based on a central-site monitor. Although some exposure misclassification will still occur based on our model estimates, we expect that most of the residual error is Berkson type, based on a previous validation study for this model analyzing measurement error (Gryparis et al. 2009). Thus, we expect that the exposure misclassification will not bias effect estimates. The lack of individual activity data also presents a limitation, but the NAS population consists of elderly men who spend a consider- able amount of time at or near their home address compared with other population groups. Our sensitivity analysis of the block lags of weeks 5–8 and weeks 9–12 shows slight attenuation compared with the cumulative lags, suggesting that the cumulative effect may be dominated by the more recent weeks. The effect sizes for cumulative exposures do not attenuate when averaged up to 12 weeks. The 4-week block lags do not isolate the effects of those time windows because each week is cor- related in both space and time; thus, future studies to model the specific contributions of different lag weeks would be beneficial in understanding these effects. Sources and components. Many studies have examined PM at different diameters, but fewer studies have looked at which compo- nents of PM are associated with adverse health effects. Our study links a health biomarker with BC, a specific component of PM2.5. In addition, we consider BC to be a surrogate for primary traffic PM (a specific source of air pollution), where the spatial variability of BC on a given day reflects the variability of traffic in the region, which is the basis of the BC model we developed and used for this study. We did not examine other pollutants such as total PM2.5 or PM2.5 components other than BC in this study. We think it is unlikely that total PM2.5 or any other copollutant is driving the effect we observed for BC because the BC model is based largely on the daily spatial variation exhibited by BC. Other com- ponents of PM2.5, such as sulfates and organic PM, are more homogeneous over the study region. Although we cannot completely rule out confounding by copollutants or other factors, the correlation between the model- predicted 4-week BC and the correspond- ing 4-week averages of PM2.5 measured at the central site was low (0.108), which sup- ports our belief that the effects observed are not driven by any temporal correlation with PM2.5 or one of its components. Generalizability. A limitation of this study is the restricted demographics of the study population. Study subjects were all elderly men, most of them white. Thus, we cannot generalize our results to other populations. However, the elderly represent a particularly susceptible population, and the growth in the number and proportion of older adults in the United States is unprecedented: by 2030, the proportion of the U.S. population ≥ 65 years of age will double to about 71 million older adults, or one in every five Americans (U.S. Census 2005). Conclusions We observed positive associations between BC exposures and blood levels of sICAM-1 and sVCAM-1, with statistically significant effect estimates for sICAM-1 in the popula- tion as a whole and for sVCAM-1 among diabetics and participants who were not using statins. Effects of BC on both markers appeared to be limited to diabetics and pos- sibly those not using statins. Overall, our results suggest that exposure to traffic PM over 4–12 weeks may induce an increased inflammatory and endothelial response, par- ticularly among diabetics, and that statin use may be protective against this effect. Ref Rencs Albert MA, Danielson E, Rifai N, Ridker PM. 2001. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286(1):64–70. Albert MA, Ridker PM. 1999. The role of C-reactive protein in cardiovascular disease risk. Curr Cardiol Rep 1(2):99–104. Bell B, Rose C, Damon A. 1972. The Normative Aging Study: an interdisciplinary and longitudinal study of health and aging. Aging Hum Dev 3:4–17. Blanco-Colio LM, Martin-Ventura JL, de Teresa E, Farsang C, Gaw A, Gensini G, et al. 2007. Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration. Am Heart J 153(5):881–888. Brauer M, Hoek G, van Vliet P, Meliefste K, Fischer P, Gehring U, et al. 2003. Estimating long-term average particulate air pollution concentrations: application of traffic indica- tors and geographic information systems. Epidemiology 14(2):228–239. Brook RD, Rajagopalan S, Pope CA III, Brook JR, Bhatnagar A, Diez-Roux AV, et al. 2010. