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April 17, 1996, Vol 275, No. 15 >
ARTICLE | April 17, 1996

The Relationship of Bone and Blood Lead to Hypertension: Title and subTitle BreakThe Normative Aging Study FREE

Howard Hu, MD, ScD; Antonio Aro, PhD; Marinelle Payton, MD, PhD; Susan Korrick, MD, MPH; David Sparrow, DSc; Scott T. Weiss, MD, MS; Andrea Rotnitzky, PhD
[+] Author Affiliations

Reprints: Howard Hu, MD, Channing Laboratory, 180 Longwood Ave, Boston, MA 02115 (e-mail: rehhu@ gauss.med.harvard.edu).


JAMA. 1996;275(15):1171-1176. doi:10.1001/jama.1996.03530390037031
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References

Objective.  —To test the hypothesis that long-term lead accumulation, as reflected by levels of lead in bone (as opposed to blood, which reflects recent lead exposure), is associated with an increased odds of developing hypertension.

Design.  —Case-control study of participants in the Veterans Administration (now Department of Veterans Affairs) Normative Aging Study, a 30-year longitudinal study of men.

Participants.  —Of 1171 active subjects who were seen between August 1991 and December 1994, 590 (50%) participated in this investigation and had data on all variables of interest.

Main Outcome Measures.  —Hypertension was defined as taking daily medication for the treatment of hypertension or systolic blood pressure higher than 160 mm Hg or diastolic blood pressure of 96 mm Hg or higher during the time of examination. Levels of lead in the tibia (representing cortical bone) and the patella (representing trabecular bone) were measured in vivo with a K x-ray fluorescence (KXRF) instrument. Levels of lead in blood were measured by graphite furnace atomic absorption spectroscopy.

Results.  —Blood lead levels were low, ranging from less than 0.05 to 1.35 μmol/L (<1 to 28 μg/dL), with a mean (SD) of 0.30 (0.20) μmol/L (6.3 [4.1] μg/dL). Bone lead levels were similar to those described in other general populations. In comparison to nonhypertensives, mean levels of lead in blood and both tibia and patella bone lead levels were significantly higher in hypertensive subjects. In a logistic regression model of hypertensive status that began with age, race, body mass index, family history of hypertension, history of ethanol ingestion, pack-years of smoking, dietary sodium intake, dietary calcium intake, blood lead, tibia lead, and patella lead, the variables that remained after backward elimination were body mass index, family history of hypertension, and level of lead in the tibia. An increase from the midpoint of the lowest quintile to the midpoint of the highest quintile of tibia lead from 8 to 37 μg per gram of bone mineral was associated with an increased odds ratio of hypertension of 1.5.

Conclusion.  —Our findings suggest that long-term lead accumulation, as reflected by levels of lead in bone, may be an independent risk factor for developing hypertension in men in the general population.(JAMA. 1996;275:1171-1176)

