Thrombotic Markers in Metabolic Syndrome Subjects Exposed to Diesel Exhaust

Abstract

Traffic-derived particulate matter (PM) is associated with cardiovascular morbidity and mortality, but the mechanism of this association is unclear. Prothrombotic processes have been linked to PM in epidemiological and animal models, but have not been consistently implicated in controlled human models. Diesel exhaust (DE) is a major contributor to PM. We conducted a controlled human exposure of DE in subjects with metabolic syndrome. The study objective was to evaluate DE exposure effects on prothrombotic markers in a population vulnerable to cardiovascular disease. A randomized, crossover, double-blinded design was used: 16 subjects with metabolic syndrome exposed on 3 different days (≥ 2 wk washout) to DE at 0 (filtered air, FA), 100 μ g PM_2.5/m³ (DE₁₀₀) and 200 μg PM_2.5/m³ (DE₂₀₀). We assessed DE-associated changes in D-dimer, von Willebrand factor (VWF), and plasmin activator inhibitor-1 (PAI-1) at 3, 7, and 22 h after exposure initiation. A DE₂₀₀-attributable decrease (1.17-fold; CI 1.04 to 1.34) in VWF was noted at 7 h. Significant changes did not occur in other primary endpoints. As previously noted with healthy subjects, strong diurnal patterns in PAI-1 were observed. Thus, in a novel study, we were unable to demonstrate a prothrombotic effect of moderate-dose diesel exhaust exposure in a population at risk for cardiovascular disease.

Support for this study was provided by grants R830954 and R827355 from the U.S. Environmental Protection Agency, M01RR-00037 from the National Institutes of Health (University of Washington–General Clinical Research Center), and ES013195, ES011139, and P30ES07033 (University of Washington–Center for Ecogenetics and Environmental Health) from the National Institute for Environmental Health Sciences. We thank Mary Aulet, Timothy Gould, Karen Jansen, Sara Jarvis, Jim Stewart, and the University of Washington's General Clinical Research Center staff for invaluable assistance with the conduct of this study; Anne Ho for assistance with manuscript preparation; Wayne Chandler for reviewing the manuscript; and the study subjects for their willingness to contribute.