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Pirkle JL, Schwartz J, Landis JR, Harlan WR. The relationship between blood lead levels and blood pressure and its cardiovascular risk implications.  Am J Epidemiol.1985;121:246-258.Google Scholar
Kopp SJ, Barron JT, Tow JP. Cardiovascular actions of lead and relationship to hypertension: a review.  Environ Health Perspect.1988;78:91-99.Google Scholar
Burt VL, Whelton P, Roccella EJ.  et al.  Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988-1991.  Hypertension.1995;25:305-313.Google Scholar
Hertz-Picciotto I, Croft J. Review of the relation between blood lead and blood pressure.  Epidemiol Rev.1993;15:352-373.Google Scholar
Nowack R, Wiecek A, Exner B, Gretz N, Ritz E. Chronic lead exposure in rats: effects on blood pressure.  Eur J Clin Invest.1993;23:433-443.Google Scholar
Vander AJ. Chronic effects of lead on the renin-angiotensin system.  Environ Health Perspect.1988;78:77-83.Google Scholar
Korrick SA, Hunter DJ, Rotnitzky A, Hu H, Speizer FE. Lead and hypertension in a sample of middle-aged women.  Am J Public Health.1999;89:330-335.Google Scholar
Cowley Jr AW, Roman RJ. The role of the kidney in hypertension.  JAMA.1996;275:1581-1589.Google Scholar
Hu H, Aro A, Payton M.  et al.  The relationship of bone and blood lead to hypertension: the Normative Aging Study.  JAMA.1996;275:1171-1176.Google Scholar
Brody DJ, Pirkle JL, Kramer RA.  et al.  Blood lead levels in the US population: phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1991).  JAMA.1994;272:277-283.Google Scholar
Gulson BL, Mahaffey KR, Mizon KJ.  et al.  Contribution of tissue lead to blood lead in adult female subjects based on stable lead isotope methods.  J Lab Clin Med.1995;125:703-712.Google Scholar
Gulson BL, Jameson CW, Mahaffey KR.  et al.  Pregnancy increases mobilization of lead from maternal skeleton.  J Lab Clin Med.1997;130:51-62.Google Scholar
Smith DR, Osterloh JD, Flegal AR. Use of endogenous, stable lead isotopes to determine release of lead from the skeleton.  Environ Health Perspect.1996;104:60-66.Google Scholar
Silbergeld EK, Schwartz J, Mahaffey K. Lead and osteoporosis: mobilization of lead from bone in postmenopausal women.  Environ Res.1988;47:79-94.Google Scholar
Symanski E, Hertz PI. Blood lead levels in relation to menopause, smoking, and pregnancy history.  Am J Epidemiol.1995;141:1047-1058.Google Scholar
Muldoon SB, Cauley JA, Allen L. Effect of bone mineral density changes on blood lead levels in peri-menopausal women. Paper presented at: Society for Epidemiologic Research; June 1997; Calgary, Alberta.
Nash D, Silbergeld E, Magder L, Stolley P. Menopause, hormone replacement therapy (HRT), and blood lead levels among adult women from NHANES III, 1988-1994 [abstract].  Am J Epidemiol.1998;147:S93.Google Scholar
Silbergeld E, Nash D. Lead and human health: is this mine exhausted.  Progress in Environmental Science.2000;1:53-68.Google Scholar
Pirkle JL, Brody DJ, Gunter EW.  et al.  The decline in blood lead levels in the United States: the National Health and Nutrition Examination Surveys (NHANES).  JAMA.1994;272:284-291.Google Scholar
Harlan WR. The relationship of blood lead levels to blood pressure in the US population.  Environ Health Perspect.1988;78:9-13.Google Scholar
Harlan WR, Landis JR, Schmouder RL.  et al.  Blood lead and blood pressure: relationship in the adolescent and adult US population.  JAMA.1985;253:530-534.Google Scholar
Pocock SJ, Shaper AG, Ashby D.  et al.  The relationship between blood lead, blood pressure, stroke, and heart attacks in middle-aged British men.  Environ Health Perspect.1988;78:23-30.Google Scholar
Neri LC, Hewitt D, Orser B. Blood lead and blood pressure: analysis of cross-sectional and longitudinal data from Canada.  Environ Health Perspect.1988;78:123-126.Google Scholar
Elwood PC, Davey-Smith G, Oldham PD, Toothill C. Two Welsh surveys of blood lead and blood pressure.  Environ Health Perspect.1988;78:119-121.Google Scholar
Elwood PC, Yarnell JW, Oldham PD.  et al.  Blood pressure and blood lead in surveys in Wales.  Am J Epidemiol.1988;127:942-945.Google Scholar
Sharp DS, Becker CE, Smith AH. Chronic low-level lead exposure: its role in the pathogenesis of hypertension.  Med Toxicol.1987;2:210-232.Google Scholar
Sharp DS, Osterloh J, Becker CE.  et al.  Blood pressure and blood lead concentration in bus drivers.  Environ Health Perspect.1988;78:131-137.Google Scholar
Sharp DS, Osterloh J, Becker CE.  et al.  Elevated blood pressure in treated hypertensives with low-level lead accumulation.  Arch Environ Health.1989;44:18-22.Google Scholar
Moller L, Kristensen TS. Blood lead as a cardiovascular risk factor.  Am J Epidemiol.1992;136:1091-1100.Google Scholar
Proctor SP, Rotnitzky A, Sparrow D.  et al.  The relationship of blood lead and dietary calcium to blood pressure in the normative aging study.  Int J Epidemiol.1996;25:528-536.Google Scholar
Staessen JA, Roels H, Fagard R. Lead exposure and conventional and ambulatory blood pressure: a prospective population study.  JAMA.1996;275:1563-1570.Google Scholar
