Peinemann et al. Endothelial dysfunction, reduction of vascular reactivity, and autonomic imbalance might be underlying physiologic pathways leading to an increase in blood pressure, although the exact mechanisms remain to be elucidated. A further potential mechanistic pathway is the elicitation of oxidative stress and the induc- tion of a systemic inflammatory response, which are both related to atherogenesis and cardiovascular events (Libby et al. 2009). The difference between the crude and adjusted estimates from the linear regression analysis is remarkable and can be explained by confounding by age, which is strongly associ- ated with both exposure and outcome. We restricted covariates in the main model to vari- ables that we defined a priori as necessary con- founders based on a directed acyclic graph (sex, age, length of education, employment status). Adjusting for other cardiovascular risk factors attenuated the estimated percent change but did not markedly influence the OR for pres- ence of CAC. Adjusting for SES may have reduced confounding due to factors such as antioxidant intake, which is related to SES. Prior studies have examined the association of SHS with different morphologic markers of atherosclerosis, making direct comparisons across studies difficult. The size of the estimated effect in our study was comparable to a 3-year increase in vascular age in middle-age men, which represents a clinically relevant effect of SHS. In women and in the elderly, the effect on coronary age was diminished. As expected, the estimated effect was much smaller than the effect of active smoking (Jöckel et al. 2009). One important limitation of this study is its small sample size, leading to an imprecise estimation of effects, manifesting as broad CIs. Even though the complete cohort con- sists of almost 5,000 participants, we included only never-smokers in the analysis of SHS exposure. Because the prevalence of smoking in Germany is still high, only 39% of the Heinz Nixdorf Recall Study participants were never-smokers. Among these never-smokers, only a relatively low proportion (22%) of par- ticipants were considered exposed to SHS, in contrast to an estimated 55% exposure in the general adult population (Deutsches Krebsforschungszentrum 2005). This appar- ent discrepancy can be explained by three fac- tors: a) The type of SHS assessment required frequent exposure to SHS. b) Never-smokers are a select population, socializing less with smokers compared with the general popula- tion. c) We restricted our study population to the age range of 45–74 years, which does not include younger subjects with probable higher and more frequent SHS exposure. The other major limitation of this study is the comparatively crude assessment of SHS exposure. The question whether participants “frequently stay in rooms where people smoke 1560 at work, at home, or at other places” may not clearly distinguish between an exposure that happened only recently and a life-long expo- sure. Moreover, current exposure does not necessarily reflect long-term past exposure, and the validity of self-reported SHS expo- sure in general may be compromised by poor recall. The lack of information on the exposure period and the average intensity of exposure to SHS prevented a more refined analysis of the exposure–response relationship and may have contributed to misclassification of exposure (Thun et al. 1999). However, nondifferential misclassification of a binary exposure biases the effect toward the null. Therefore, the true size of the association might actually be higher than estimated in the present analyses. Although we did not take the specific type of occupation into consideration, some of which might be associated with dust exposure and SHS, we adjusted for educational attainment. The lack of biomarker information such as urinary cotinine is not considered a major limi- tation in this analysis, because coronary ath- erosclerosis takes many years to develop and is not influenced by short-term exposure during the days before outcome assessment. However, biomarker information could have helped to validate self-reported smoking status and might have prevented the unintended inclusion of active smokers in the study population. This study is a cross-sectional analysis and therefore does not allow direct conclusions regarding the development and progression of atherosclerosis. Future analyses in this cohort study with repeated measurements of CAC will investigate the progression of CAC in relation to SHS exposure. Strengths of the study include the precise and reliable assessment of coronary athero- sclerosis (CAC measured by EBCT) and the detailed and standardized assessment of car- diovascular risk factors in a large population- based cohort. Conclusions Self-reported frequent exposure to SHS was associated with subclinical coronary athero- sclerosis in our cross-sectional study popula- tion. Considering the widespread exposure and the clinical relevance of coronary athero- sclerosis, this result, if confirmed, is of public health importance. Ref Rencs Agarwal S. 2009. The association of active and passive smoking with peripheral arterial disease: results from NHANES 1999–2004. Angiology 60(3):335–345. