Chronic exposure to mercury, a highly reactive heavy metal, may increase cardiovascular disease (CVD) risk. Because the major environmental exposure to mercury is from fish intake, which may otherwise have significant cardiovascular benefits, and because adequate data are critical to ongoing policy decisions regarding mercury contaminants, elucidating the relationship between mercury and CVD risk is of great scientific and public health importance. However, results of prior studies have been inconsistent, and prior studies excluded women and did not evaluate stroke, a major cause of CVD morbidity and mortality. Selenium, an essential dietary trace element, plays an important role in antioxidant defense systems and may protect against both CVD and toxic effects of mercury. Such a protective effect would have direct implications for recommendations regarding optimal selenium intake and for assessing the potential impact of mercury contamination from fish intake in selenium-replete populations. However, the possible interaction between mercury, selenium, and cardiovascular risk is not well-established. The objectives of this application are to assess the associations between mercury and selenium exposure and risk of coronary heart disease (CHD) and stroke in women and men. It is hypothesized that: 1. Chronic mercury exposure is associated with higher risk of CVD (CHD and stroke) in women and men. 2. Selenium intake is associated with lower risk of CVD. 3. The relation between mercury levels and CVD risk varies depending on intake of selenium.
These aims will be investigated using a prospective nested case-control design among women and men participating in two large U.S. cohort studies, including 6,470 incident CVD cases. Exposures will be ascertained using stored toenail clippings, a reliable biomarker of chronic mercury and selenium intake. This study provides a unique and cost-efficient opportunity to evaluate the importance of mercury and selenium intake for cardiovascular risk in women and men. This research will greatly clarify the potential risks and benefits offish intake, mercury exposure, and selenium intake for cardiovascular disease prevention, fulfilling the NIH's mission to pursue fundamental knowledge about human health and illness and the application of that knowledge to extend healthy life and reduce burdens of death and disability.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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Cardiovascular and Sleep Epidemiology (CASE)
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Dilworth, Caroline H
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Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
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Saber, Hamidreza; Yakoob, Mohammad Yawar; Shi, Peilin et al. (2017) Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts. Stroke 48:2678-2685
Yakoob, Mohammad Y; Shi, Peilin; Willett, Walter C et al. (2016) Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts. Circulation 133:1645-54
Yakoob, Mohammad Y; Shi, Peilin; Hu, Frank B et al. (2014) Circulating biomarkers of dairy fat and risk of incident stroke in U.S. men and women in 2 large prospective cohorts. Am J Clin Nutr 100:1437-47
Lajous, Martin; Willett, Walter C; Robins, James et al. (2013) Changes in fish consumption in midlife and the risk of coronary heart disease in men and women. Am J Epidemiol 178:382-91
Mozaffarian, Dariush; Shi, Peilin; Morris, J Steven et al. (2013) Methylmercury exposure and incident diabetes in U.S. men and women in two prospective cohorts. Diabetes Care 36:3578-84
Park, Kyong; Rimm, Eric B; Siscovick, David S et al. (2012) Toenail selenium and incidence of type 2 diabetes in U.S. men and women. Diabetes Care 35:1544-51
Mozaffarian, Dariush; Shi, Peilin; Morris, J Steven et al. (2012) Mercury exposure and risk of hypertension in US men and women in 2 prospective cohorts. Hypertension 60:645-52
Mozaffarian, Dariush; Shi, Peilin; Morris, J Steven et al. (2011) Mercury exposure and risk of cardiovascular disease in two U.S. cohorts. N Engl J Med 364:1116-25
Mozaffarian, Dariush (2009) Fish, mercury, selenium and cardiovascular risk: current evidence and unanswered questions. Int J Environ Res Public Health 6:1894-916
Mozaffarian, Dariush (2009) Meat intake and mortality: evidence for harm, no effect, or benefit? Arch Intern Med 169:1537-8; author reply 1539

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