REFERENCES

1 +
Centers for Disease Control. Preventing Lead Poisoning in Young Children . Atlanta, Ga: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 1991;.
2 +
Kopp SJ, Barron JT, Tow JP.  Cardiovascular actions of lead and relationship to hypertension: a review. Environ Health Perspect . 1988;;78:91-99.
3 +
Pirkle JL, Schwarz 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.
4 +
Sharp DS, Becker CE, Smith AH.  Chronic low-level lead exposure: its role in the pathogenesis of hypertension. Med Toxicol . 1987;;2:210-232.
5 +
Hertz-Picciotto I, Croft J.  Review of the relation between blood lead and blood pressure. Epidemiol Rev . 1993;;15:352-373.
6 +
Landrigan PJ.  Strategies for epidemiologic studies of lead in bone in occupationally exposed populations. Environ Health Perspect . 1991;;91:81-86.
7 +
Rabinowitz M, Wetherhill G, Kopple J.  Kinetic analysis of lead metabolism in healthy humans. J Clin Invest . 1976;;58:260-270.
8 +
Manton WI.  Total contribution of airborne lead to blood lead. Br J Ind Med . 1985;;42:168-172.
9 +
Barry PSI, Mossman DB.  Lead concentrations in human tissues. Br J Ind Med . 1970;;27:339-351.
10 +
Schroeder HA, Tipton IH.  The human body burden of lead. Arch Environ Health . 1968;;17:965-978.
11 +
Saltzman BE, Gross SB, Yeager DW, Meiners BG, Bartside PS.  Total body burdens and tissue concentrations of lead, cadmium, copper, zinc and ash in 55 human cadavers. Environ Res . 1990;;52: 126-145.
12 +
Silbergeld EK.  Lead in bone: implications for toxicology during pregnancy and lactation. Environ Health Perspect . 1991;;91:63-70.
13 +
Rabinowitz MB.  Toxicokinetics of bone lead. Environ Health Perspect . 1991;;91:33-37.
14 +
Landrigan PJ, Todd AC.  Direct measurement of lead in bone: promising biomarker. JAMA . 1994;; 271:239-240.
15 +
Bell B, Rose CL, Damon A.  The Normative Aging Study: an interdisciplinary and longitudinal study of health and aging. Aging Hum Dev . 1972;; 3:4-17.
16 +
Ferris BG.  Epidemiologic standardization project. Am Rev Respir Dis . 1978;;118:1-120.
17 +
Willett WC, Sampson L, Browne ML, et al.  The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol . 1988;; 127:188-199.
18 +
Ward KD, Sparrow D, Vokonas PS, et al.  The relationships of abdominal obesity, hyperinsulinemia and saturated fat intake to serum lipid levels: the Normative Aging Study. Int J Obesity . 1994;;18: 137-144.
19 +
Burger D, Morsillo P, Adams B, Hu H, Milder FL.  Automated instrument for making K-x-ray fluorescence measurements in human bone. Basic Life Sci . 1990;;55:287-293.
20 +
Hu H, Milder F, Burger DE.  X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposures. Arch Environ Health . 1990;;45:335-341.
21 +
Hu H, Watanabe H, Payton M, Korrick S, Rotnitzky A.  The relationship between bone lead and hemoglobin. JAMA . 1994;;272:1512-1517.
22 +
Somervaille LJ, Chettle DR, Scott MC.  In vivo measurement of lead in bone using x-ray fluorescence. Phys Med Biol . 1985;;30:929-943.
23 +
Jones KW, Schidlovsky G, Williams FH, Wedeen RP, Batuman V.  In vivo determination of tibial lead by K x-ray fluorescence with a 109Cd source.  In: Ellis KJ, Yasumura S, Morgan WD, eds. In Vivo Body Composition Studies . London, England: Institute of Physical Sciences in Medicine; 1987;:363-373.
24 +
Gordon CL, Chettle DR, Webber CE.  An improved instrument for the in vivo detection of lead in bone. Br J Ind Med . 1993;;50:637-641.
25 +
Kim R, Aro A, Rotnitzky A, Amarasiriwadena C, Hu H.  K x-ray fluorescence measurements of bone lead concentration: the analysis of low-level data. Phys Med Biol . 1995;;40:1475-1485.
26 +
Rosner B.  Percentage points for a generalized ESD many-outlier procedure. Technometrics . 1983;; 25:165-172.
27 +
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.
28 +
Sharp DS, Benowitz NL, Osterloh JD, Becher CE, Smith AH, Syme SL.  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.
29 +
Grandjean P, Hollnagel H, Hedegaard L, Christensen JM, Larsen S.  Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders. Am J Epidemiol . 1989;;129:732-739.
30 +
Sharp DS.  Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders. Am J Epidemiol . 1990;;131:1098.
31 +
Schwartz J.  Lead, blood pressure, and cardiovascular disease in men. Arch Environ Health . 1995;; 50:31-37.
32 +
Batuman V, Landy E, Maesaka JK, Wedeen RP.  Contribution of lead to hypertension with renal impairment. N Engl J Med . 1983;;309:17-21.
33 +
Perry HM Jr, Erlanger MW, Perry EF.  Increase in the blood pressure of rats chronically fed low levels of lead. Environ Health Perspect . 1988;; 78:107-111.
34 +
Fine BP, Vetrano T, Skurnick J, et al.  Blood pressure elevation in young dogs during low level lead poisoning. Toxicol Appi Pharmacol . 1988;;93: 388-393.
35 +
Hu H, Milder F, Burger D.  X-ray fluorescence: issues surrounding the application of a new tool for measuring lead burden. Environ Res . 1989;;49:295-317.
36 +
Cochran WG.  Errors of measurement in statistics. Technometrics . 1968;;10:637-666.
37 +
Tyroler HA.  Epidemiology of hypertension as a public health problem: an overview as background for evaluation of blood lead-blood pressure relationship. Environ Health Perspect . 1988;;78:3-7.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Centers for Disease Control. Preventing Lead Poisoning in Young Children . Atlanta, Ga: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 1991;.
