In an academic tertiary care center, we investigated 2,337 patients admitted to the ICCU over the course of one year, and found that short-term PM2.5 exposure before ICCU admission was associated with an increased risk of incident major ANCI (especially acute respiratory failure and acute kidney injury), greater acute severity of illnesses, increased need for advanced monitoring and therapeutic devices, as well as worse clinical outcomes. To our knowledge, this is the first study to report the short-term effect of ambient air pollution on patients who need acute cardiac care.
A large number of time-series studies have demonstrated that short-term PM2.5 exposure was associated with increased risk for near-term myocardial infarction, cardiac arrest, and mortality in the general population, although there was heterogeneity in the effect estimates in different studies (6–8). Our data were mostly in agreement with previous studies. We also found that the increased risk of STEMI seemed to be more pronounced than that of other types of ACS, though admission bias could not be excluded as a contributing factor. Possible biological mechanisms contributing to the acute cardiovascular effect of PM2.5 exposure have been well described. Three broad intermediary pathways, including systemic oxidative stress and inflammation, autonomic imbalance favoring sympathetic activation, and potential direct actions of particulate matters reaching the systemic circulation, as well as the subsequent specific biological responses (e.g., endothelial dysfunction, vasoconstriction, plaque vulnerability, decreased heart rate variability, etc.), have been proposed to underlie cardiovascular events following short-term PM2.5 exposure (15, 16). These underlying mechanisms may be primarily responsible for the difference in cardiovascular events in vulnerable ICCU patients exposed to variant PM2.5 levels.
We also found that the incidence of major ANCI was more prevalent in ICCU patients with higher short-term PM2.5 exposure. Thus far, studies about the health effect of ambient fine particulate matter have focused on the general population, while there have been no investigations of this effect in individuals requiring acute cardiac care. Due to the aging population and increasing chronic comorbidities, the vulnerability of these susceptible individuals tends to be more significant than that of the general population (17). Consequently, these patients may suffer a larger clinically meaningful impact of short-term PM2.5 exposure that is not limited to the cardiovascular system. On the other hand, some studies have reported that ANCI is common and associates with increased mortality risk in contemporary ICCU settings (9, 10). In consideration of a possible multisystemic consequence following short-term PM2.5 exposure and the meaningfulness of ANCI, it is crucial to explore whether short-term PM2.5 exposure is associated with the incidence of major ANCI. Our findings confirm the existence of this association.
Previous studies have linked short-term PM2.5 exposure to the increased risk of decreased lung function (18, 19) and acute respiratory failure (20, 21) in apparently healthy individuals. The mechanism suggested to explain this acute health effect is the acute airway response caused by activation of inflammatory pathways and small airway constriction owing to the chemical constituents of inhaled fine particulates (18, 21). For vulnerable ICCU patients, the poorer physiological and pulmonary reserve could result in a more pronounced decrease in lung function following short-term PM2.5 exposure. This in turn may increase the risk of incident acute respiratory failure. Furthermore, some studies found that one-year PM2.5 exposure was associated with lower renal function in the general population (22, 23). Although no human studies have ever investigated whether short-term PM2.5 exposure is linked to the incidence of acute kidney injury, some animal experiments have demonstrated that short-term exposure to fine particulates, urban particulates, or diesel exhaust particulates, could induce inflammation and oxidative stress in peri-renal adipose tissue (24), increase cytokine expression in the kidney (25), and aggravate experimental acute renal failure (26) in rats, respectively. We speculated that there might be certain biomechanisms linking short-term PM2.5 exposure to the increased risk of acute kidney injury because of the marked vulnerability and high PM2.5 exposure of our study population, but further investigations are needed.
Numerous prior studies found that short-term elevated PM2.5 was associated with the risk of infections, especially acute respiratory infection (27, 28). However, the only study that investigated the association of PM2.5 exposure with incident community-acquired sepsis, did not yield statistically significant results (29). The cause for the increase in the number of sepsis cases in higher PM2.5 exposure groups in our study population may be iatrogenic and may be attributed to catheter-related or ventilation-related infections resulting from the more use of advanced hemodynamic monitoring and therapeutic devices due to the more significant acute severity of illnesses. Similarly, studies examining the correlation between short-term PM2.5 exposure and gastrointestinal hemorrhage have also failed to yield positive results (30, 31). However, though one study reported a positive correlation between elevation in nitric oxide and an increased risk of gastrointestinal hemorrhage, the researchers admitted that distinguishing between the individual effects of nitric oxide and PM2.5 was challenging because they were highly correlated (30). Hence, the causes for numerically more episodes of gastrointestinal hemorrhage in patients with higher PM2.5 exposure in our study may represent either an effect of nitric oxide or PM2.5. A greater number of stress ulcers related to the increased acute severity of illnesses may also be a contributing factor.
In brief, short-term PM2.5 exposure may increase the incidence of ANCI, a major risk factor for mortality in ICCU patients (10), and this may be mediated via some biological mechanisms in addition to its cardiovascular effect. On this basis, the complex physiological interactions between the organs or physiological systems (e.g., cardiopulmonary interaction, cardiorenal interaction, etc.) secondary to ANCI and acute cardiovascular diseases may further exacerbate the acute severity of illnesses, increase the need for advanced hemodynamic monitoring and therapeutic devices, and worsen clinical outcomes. Furthermore, the increase in emergency room visits for cardiopulmonary diseases caused by severe air pollution (32) may delay the time of first medical contact and increase the risk of mortality in patients with higher short-term PM2.5 exposure. All of the above may provide an explanation for the association between short-term PM2.5 exposure and the increased need for advanced devices and worse clinical outcomes in our study.
Our study should be interpreted in the context of the following limitations. First, PM2.5 exposure measurement errors were inevitable because we simply averaged monitoring results across various sites as the proxy for actual individual exposure. However, this is an inherent disadvantage of all human studies involving air pollution. Second, potential confounders from other pollutants could not be entirely excluded because they usually correlate highly with PM2.5 concentration, although we found no similar association in the preliminary analysis. Third, the interaction between ambient air pollution and weather conditions was intricate, as in previous studies, the adjustment for meteorological variables in our regression models may not exclude unmeasured cofounders. Finally, samples in this single-center study were subject to geographical restrictions, which affected their representativeness and generalization. Further high-quality multicenter time-series studies are needed to provide more evidence regarding this issue.