Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX6-140
Table AX6-5.1 (cont’d). Effects of Lead on Blood Pressure and Hypertension
Reference, Study
Location, and
Period Study Description Pb Measurement Findings, Interpretation
United States (cont’d)
Schwartz et al.
(2000c)
U.S.-Eastern
1996-1997
543 mostly former organolead
workers, predominantly white
(92.8%), at a tetraethyl/tetramethyl
plant, mean (SD) [range] age 7.6 (7.6)
[41.7-73.7] yrs had blood Pb, DMSAchelatable
Pb (4-hr. urinary Pb
excretion after a single 10 mg/kg dose
of DMSA) measured for modeling
systolic and diastolic blood pressure
and hypertension (systolic >160
mm Hg or diastolic ∃96 mm Hg or
taking antihypertensive medications.
Tibia Pb ~2 yrs later was also used as
a Pb index. For blood pressure, linear
multiple regression with backward
elimination of non-significant
covariates or covariates that “had
important influence on the coefficients
for the Pb-dose terms.” Each Pb
variable was tested in a separate
model. Potential covariates for these
models were age, BMI, current
tobacco use, and current use of
antihypertensive medications. Other
models were constructed taking out
those subjects using antihypertensive
medications. Both linear and linear +
quadratic blood and tibia Pb terms
were tested. Logistic regression
analyses were used to test the effect of
the Pb variables on hypertension,
controlling for age, diabetes, lifetime
alcohol consumption, and BMI.
Logistic models also tested each Pb
measure in interaction with age.
Blood Pb arithmetic
mean (SD, range):
4.6 µg/dL (2.6, 1
to 20)
DMSA-chelatable Pb
mean (SD, range):
19.0 µg (16.6, 1.2
to 136)
Tibia Pb mean (SD,
range): 14.4 µg/g
(9.3, !1.6 to 52)
Adjusting for age, BMI, current smoking, and current use of antihypertensive medications,
each 1 µg/dL increase in blood Pb-squared was significantly associated with 0.189 mm Hg
(95% CI: 0.087, 0.330) increase in systolic blood pressure with three outliers removed.
With the same covariates, each 1 µg/dL increase in linear blood Pb was significantly
associated with 0.310 mm Hg (95% CI: 0.028, 0.592) in diastolic blood pressure taken
over a 2-yr period (n = 525). No other Pb variables were significant.
For the hypertension models, only the interaction of linear blood Pb by age was significant,
with subjects showing significant decrease in odds ratio of hypertension with every joint
increase of 1 µg/dL blood Pb and 1 yr increase in age (linear blood Pb X age OR = 0.98;
[95% CI: 0.97, 0.99]). The interaction suggested a concentration-response relationship
between linear blood Pb and hypertension only up to ~58 yrs of age.
Authors note that blood pressure findings “were not affected by exclusion or inclusion of
subjects using antihypertensive medications,” but do not present either the data or the
statistical tests to evaluate that conclusion. No other model diagnostics were reported.
Although blood Pb was also modeled as a quadratic Pb term for systolic blood pressure, no
analysis was shown for non-linear blood Pb terms for diastolic blood pressure.
Trabecular bone Pb was not tested, though other studies indicate that it is a better Pb index
than cortical Pb for cross-sectional blood pressure and hypertension study.
Although the backward procedures described could have resulted in less than the full set of
considered covariates entering the models, all model presentations were limited to showing
the Pb coefficients and all models indicated in a footnote that the Pb coefficients were
adjusted for each possible covariate for that model. While this is possible with the short
list of covariates, given the 14 models presented one might expect to see at least one model
where one of the covariates did not remain.