title: 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 (> or = 2 wk washout) to DE at 0 (filtered air, FA), 100 microg PM(2.5)/m(3) (DE(100)) and 200 mug PM(2.5)/m(3) (DE(200)). 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 DE(200)-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.
authors.affiliation: Department of Medicine and School of Environmental Health, University of British Columbia, Vancouver, BC, Canada. chris.carlsten@vch.ca
authors.forename: C
authors.initials: C
authors.lastname: Carlsten
authors.forename: J D
authors.initials: JD
authors.lastname: Kaufman
authors.forename: C A
authors.initials: CA
authors.lastname: Trenga
authors.forename: J
authors.initials: J
authors.lastname: Allen
authors.forename: A
authors.initials: A
authors.lastname: Peretz
authors.forename: J H
authors.initials: JH
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000393:Air Pollutants; D015415:Biomarkers / Q000378:metabolism*; D002248:Carbon Monoxide / Q000097:blood; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D009585:Nitrogen Dioxide / Q000097:blood; D052638:Particulate Matter; D013927:Thrombosis / Q000097:blood*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D001335:Vehicle Emissions; D009569:Nitric Oxide; D002248:Carbon Monoxide; D009585:Nitrogen Dioxide