Modifying effect of statin use on the association between nitrogen dioxide exposure and ischemic heart disease in patients with hypertension

Abstract

Background: Air pollution, particularly nitrogen dioxide (NO2), adversely affects cardiovascular health by inducing systemic inflammation. Evidence remains limited regarding short-term exposure to traffic-related air pollution, including NO2, and whether statin use modifies susceptibility to pollution-related acute cardiovascular events. This study evaluated whether the short-term effects of NO2 exposure and ischemic heart disease (IHD) hospitalization differ by statin-use status, focusing on patients with hypertension. Methods: A time-stratified case-crossover analysis was conducted using data from National Health Insurance Service for patients hospitalized with IHD in Seoul from 2018 to 2020. The included patients had a prior diagnosis of hypertension and had used antihypertensive medication within the previous 3 years. This group was further stratified as prescription-based statin users and non-users based on whether they had received a statin prescription within 1 year before their IHD admission. The daily average NO2 concentrations in Seoul were retrieved from Air Korea for the admission day and the preceding 7 days. Weighted conditional logistic regression models were applied separately for each subgroup after adjusting for meteorological conditions and national holidays. The risk of IHD hospitalization was presented as odds ratios (ORs) per 0.01 ppm increase in NO2, with 95% confidence intervals (CIs). Differences in risk between statin users and non-users were tested (Pfor interaction). Results: Of the 72,753 IHD cases analyzed, 24% were statin non-users and 76% were statin users. A 0.01 ppm increase in NO2 at lag0 was associated with higher odds of IHD-related hospitalization (OR, 1.012; 95% CI, 1.003-1.020), with similar results for lag0-lag5 and cumulative windows (lag01, lag02). A significant interaction between NO2 exposure and statin use was identified (P for interaction < 0.05). The associations differed by statin-use status, with generally lower, non-significant estimates among statin users. Among non-users, significant positive associations were observed at lag1, lag2, and lag01(ORs > 1). In contrast, estimates among statin users were lower and non-significant. Conclusions: Short-term NO2 exposure was associated with an increased risk of hospitalization for IHD among patients with hypertension. However, this association differed by statin-use status, with lower estimates observed among statin users than non-users.