, autonomic and neuroendocrine dysfunction, thrombosis, and atherosclerosis (25, 26). Exposure to air pollutants may worsen heart failure and reduce heart rate variability in the elderly due to decreased circulatory function and immunity (27).

With the accelerating process of industrialization and urbanization, air pollution has become a big threat to people's health, particularly in densely populated cities. In this study, we investigated the association between air pollutants and CHD hospitalization. The study's findings indicated that exposure to high concentrations of NO₂ and CO correlated with an increased rate of CHD hospitalization. Furthermore, the findings revealed that exposure to O₃ correlated with a lower rate of CHD hospitalization. Sensitivity analysis demonstrated that the model suited well and the outcomes were robust.

The current research found that exposure to NO₂ increases the rate of CHD hospitalization. These findings are supported by previous epidemiological results (28–30). The NO₂ is an index of traffic mixtures, such as ultrafine particles and diesel exhaust black carbon. Previously, studies involving experimental models have demonstrated the potential of diesel exhaust and ultrafine particles to cause noxious biological reactions (31). Thus, NO₂ may promote the development of CHD via mechanisms such as the induction of inflammation and oxidative stress, coronary endothelial vasoconstriction, abnormal regulation of the cardiac autonomic nervous system, increased blood viscosity, and vasospasm. These may eventually contribute to plaque rupture, ischemia, and arrhythmias in CHD hospitalization (32, 33).

The present study revealed that O₃ was negatively correlated with the rate of CHD hospitalization, which may be related to the newly discovered effects of O₃. Studies have shown that O₃ has effective antibacterial and antioxidant defense abilities (34) and is also related to the regulation of immune responses and accelerated wound healing (35, 36). Animal research has shown that O₃ exposure can increase serum concentrations of cholesterol, triglycerides, and low-density (LDL) and very low-density (VLDL) lipoproteins. The risk of CHD increases with an increase in levels of lipid and lipoprotein concentrations in the human body, which is contrary to our findings. It is important to note that O₃ is very active chemically and it can react with other air pollutants to form new compounds (37), making it unstable in the environment. Accordingly, we should be cautious in explaining the effects of O₃ exposure. The mechanism of O₃ in CHD remains to be further studied.

We revealed that CO exposure was related to an elevated rate of CHD hospitalization, which is consistent with previous epidemiological findings (38). Inhaled CO can combine with hemoglobin and form carboxyhemoglobin, thereby reducing the oxygen-carrying capacity of hemoglobin and leading to cellular hypoxia (39). Several possible biological mechanisms have been proposed that underlie the associations between low ambient CO concentrations and CVD. They include cardiac dysfunction (40), systemic inflammation (41), oxidative stress, and thrombotic reactions (42). Both animal models and population-based cohort studies confirm the cardiotoxicity of CO (40, 41). It has been proven that the cardiotoxicity of CO is caused by the dual effects of tissue hypoxia and direct effects on the myocardium. Chen et al. (42) carried out longitudinal research where they investigated 61 patients with CVD. The authors observed that the high-sensitivity c-reactive protein was elevated with short-term exposure to CO. They further reported that Fibrinogen and D-dimer were increased in response to environmental CO exposure. These biomarkers have been associated with thrombotic responses (43). Overall, the above evidence and our outcomes support a correlation between environmental CO exposure and CHD hospitalization risk.

To elucidate the correlation between the four aforementioned air pollutants and the rate of CHD hospitalization, further subgroup analyses regarding varied age, sex, and season groups were conducted. The results showed a correlation between NO₂ exposure and an elevated CHD hospitalization rate in young, female patients with CHD during the hot season. This may be because NO₂ pollution mainly comes from car exhaust. Young people can stay in such an environment longer than the elderly because they engage in more outdoor activities. Women's immunity is weaker than that of men, and the reason that the effect is greater in hot seasons may be that the rise in temperature accelerates the spread of NO₂ in the air and reacts with other pollutants. However, the association between O₃ and CHD hospitalization was more obvious in female patients, patients aged over 65 years, and during the cold season. These findings may be attributed to the fact that women and the elderly are more sensitive to the external environment. Moreover, the photoreaction rate is relatively high in the summer, and the second-generation concentration of O₃ is higher than that in the winter. In terms of CO, it was revealed that CO exposure and CHD hospitalization was more common among patients aged above 65 years. This result implies that age-related serious brain systemic inflammatory environment and lower cerebrovascular hemodynamics might cause CHD cases among the elderly who are more sensitive to the mediators of CO.

Noteworthy, the current study is not without shortcomings. First, we did not consider the spatial heterogeneity of urban air pollution and we calculated the average value of 10 fixed sites by considering the exposure index of NO₂, O₃, and CO. Anyway, almost all the families of hospitalized patients with CHD are within the detection range of urban monitoring stations, which avoids significant spatial differences to some extent. Second, the time-series study methodology is naturally an ecological design, which may be vulnerable to ecological fallacies. Third, the lack of detailed individual information for patients with CHD, such as exercise, mental and mental stress, smoking, and heavy drinking, may have limited subgroup analyses. Fourth, we, unfortunately, failed to obtain specific individual diagnostic data to distinguish between first CHD outpatient visits and recurrent CHD outpatient visits, thus restricting the potential clinical impact of the study results. Finally, this is a single city study. Because of geographical and climatic divergence, the results need to be further verified when extrapolated to other regions.

Despite the shortcomings, our study also has some advantages. Since previous studies have focused more on the health effects of particulate matter on CHD, we have investigated the meteorological factors of NO₂, CO, and O₃ on the risk of CHD hospitalization. In addition, we have identified that the correlation between air pollution exposure and hospitalization risk of CHD may be influenced by season, gender, and age. This information may form a basis upon which healthcare practitioners may formulate novel protective measures to minimize the adverse health effects of air pollution on CHD risk earlier.

Overall, this time-series study shows that short-term exposures to NO₂ and CO positively correlate with the risk of CHD hospitalization. However, O₃ exposure is related to a decreased risk of CHD. Pollutant effects are different in different populations, according to stratified analysis. Consequently, to effectively reduce the risk of CHD admission, it is essential to construct a sound environmental monitoring and feedback system. For susceptible populations, appropriate preventive measures should be developed to avoid unnecessary and harmful exposure.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

Y-TF: conceptualization, methodology, and software. C-FL: data curation and writing—original draft preparation. MH, YF, Y-SH, and YC: writing—reviewing and editing. CC: visualization and investigation. YF, R-DZ, and XF: supervision. L-QJ: software and validation. All authors contributed to the article and approved the submitted version.