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The Normative Aging Study

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

JAMA. 1996;275(15):1171-1176.

Abstract
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)

Author Affiliations
From the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School (Drs Hu, Aro, Payton, Korrick, and Weiss); Occupational Health Program, Department of Environmental Health (Drs Hu, Aro, and Korrick), and Department of Biostatistics (Dr Rotnitzky), Harvard School of Public Health; and the Veterans Administration (now Department of Veterans Affairs) Normative Aging Study (Dr Sparrow), Boston, Mass.

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

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