| Dioxins and Cardiovascular Disease Mortality Olivier Humblet,1 Linda Birnbaum,2 Eric Rimm,3,4 Murray A. Mittleman,3,5 and Russ Hauser1,3 1Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 2Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 3Department of Epidemiology, and 4Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA; 5Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Abstract
Objective: In this systematic review we evaluated the evidence on the association between dioxin exposure and cardiovascular disease (CVD) mortality in humans. Data sources and extraction: We conducted a PubMed search in December 2007 and considered all English-language epidemiologic studies and their citations regarding dioxin exposure and CVD mortality. To focus on dioxins, we excluded cohorts that were either primarily exposed to polychlorinated biphenyls or from the leather and perfume industries, which include other cardiotoxic coexposures. Data synthesis: We included results from 12 cohorts in the review. Ten cohorts were occupationally exposed. We divided analyses according to two well-recognized criteria of epidemiologic study quality: the accuracy of the exposure assessment, and whether the exposed population was compared with an internal or an external (e.g., general population) reference group. Analyses using internal comparisons with accurate exposure assessments are the highest quality because they minimize both exposure misclassification and confounding due to workers being healthier than the general population ("healthy worker effect") . The studies in the highest-quality group found consistent and significant dose-related increases in ischemic heart disease (IHD) mortality and more modest associations with all-CVD mortality. Their primary limitation was a lack of adjustment for potential confounding by the major risk factors for CVD. Conclusions: The results of this systematic review suggest that dioxin exposure is associated with mortality from both IHD and all CVD, although more strongly with the former. However, it is not possible to determine the potential bias, if any, from confounding by other risk factors for CVD. Key words: cardiovascular disease, dioxin, epidemiology, healthy worker effect, herbicides, ischemic heart disease, mortality, occupational exposure, PCB, TCDD. Environ Health Perspect 116:1443–1448 (2008) . doi:10.1289/ehp.11579 available via http://dx.doi.org/ [Online 22 July 2008]
Address correspondence to R. Hauser, Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Building I, Room 1405, Boston, MA 02115 USA. Telephone: (617) 432-3326. Fax: (617) 432-0219. E-mail: rhauser@hohp.harvard.edu We thank G. Rice and M. DeVito of the U.S. EPA for thoughtful comments on the manuscript. O.H. is supported by National Institute for Occupational Safety and Health training grant T42 OH008416-04. This report has been reviewed by the U.S. EPA's Office of Research and Development and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 14 April 2008 ; accepted 22 July 2008.
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