Association between PM constituents and cardiometabolic risk factors: Exploring individual and combined effects, and mediating inflammation.

Background: The individual and combined effects of PM constituents on cardiometabolic risk factors are sparsely investigated. Besides, the key cardiometabolic risk factor that PM constituents targeted and the biological mechanisms remain unclear.

Method: A multistage, stratified cluster sampling survey was conducted in two typically air-polluted Chinese cities. The PM and its constituents including sulfate, nitrate, ammonium, organic matter, and black carbon were predicted using a machine learning model. Twenty biomarkers in three category were simultaneously adopted as cardiometabolic risk factors. We explored the individual and mixture association of long-term PM constituents with these markers using generalized additive model and quantile-based g-computation, respectively. To minimize potential confounding effects, we accounted for covariates including demographic, lifestyle, meteorological, temporal trends, and disease-related information. We further used ROC curve and mediation analysis to identify the key subclinical indicators and explore whether inflammatory mediators mediate such association, respectively.

Result: PM constituents was positively correlated with HOMA-B, TC, TG, LDL-C and LCI, and negatively correlated with PP and RC. Further, PM constituent mixture was positive associated with DBP, MAP, HbA1c, HOMA-B, AC, CRI-1 and CRI-2, and negative associated with PP and HDL-C. The ROC analysis further reveals that multiple cardiometabolic risk factors can collectively discriminate exposure to PM constituents (AUC>0.9), among which PP and CRI-2 as individual indicators exhibit better identifiable performance for nitrate and ammonium (AUC>0.75). We also found that multiple blood lipid indicators may be affected by PM and its constituents, possibly mediated through complement C3 or hsCRP.

Conclusion: Our study suggested associations of individual and combined PM constituents exposure with cardiometabolic risk factors. PP and CRI-2 were the targeted markers of long-term exposure to nitrate and ammonium. Inflammation may serve as a mediating factor between PM constituents and dyslipidemia, which enhance current understanding of potential pathways for PM-induced preclinical cardiovascular responses.