Abstract

Background/Aim Evidence demonstrates that coronary artery calcification (CAC) is a biological marker for cardiovascular disease (CVD) risk prediction. Acute cardiovascular effects of temporary and chronic environmental particle exposures sensitive to ≤2.5 micrometers in diameter (here termed “PM2.5”) have been well-studied. However, there is less information on the long-term effects of PM2.5 exposures on the earlier pre-clinical stage of CVD, especially in women (in whom it is also established experience frequent cardiovascular late- and under-diagnoses). This phase of pre-diagnosis pathological activity is classified as subclinical atherosclerosis (SCA) unless and until a patient meets established clinical diagnostic criteria. In this systematic review, we summarize reported associations of long-term PM2.5 and SCA exposure, with investigators placing an emphasis on gender differences in any documented associations. Methods We conducted a comprehensive literature review for articles published from 2007 to 2022 that reported associations of long-term PM2.5 and SCA and evaluated each study with areas of particular focus including study designs, populations at risk, and exposure measures. Results Investigations representing four cohorts yielded equivocal findings related to long-term PM2.5 exposure and CAC. Three cohorts reported positive associations between long-term PM2.5 and CAC development/progression. Two studies supported a strongly positive associations among women or postmenopausal women for PM2.5 on CAC. Studies, however, evaluating PM2.5 exposure associations with carotid intima-media thickness (another biomarker of SCA), reflect increases in both men and women with ↑ PM2.5 levels but reporting no gender differences in PM2.5 exposure and this measure of SCA. Conclusion Our study identifies important gaps in current knowledge synthesis including different methods of PM2.5 estimation and linkage, a lack of consensus of what constitutes long-term air pollution, and the selection of important covariates and intermediate variables. Our aim is to outline best practices going forward in the investigation of PM2.5 long-term exposure and SCA in women

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