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121(21):2331–2378. Brunekreef B, Beelen R, Hoek G, Schouten L, Bausch- Goldbohm S, Fischer P, et al. 2009. Effects of long-term exposure to traffic-related air pollution on respiratory and cardiovascular mortality in the Netherlands: the NLCS-AIR study. Res Rep Health Eff Inst (139):5–89. Calles-Escandon J, Cipolla M. 2001. Diabetes and endothelial dysfunction: a clinical perspective. Endocr Rev 22(1):36–52. Clougherty JE, Wright RJ, Baxter LK, Levy JI. 2008. Land use regression modeling of intra-urban residential variability in multiple traffic-related air pollutants. Environ Health 7:17; doi:10.1186/1476-069X-7-17 [Online 16 May 2008]. Delfino RJ, Staimer N, Tjoa T, Polidori A, Arhami M, Gillen DL, et al. 2008. Circulating biomarkers of inflammation, anti- oxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coro- nary artery disease. Environ Health Perspect 116:898–906. Eschen O, Christensen JH, Dethlefsen C, Schmidt EB. 2008. Cellular adhesion molecules in healthy subjects: short term variations and relations to flow mediated dilation. Biomark Insights 3:57–62. Forastiere F, Stafoggia M, Berti G, Bisanti L, Cernigliaro A, Chiusolo M, et al. 2008. Particulate matter and daily mor- tality: a case-crossover analysis of individual effect modi- fiers. Epidemiology 19(4):571–580. Gehring U, Heinrich J, Kramer U, Grote V, Hochadel M, Sugiri D, Environmental Health Perspectives • volume 119 | number 4 | April 2011 Traffic particles and endothelial function et al. 2006. Long-term exposure to ambient air pollution and cardiopulmonary mortality in women. Epidemiology 17(5):545–551. Ghio AJ, Kim C, Devlin RB. 2000. Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Resp Crit Care Med 162(3 pt 1):981–988. Gryparis A, Coull BA, Schwartz J, Suh HH. 2007. Semiparametric latent variable regression models for spatiotemporal mod- eling of mobile source particles in the Greater Boston area. Appl Stat 56(2):183–209. Gryparis A, Paciorek CJ, Zeka A, Schwartz J, Coull BA. 2009. Measurement error caused by spatial misalignment in environmental epidemiology. Biostatistics 10(2):258–274. Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S. 2004. Antioxidant effects of statins via S-nitrosylation and acti- vation of thioredoxin in endothelial cells: a novel vasculo- protective function of statins. Circulation 110(7):856–861. Kinney PL, Aggarwal M, Northridge ME, Janssen NA, Shepard P. 2000. Airborne concentrations of PM2.5 and diesel exhaust particles on Harlem sidewalks: a community-based pilot study. Environ Health Perspect 108:213–218. Liang YJ, Shyu KG, Wang BW, Lai LP. 2008. Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products. Cardiology 110(3):182–190. Lim SC, Caballero AE, Smakowski P, LoGerfo FW, Horton ES, Veves A. 1999. Soluble intercellular adhesion molecule, vas- cular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 dia- betic individuals without microalbuminuria. Diabetes Care 22(11):1865–1870. Madrigano J, Baccarelli A, Wright R, Suh H, Sparrow D, Vokonas P, et al. 2010. Air pollution, obesity, genes, and cellular adhesion molecules. Occup Environ Med 67(5):312–317. Maynard D, Coull BA, Gryparis A, Schwartz J. 2007. Mortality risk associated with short-term exposure to traffic particles and sulfates. Environ Health Perspect 115:751–755. Montecucco F, Burger F, Pelli G, Poku NK, Berlier C, Steffens S, et al. 2009. Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes. Rheumatology (Oxford) 48(3):233–242. O’Neill MS, Veves A, Sarnat JA, Zanobetti A, Gold DR, Economides PA, et al. 2007. Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med 64(6):373–379. O’Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, et al. 2005. Diabetes enhances vulner- ability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 111(22):2913–2920. Park SK, O’Neill MS, Vokonas PS, Sparrow D, Spiro A III, Tucker KL, et al. 2008. Traffic-related particles are associ- ated with elevated homocysteine: the VA Normative Aging Study. Am J Resp Crit Care Med 178(3):283–289. Pradhan AD, Rifai N, Ridker PM. 2002. Soluble intercellular adhe- sion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation 106(7):820–825. Rana JS, Arsenault BJ, Després JP, Côté M, Talmud PJ, Ninio E, et al. 2011. Inflammatory biomarkers, physical activity, waist circumference, and risk of future coronary heart dis- ease in healthy men and women. Eur Heart J 32(3):336–344. Ren C, Park SK, Vokonas PS, Sparrow D, Wilker E, Baccarelli A, et al. 2010. Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of par- ticulate air pollution. Epidemiology 21(2):198–206. Ridker PM, Buring JE, Cook NR, Rifai N. 2003. C-reactive pro- tein, the metabolic syndrome, and risk of incident cardio- vascular events: an 8-year follow-up of 14719 initially healthy American women. Circulation 107(3):391–397. Salvi S, Blomberg A, Rudell B, Kelly F, Sandstrom T, Holgate ST, et al. 1999. Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers. Am J Resp Crit Care Med 159(3):702–709. Schneider A, Neas L, Herbst MC, Case M, Williams RW, Cascio W, et al. 2008. Endothelial dysfunction: associa- tions with exposure to ambient fine particles in diabetic individuals. Environ Health Perspect 116:1666–1674. Schwartz J. 2001. Air pollution and blood markers of cardio- vascular risk. Environ Health Perspect 109(suppl 3):405–409. 485