Lead, Cadmium,Arsenic, and cardiovascular risk in children

Summary

Principal Investigator: Eliseo Guallar
Abstract: DESCRIPTION (provided by applicant): The main objective of this project is to test the hypothesis that exposure to metals in children will affect their cardiovascular risk and may predispose them to cardiovascular disease. It is based upon a growing epidemiological literature, by us and others, indicating that exposure to lead, cadmium, or arsenic increases cardiovascular risk. However, most studies of the impact of metals on cardiovascular risk have been carried out in adults, and the susceptibility of children to the cardiovascular effects of metals is largely unknown. Primary hypotheses: 1) Exposures to lead, cadmium, or arsenic are positively associated with blood pressure levels in children;2) Exposures to lead, cadmium, or arsenic, are positively associated with serological markers of inflammation and endothelial dysfunction (C-reactive protein [CRP], interleukin-6 [IL-6], intercellular adhesion molecule-1 [ICAM-1], and tumor necrosis factor alpha [TNF-alpha]) in children;and 3) Exposures, cadmium, or arsenic are inversely associated with heart rate variability in children. Design and setting: We propose to conduct a cross sectional epidemiological study of the association between exposure to lead, cadmium, or arsenic and markers of cardiovascular risk in children residing in the Torresn metropolitan area, Mexico. We will contact the children who participated in the Torresn Study of Lead and Neurocognitive Function in 2001, when they were 6 - 7 years old. We expect to recruit 512 (85%) of the original study participants, who will be 14 - 15 years old at the time of field work for the present study in 2009. This population offers a unique opportunity to evaluate the cardiovascular effects of metals in a large and well characterized group of children whose lead exposure has been previously studied. In the present study, we will obtain two measurements of metal exposure two months apart (lead in whole blood and cadmium and arsenic in urine) and evaluate their association with cardiovascular risk markers. The primary outcomes will be blood pressure, serological markers of inflammation and endothelial dysfunction (CRP, IL-6, ICAM-1, and TNF- alpha), and heart rate variability. Other endpoints will also be assessed, including markers of renal proximal tubular injury, cardiometabolic abnormalities (insulin resistance and lipid levels), and neurotoxic endpoints. Significance: Children in Torresn are exposed to lead, cadmium, and arsenic from dusts generated by the Met-Mex Peqoles smelter, the largest lead smelter operating in the Americas. While the average exposure to metals in this population is high, the range of exposure overlaps with that of children in US and in other Western countries. The current population thus represents an efficient way to obtain information on the impact of a wide range of metal exposure at the population level. The information obtained from children in Torresn will be relevant not only to local area residents, but to many children in the US and abroad. PUBLIC HEALTH RELEVANCE: The main objective of this project is to test the hypothesis that exposure to metals in children will affect their cardiovascular risk and may predispose them to later cardiovascular disease. We propose to conduct a cross- sectional epidemiological study of the association between exposure to lead, cadmium, or arsenic and markers of cardiovascular risk in children residing in the Torresn metropolitan area, Mexico. Almost all studies of the impact of metals on cardiovascular risk have been carried out in adults, and the susceptibility of children to the cardiovascular effects of metals is largely unknown. The information obtained in this study will be relevant to millions of children in the US and abroad who are chronically exposed to lead, cadmium, and arsenic in the environment.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents
    Virginia M Weaver
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Johns Hopkins University School of Medicine, Baltimore, MD, USA Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Electronic address
    Environ Res 132:226-32. 2014
  2. pmc Thyroid hormones and electrocardiographic parameters: findings from the third national health and nutrition examination survey
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    PLoS ONE 8:e59489. 2013
  3. pmc QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey
    Yiyi Zhang
    Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, 2024 E Monument Street, Baltimore, MD 21205, USA
    Arch Intern Med 171:1727-33. 2011
  4. pmc Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis
    Yiyi Zhang
    Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
    Am J Epidemiol 174:403-11. 2011
  5. pmc Electrocardiographic QT interval and mortality: a meta-analysis
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Epidemiology 22:660-70. 2011
  6. pmc Serum 25-hydroxyvitamin D, calcium, phosphorus, and electrocardiographic QT interval duration: findings from NHANES III and ARIC
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Baltimore, Maryland 21205, USA
    J Clin Endocrinol Metab 96:1873-82. 2011
  7. pmc Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
    PLoS ONE 6:e17584. 2011
  8. pmc Urine arsenic and hypertension in US adults: the 2003-2008 National Health and Nutrition Examination Survey
    Miranda R Jones
    Department of Epidemiology, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Epidemiology 22:153-61. 2011
  9. pmc Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US National Health and Nutrition Examination Survey
    Maria Tellez-Plaza
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Epidemiol 172:671-81. 2010
  10. pmc Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004
    Martin Laclaustra
    Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares CNIC, Madrid, Spain
    Atherosclerosis 210:643-8. 2010

