Impact of carbon monoxide and nitrogen dioxide on cardiovascular biomarkers in the Study of Women's Health Across the Nation

Abstract

Introduction: Impacts from ambient carbon monoxide (CO) and nitrogen dioxide (NO2) on cardiovascular disease (CVD) has been reported, but the biologic mechanisms connecting them remain uncertain. This study examined whether elevated ambient CO and NO2 levels related to levels of CVD markers in midlife women. Methods: Annual repeated measurements of ten CVD markers, including high-sensitivity C-reactive protein (hs-CRP), fibrinogen, Factor VIIc, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor Type 1 (PAI-1), and lipoprotein markers, were obtained from 2,207 women from five racial/ethnic groups enrolled in 6 US cities for the longitudinal Study of Women’s Health Across the Nation (average 3.8 visits/woman, mean age: 51±3 years). CO and NO2 data were obtained from the USEPA and assigned to each woman based on proximity to her home address. Prior year, 6-month, 30-day, 7-day, and one-day exposures were calculated, and their associations with CVD markers were examined using longitudinal mixed-effects models. Results: Adjusting for site, race/ethnicity, education, menopause status, body mass index, smoking, and recent alcohol use, CO and NO2 exposures were positively associated with fibrinogen, PAI-1, and tPA-ag levels. For an interquartile increase of the 1-year average gas concentration, 0.68 ppm for CO and 13 ppb for NO2, PAI-1 level increased 35% (95% CI: 29%, 42%) and 71% (57%, 86%), respectively. The same increases in the 30-day average CO and NO2 concentration corresponded to 4.5% (2.6%, 6.5%) and 4.5% (2.0%, 7.0%) increases in fibrinogen level. Adjusting for long-term PM2.5 exposure, the impact of 1-year CO exposure on PAI-1 was reduced to 18% (12%, 25%), and the association between CO and tPA-ag was null, indicating that PM2.5 also contributed to variations in these CVD markers. Conclusions: CO and NO2 exposures may increase coagulation and thrombotic potential, and thus may increase risks of CVD in midlife women.