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. 1990. Quantification of coro- nary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15(4):827–832. Barnoya J, Glantz SA. 2005. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 111(20):2684–2698. 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 scien- tific statement from the American Heart Association. Circulation 121(21):2331–2378. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. 2008. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 358(13):1336–1345. Deutsches Krebsforschungszentrum. 2005. Tobacco prevention and control (5). Secondhand smoke—an interestimated health risk [in German]. Heidelberg:Deutsches Krebsforschungszentrum. Erbel R, Möhlenkamp S, Moebus S, Schmermund A, Lehmann N, Stang A, et al. 2010. Coronary risk stratifica- tion, discrimination, and reclassification improvement based on quantification of subclinical coronary athero- sclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol 56(17):1397–1406. Folsom AR, Kronmal RA, Detrano RC, O’Leary DH, Bild DE, Bluemke DA, et al. 2008. Coronary artery calcification compared with carotid intima-media thickness in the pre- diction of cardiovascular disease incidence: the Multi- Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 168(12):1333–1339. Geerts CC, Bots ML, Grobbee DE, Uiterwaal CS. 2008. Parental smoking and vascular damage in young adult offspring: is early life exposure critical? The Atherosclerosis Risk in Young Adults study. Arterioscler Thromb Vasc Biol 28(12):2296–2302. Glymour MM, Greenland S. 2008. Chapter 12: Causal diagrams. In: Modern Epidemiology, Vol 3 (Rothman KJ, Greenland S, Lash TL, eds). Philadelphia:Lippincott Williams & Wilkins, 183–209. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, et al. 2007. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global car- diovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography). Circulation 115(3):402–426. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. 2004. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 291(2):210–215. Greenland S, Pearl J, Robins JM. 1999. Causal diagrams for epidemiologic research. Epidemiology 10(1):37–48. He Y, Lam TH, Jiang B, Wang J, Sai X, Fan L, et al. 2008. Passive smoking and risk of peripheral arterial disease and ischemic stroke in Chinese women who never smoked. Circulation 118(15):1535–1540. Jöckel KH, Lehmann N, Jaeger BR, Moebus S, Möhlenkamp S, Schmermund A, et al. 2009. Smoking cessation and sub- clinical atherosclerosis—results from the Heinz Nixdorf Recall Study. Atherosclerosis 203(1):221–227. Kiechl S, Werner P, Egger G, Oberhollenzer F, Mayr M, Xu Q, et al. 2002. Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study. Stroke 33(9):2170–2176. Knight-Lozano CA, Young CG, Burow DL, Hu ZY, Uyeminami D, Pinkerton KE, et al. 2002. Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular tissues. Circulation 105(7):849–854. Knoflach M, Kiechl S, Penz D, Zangerle A, Schmidauer C, Rossmann A, et al. 2009. Cardiovascular risk factors and ath- erosclerosis in young women: atherosclerosis risk factors in female youngsters (ARFY study). Stroke 40(4):1063–1069. Leone A, Balbarini A. 2008. Exposure to passive smoking: a test to predict endothelial dysfunction and atherosclerotic lesions. Angiology 59(2):220–223. Libby P, Ridker PM, Hansson GK. 2009. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54(23):2129–2138. Mack WJ, Islam T, Lee Z, Selzer RH, Hodis HN. 2003. Environmental tobacco smoke and carotid arterial stiff- ness. Prev Med 37(2):148–154. Matturri L, Ottaviani G, Lavezzi AM. 2005. Early atherosclerotic lesions in infancy: role of parental cigarette smoking. Virchows Arch 447(1):74–80. Schmermund A, Möhlenkamp S, Berenbein S, Pump H, Moebus S, Roggenbuck U, et al. 2006. Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography. Atherosclerosis 185(1):177–182. ovlume 119 | number 11 | November 2011 • Environmental Health Perspectives