Staessen J, Sartor F, Roels H.  et al.  The association between blood pressure, calcium and other divalent cations: a population study.  J Hum Hypertens.1991;5:485-494.Google Scholar
Hense HW, Filipiak B, Keil U. The association of blood lead and blood pressure in population surveys.  Epidemiology.1993;4:173-179.Google Scholar
Hense HW, Filipiak B, Keil U. Alcohol consumption as a modifier of the relation between blood lead and blood pressure.  Epidemiology.1994;5:120-123.Google Scholar
Grandjean P, Hollnagel H, Hedegaard L.  et al.  Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders.  Am J Epidemiol.1989;129:732-739.Google Scholar
Schwartz J. The relationship between blood lead and blood pressure in the NHANES II survey.  Environ Health Perspect.1988;78:15-22.Google Scholar
Schwartz J. Lead, blood pressure, and cardiovascular disease in men and women.  Environ Health Perspect.1991;91:71-75.Google Scholar
Schwartz J. Lead, blood pressure, and cardiovascular disease in men.  Arch Environ Health.1995;50:31-37.Google Scholar
Reckelhoff JH. Gender differences in the regulation of blood pressure.  Hypertension.2001;37:1199-1208.Google Scholar
Ezzati T, Massey J, Waksburg J.  et al.  Sample Design: Third National Health and Nutrition Examination Survey. Hyattsville, Md: Dept of Health and Human Services, National Center for Health Statistics; 1992. Publication PHS 92-1387.
Kim R, Rotnitsky A, Sparrow D.  et al.  A longitudinal study of low-level lead exposure and impairment of renal function: the Normative Aging Study.  JAMA.1996;275:1177-1181.Google Scholar
Silbergeld E, Watson L. Exposure to lead during reproduction and menopause.  Fundam Appl Toxicol.1995;25:167-168.Google Scholar
Muldoon SB, Cauley JA, Kuller LH.  et al.  Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women.  Am J Epidemiol.1994;139:599-608.Google Scholar
Staessen JA, Celis H, Fagard R. The epidemiology of the association between hypertension and menopause.  J Hum Hypertens.1998;12:587-592.Google Scholar
Hu FB, Grodstein F. Postmenopausal hormone therapy and the risk of cardiovascular disease: the epidemiologic evidence.  Am J Cardiol.2002;90:26F-29F.Google Scholar
Batuman V, Landy E, Maesaka JK, Wedeen RP. Contribution of lead to hypertension with renal impairment.  N Engl J Med.1983;309:17-21.Google Scholar
Staessen J. Low-level lead exposure, renal function and blood pressure.  Verh K Acad Geneeskd Belg.1995;57:527-574.Google Scholar
Sharp DS, Benowitz NL, Osterloh JD.  et al.  Influence of race, tobacco use, and caffeine use on the relation between blood pressure and blood lead concentration.  Am J Epidemiol.1990;131:845-854.Google Scholar
Lindquist O, Bengtsson C, Hansson T, Roos B. Bone mineral content in relation to age and menopause in middle-aged women: a study of bone density in lumbar vertebrae by dual photon absorptiometry in a population sample of women.  Scand J Clin Lab Invest.1981;41:215-223.Google Scholar
Krolner B, Pors NS. Bone mineral content of the lumbar spine in normal and osteoporotic women: cross-sectional and longitudinal studies.  Clin Sci.1982;62:329-336.Google Scholar
Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling.  J Lab Clin Med.1978;92:964-970.Google Scholar
Lindsay R, Hart DM, Aitken JM.  et al.  Long-term prevention of postmenopausal osteoporosis by estrogen: evidence for an increased bone mass after delayed onset of estrogen treatment.  Lancet.1976;1:1038-1041.Google Scholar
Riggs BL, Melton Ld. Involutional osteoporosis.  N Engl J Med.1986;314:1676-1686.Google Scholar
Nordin B. Osteoporosis with particular reference to the menopause. In: Alvioli L, ed. The Osteoporotic Syndrome: Detection, Prevention, and Treatment. New York, NY: Grune & Stratton; 1983.
Lagerkvist BJ, Soderberg HA, Nordberg GF.  et al.  Biological monitoring of arsenic, lead and cadmium in occupationally and environmentally exposed pregnant women.  Scand J Work Environ Health.1993;19 Suppl 1:50-53.Google Scholar
Knight EM, Spurlock BG, Edwards CH.  et al.  Biochemical profile of African American women during three trimesters of pregnancy and at delivery.  J Nutr.1994;124:943S-953S.Google Scholar
West WL, Knight EM, Edwards CH.  et al.  Maternal low level lead and pregnancy outcomes.  J Nutr.1994;124:981S-986S.Google Scholar
Webber CE, Chettle DR, Bowins RJ.  et al.  Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.  Environ Health Perspect.1995;103:1150-1153.Google Scholar
Grandjean P, Nielsen GD, Jorgensen PJ, Horder M. Reference intervals for trace elements in blood: significance of risk factors.  Scand J Clin Lab Invest.1992;52:321-337.Google Scholar
Hu H, Rabinowitz M, Smith D. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.  Environ Health Perspect.1998;106:1-8.Google Scholar
Cake KM, Bowins RJ, Vaillancourt C.  et al.  Partition of circulating lead between serum and red cells is different for internal and external sources of lead.  Am J Ind Med.1996;29:440-445.Google Scholar
Lustberg M, Silbergeld E. Blood lead levels and mortality.  Arch Intern Med.2002;162:2443-2449.Google Scholar
Original Contribution
March 26, 2003

