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There has been no investigation to date of adults with metabolic syndrome examining the association of short and long-term exposure to fine particulate matter (PM2.5) air pollution with cardiovascular-disease related inflammatory marker (WBC and CRP) levels in a nationally representative sample. The goal of this study is to assess the susceptibility of adults with metabolic syndrome to PM2.5 exposure as suggested by increased cardiovascular-disease related inflammatory marker levels.A cross sectional analysis of adult National Health and Nutrition Examination Survey (NHANES) participants (2000–2008) was carried out with linkage of CDC WONDER meteorological data and downscaler modeled USEPA air pollution data for census tracts in the continental United States.Participants were non-pregnant NHANES adults (2000–2008) with complete data for evaluating presence of metabolic syndrome and laboratory data on WBC and CRP. Exposures studied included short (lags 0–3 days and their averages), long-term (30 and 60 day moving and annual averages) PM2.5 exposure levels at the census tract level in the continental United States. The main outcomes included CRP and WBC levels the day of NHANES study visit analyzed using multiple linear regression, adjusting for age, gender, race, education, smoking status, history of any cardiovascular disease, maximum apparent temperature and ozone level, for participants with and without metabolic syndrome.A total of 7134 NHANES participants (35% with metabolic syndrome) met the inclusion criteria. After adjusting for confounders, we observed a significant effect of PM2.5 acutely at lag day 0 on CRP level; a 10 μg/m3 rise in lag day 0 PM2.5 level was associated with a 10.1% increase (95% CI: 2.2–18.6%) in CRP levels for participants with metabolic syndrome. For those without metabolic syndrome, the change in CRP was −1.3% (95% CI −8.8%, 6.8%). There were no significant associations for WBC count.In this first national study of the effect of PM2.5 air pollution on levels of cardiovascular-disease related inflammatory markers in adults with metabolic syndrome, CRP levels were found to be significantly increased in those with this condition with increased fine particulate matter levels at lag day 0. With one third of US adults with metabolic syndrome, the health impact of PM2.5 in this sensitive population may be significant.A cross sectional study of the effect of PM2.5 AP on inflammatory biomarkers among NHANES participants was conducted.Participants’ Census tract of residence was linked to USEPA downscaler modeled air pollution for the continental US.Goal was the assessment of susceptibility of adults with metabolic syndrome to PM2.5 exposure and levels of CRP and WBC.There was a significant effect of PM2.5 at lag day 0; a 10 μg/m3 rise was associated with a 10.1% increase in CRP level.There were no significant associations with CRP or WBC for those without metabolic syndrome.