Living Near Major Traffic Roads and Risk of Deep Vein Thrombosis Andrea Baccarelli, MD; Ida Martinelli, MD, PhD; Valeria Pegoraro, BStat; Steven Melly, MS; Paolo Grillo, MD; Antonella Zanobetti, PhD; Lifang Hou, MD; Pier Alberto Bertazzi, MD; Pier Mannuccio Mannucci, MD; Joel Schwartz, PhD Background—Particulate air pollution has been consistently linked to increased risk of arterial cardiovascular disease. Few data on air pollution exposure and risk of venous thrombosis are available. We investigated whether living near major traffic roads increases the risk of deep vein thrombosis (DVT), using distance from roads as a proxy for traffic exposure. Methods and Results—From 1995 through 2005, we examined 663 patients with DVT of the lower limbs and 859 age-matched controls from cities with population 15 000 inhabitants in Lombardia Region, Italy. We assessed distance from residential addresses to the nearest major traffic road using geographic information system methodology. The risk of DVT was estimated from logistic regression models adjusting for multiple clinical and environmental covariates. The risk of DVT was increased (odds ratio=1.33; 95% confidence interval, 1.03 to 1.71; P=0.03 in age-adjusted models; odds ratio=1.47; 95% confidence interval, 1.10 to 1.96; P=0.008 in models adjusted for multiple covariates) for subjects living near a major traffic road (index distance of 3 meters, 10th centile of the distance distribution) compared with those living farther away (reference distance of 245 meters, 90th centile). The increase in DVT risk was approximately linear over the observed distance range (from 718 to 0 meters) and was not modified after adjusting for background levels of particulate matter (odds ratio=1.47; 95% confidence interval, 1.11 to 1.96; P=0.008 for 10th versus 90th distance centile in models adjusting for area levels of particulate matter 10 m in aerodynamic diameter in the year before diagnosis). Conclusions—Living near major traffic roads is associated with increased risk of DVT. (Circulation. 2009;119:3118-3124.) Key Words: deep vein thrombosis  air pollution  risk factors  coagulation E xposure to particulate air pollution has been consistently associated with increased morbidity and death from heart disease and stroke. 1–4 Among the mechanistic pathway that mediates such effects, 4,5 elevated plasma levels of coagula- tion proteins, such as factor VIII, von Willebrand factor, and fibrinogen, as well as shortened prothrombin time, have been associated with the exposure. 5–8 Recently, an association between particulate air pollution and an increased risk of deep vein thrombosis (DVT) was reported by some of us. 9 Deter- minants of arterial and venous thrombosis are in part different, as hypercoagulability due to a series of heritable or acquired risk factors—including the gain-of-function mutations in coagulation factor V (factor V Leiden) and prothrombin (prothrombin G20210A); deficiencies of the natural anticoagulant proteins antithrombin, protein C, and protein S; and use of oral contra- ceptive or hormone replacement therapy 10 –12 —is much more frequently associated with venous than arterial thrombosis. Venous thromboembolism is the third most common cardio- vascular disease behind acute coronary syndromes and stroke. 13 In our previous study on DVT conducted in Lom- bardia Region, Italy, the average background ambient concen- trations of ambient particulate matter 10 m in aerodynamic diameter (PM 10 ) measured in the year before diagnosis in the areas of residence of the study subjects were positively associ- ated with DVT risk, and air pollution–related risks were found to be stronger in men than in women, particularly those using oral contraceptives or hormone replacement therapy. 9 After this initial report, additional evidence is needed to confirm the link between air pollution and DVT and identify the responsible sources of exposure. 14,15 Editorial see p 3050 Clinical Perspective on p 3124 Road traffic is a major determinant of exposure to partic- ulate pollution in urban environments, 16,17 and residential proximity to major traffic roads has been used in several studies to demonstrate the effects of traffic-related air pollu- tion on cardiovascular and respiratory disease. 16 –24 In the Received November 15, 2008; accepted April 6, 2009. From the Department of Environmental and Occupational Health (A.B., V.P., P.G., P.A.B.), and A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties (I.M., P.M.M.), Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Milan, Italy, Department of Environmental Health, Harvard School of Public Health, Boston, Mass (A.B., S.M., A.Z., J.S.), and Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill (L.H.). Correspondence to Dr Andrea Baccarelli, EPOCA Research Center for Environmental and Occupational Epidemiology, Department of Environmental and Occupational Health, Via San Barnaba 8, 20122 Milan, Italy. E-mail andrea.baccarelli@unimi.it © 2009 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.108.836163 3118 Vascular Medicine by guest on November 23, 2015 http://circ.ahajournals.org/ Downloaded from