Blood Lead, Blood Pressure, and Hypertension in Perimenopausal and Postmenopausal Women

Author Affiliations

Author Affiliations: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore (Drs Nash, Magder, Lustberg, Sherwin, and Silbergeld); New York City Department of Health and Mental Hygiene, HIV/AIDS Surveillance and Epidemiology Program, New York (Dr Nash); Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La (Dr Sherwin); Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md (Dr Rubin); and National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Kaufmann). Dr Silbergeld is now with the Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.

JAMA. 2003;289(12):1523-1532. doi:10.1001/jama.289.12.1523

Context Lead exposures have been shown to be associated with increased blood pressure and risk of hypertension in older men. In perimenopausal women, skeletal lead stores are an important source of endogenous lead exposure due to increased bone demineralization.

Objective To examine the relationship of blood lead level with blood pressure and hypertension prevalence in a population-based sample of perimenopausal and postmenopausal women in the United States.

Design, Setting, and Participants Cross-sectional sample of 2165 women aged 40 to 59 years, who participated in a household interview and physical examination, from the Third National Health and Nutrition Examination Survey conducted from 1988 to 1994.

Main Outcome Measures Associations of blood lead with blood pressure and hypertension, with age, race and ethnicity, cigarette smoking status, body mass index, alcohol use, and kidney function as covariates.

Results A change in blood lead levels from the lowest (quartile 1: range, 0.5-1.6 µg/dL) to the highest (quartile 4: range, 4.0-31.1 µg/dL) was associated with small statistically significant adjusted changes in systolic and diastolic blood pressures. Women in quartile 4 had increased risks of diastolic (>90 mm Hg) hypertension (adjusted odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.7), as well as moderately increased risks for general hypertension (adjusted OR, 1.4; 95% CI, 0.92-2.0) and systolic (>140 mm Hg) hypertension (adjusted OR, 1.5; 95% CI, 0.72-3.2). This association was strongest in postmenopausal women, in whom adjusted ORs for diastolic hypertension increased with increasing quartile of blood lead level compared with quartile 1 (adjusted OR, 4.6; 95% CI, 1.1-19.2 for quartile 2; adjusted OR, 5.9; 95% CI, 1.5-23.1 for quartile 3; adjusted OR, 8.1; 95% CI, 2.6-24.7 for quartile 4).

Conclusions At levels well below the current US occupational exposure limit guidelines (40 µg/dL), blood lead level is positively associated with both systolic and diastolic blood pressure and risks of both systolic and diastolic hypertension among women aged 40 to 59 years. The relationship between blood lead level and systolic and diastolic hypertension is most pronounced in postmenopausal women. These results provide support for continued efforts to reduce lead levels in the general population, especially women.