2 +
Kopp SJ, Barron JT, Tow JP.  Cardiovascular actions of lead and relationship to hypertension: a review. Environ Health Perspect . 1988;;78:91-99.
3 +
Pirkle JL, Schwarz 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.
4 +
Sharp DS, Becker CE, Smith AH.  Chronic low-level lead exposure: its role in the pathogenesis of hypertension. Med Toxicol . 1987;;2:210-232.
5 +
Hertz-Picciotto I, Croft J.  Review of the relation between blood lead and blood pressure. Epidemiol Rev . 1993;;15:352-373.
6 +
Landrigan PJ.  Strategies for epidemiologic studies of lead in bone in occupationally exposed populations. Environ Health Perspect . 1991;;91:81-86.
7 +
Rabinowitz M, Wetherhill G, Kopple J.  Kinetic analysis of lead metabolism in healthy humans. J Clin Invest . 1976;;58:260-270.
8 +
Manton WI.  Total contribution of airborne lead to blood lead. Br J Ind Med . 1985;;42:168-172.
9 +
Barry PSI, Mossman DB.  Lead concentrations in human tissues. Br J Ind Med . 1970;;27:339-351.
10 +
Schroeder HA, Tipton IH.  The human body burden of lead. Arch Environ Health . 1968;;17:965-978.
11 +
Saltzman BE, Gross SB, Yeager DW, Meiners BG, Bartside PS.  Total body burdens and tissue concentrations of lead, cadmium, copper, zinc and ash in 55 human cadavers. Environ Res . 1990;;52: 126-145.
12 +
Silbergeld EK.  Lead in bone: implications for toxicology during pregnancy and lactation. Environ Health Perspect . 1991;;91:63-70.
13 +
Rabinowitz MB.  Toxicokinetics of bone lead. Environ Health Perspect . 1991;;91:33-37.
14 +
Landrigan PJ, Todd AC.  Direct measurement of lead in bone: promising biomarker. JAMA . 1994;; 271:239-240.
15 +
Bell B, Rose CL, Damon A.  The Normative Aging Study: an interdisciplinary and longitudinal study of health and aging. Aging Hum Dev . 1972;; 3:4-17.
16 +
Ferris BG.  Epidemiologic standardization project. Am Rev Respir Dis . 1978;;118:1-120.
17 +
Willett WC, Sampson L, Browne ML, et al.  The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol . 1988;; 127:188-199.
18 +
Ward KD, Sparrow D, Vokonas PS, et al.  The relationships of abdominal obesity, hyperinsulinemia and saturated fat intake to serum lipid levels: the Normative Aging Study. Int J Obesity . 1994;;18: 137-144.
19 +
Burger D, Morsillo P, Adams B, Hu H, Milder FL.  Automated instrument for making K-x-ray fluorescence measurements in human bone. Basic Life Sci . 1990;;55:287-293.
20 +
Hu H, Milder F, Burger DE.  X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposures. Arch Environ Health . 1990;;45:335-341.
21 +
Hu H, Watanabe H, Payton M, Korrick S, Rotnitzky A.  The relationship between bone lead and hemoglobin. JAMA . 1994;;272:1512-1517.
22 +
Somervaille LJ, Chettle DR, Scott MC.  In vivo measurement of lead in bone using x-ray fluorescence. Phys Med Biol . 1985;;30:929-943.
23 +
Jones KW, Schidlovsky G, Williams FH, Wedeen RP, Batuman V.  In vivo determination of tibial lead by K x-ray fluorescence with a 109Cd source.  In: Ellis KJ, Yasumura S, Morgan WD, eds. In Vivo Body Composition Studies . London, England: Institute of Physical Sciences in Medicine; 1987;:363-373.
24 +
Gordon CL, Chettle DR, Webber CE.  An improved instrument for the in vivo detection of lead in bone. Br J Ind Med . 1993;;50:637-641.
25 +
Kim R, Aro A, Rotnitzky A, Amarasiriwadena C, Hu H.  K x-ray fluorescence measurements of bone lead concentration: the analysis of low-level data. Phys Med Biol . 1995;;40:1475-1485.
26 +
Rosner B.  Percentage points for a generalized ESD many-outlier procedure. Technometrics . 1983;; 25:165-172.
27 +
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.
28 +
Sharp DS, Benowitz NL, Osterloh JD, Becher CE, Smith AH, Syme SL.  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.
29 +
Grandjean P, Hollnagel H, Hedegaard L, Christensen JM, Larsen S.  Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders. Am J Epidemiol . 1989;;129:732-739.
30 +
Sharp DS.  Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders. Am J Epidemiol . 1990;;131:1098.
31 +
Schwartz J.  Lead, blood pressure, and cardiovascular disease in men. Arch Environ Health . 1995;; 50:31-37.
32 +
Batuman V, Landy E, Maesaka JK, Wedeen RP.  Contribution of lead to hypertension with renal impairment. N Engl J Med . 1983;;309:17-21.
33 +
Perry HM Jr, Erlanger MW, Perry EF.  Increase in the blood pressure of rats chronically fed low levels of lead. Environ Health Perspect . 1988;; 78:107-111.
34 +
Fine BP, Vetrano T, Skurnick J, et al.  Blood pressure elevation in young dogs during low level lead poisoning. Toxicol Appi Pharmacol . 1988;;93: 388-393.
35 +
Hu H, Milder F, Burger D.  X-ray fluorescence: issues surrounding the application of a new tool for measuring lead burden. Environ Res . 1989;;49:295-317.
36 +
Cochran WG.  Errors of measurement in statistics. Technometrics . 1968;;10:637-666.
37 +
Tyroler HA.  Epidemiology of hypertension as a public health problem: an overview as background for evaluation of blood lead-blood pressure relationship. Environ Health Perspect . 1988;;78:3-7.

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