Scientific Experts

  • Eliseo Guallar
  • Yiyi Zhang
  • Wendy S Post
  • Elena Blasco-Colmenares
  • Gordon F Tomaselli
  • Darshan Dalal
  • Ana Navas-Acien
  • Martin Laclaustra
  • Maria Tellez-Plaza
  • Virginia M Weaver
  • Elsayed Z Soliman
  • Miranda R Jones
  • A Richey Sharrett
  • Saverio Stranges
  • Jose M Ordovas
  • Marisela Rubio-Andrade
  • Patrick J Parsons
  • Stephen J Rothenberg
  • Ellen K Silbergeld
  • Jeffrey J Fadrowski
  • Gonzalo GarcĂ­a Vargas
  • Amy J Steuerwald
  • Alan Cheng
  • Sandeep Bansal
  • Alvaro Alonso
  • Suzanne Jan de Beur
  • Dhananjay Vaidya
  • Pamela Ouyang
  • Ramon Brugada
  • Eric A Whitsel
  • Ciprian M Crainiceanu

Detail Information

Publications11

  1. pmc Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents
    Virginia M Weaver
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Johns Hopkins University School of Medicine, Baltimore, MD, USA Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Electronic address
    Environ Res 132:226-32. 2014
    ..Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary...
  2. pmc Thyroid hormones and electrocardiographic parameters: findings from the third national health and nutrition examination survey
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    PLoS ONE 8:e59489. 2013
    ..However, little is known about how variations in thyroid hormone levels within the normal range affect electrical activities of the heart in the general population...
  3. pmc QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey
    Yiyi Zhang
    Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, 2024 E Monument Street, Baltimore, MD 21205, USA
    Arch Intern Med 171:1727-33. 2011
    ....
  4. pmc Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis
    Yiyi Zhang
    Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
    Am J Epidemiol 174:403-11. 2011
    ..The findings suggest that testosterone levels may explain differences in QT-interval duration between men and women and could be a contributor to population variability in QT-interval duration among men...
  5. pmc Electrocardiographic QT interval and mortality: a meta-analysis
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Epidemiology 22:660-70. 2011
    ..However, the implications of variations in QT-interval length within normal limits for mortality in the general population are still unclear...
  6. pmc Serum 25-hydroxyvitamin D, calcium, phosphorus, and electrocardiographic QT interval duration: findings from NHANES III and ARIC
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Baltimore, Maryland 21205, USA
    J Clin Endocrinol Metab 96:1873-82. 2011
    ....
  7. pmc Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey
    Yiyi Zhang
    Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
    PLoS ONE 6:e17584. 2011
    ..However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration...
  8. pmc Urine arsenic and hypertension in US adults: the 2003-2008 National Health and Nutrition Examination Survey
    Miranda R Jones
    Department of Epidemiology, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Epidemiology 22:153-61. 2011
    ..We investigated the association of exposure to inorganic arsenic (as measured in urine) with systolic and diastolic blood pressure levels and the prevalence of hypertension in US adults...
  9. pmc Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US National Health and Nutrition Examination Survey
    Maria Tellez-Plaza
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Epidemiol 172:671-81. 2010
    ..These findings add to the concern of increased cadmium exposure as a cardiovascular risk factor in the general population...
  10. pmc Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004
    Martin Laclaustra
    Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares CNIC, Madrid, Spain
    Atherosclerosis 210:643-8. 2010
    ....
  11. pmc Serum selenium concentrations and hypertension in the US Population
    Martin Laclaustra
    Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
    Circ Cardiovasc Qual Outcomes 2:369-76. 2009
    ..We explored the relationship of serum selenium concentrations with blood pressure and hypertension in a representative sample of the US population...