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

AX6-134
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)
Glenn et al.
(2001)
U.S.-New Jersey
1996-1997
213 males (92% white), mean (SD)
age 58.0 (7.4) yrs, working or
formerly working at a plant
producing tetraethyl or tetramethyl
Pb until 1991, were genotyped for
ATP1A2(5’) and ATP1A2(3’)
polymorphism. ATPase is thought to
play a role in regulating blood
pressure and Pb inhibits its activity.
Blood pressure, blood Pb, and tibia
Pb were measured. Multiple linear
regression models were used for
systolic and diastolic blood pressure.
Logistic regression model was
reported for hypertension
(systolic >160 mm Hg,
diastolic > 96 mm Hg, or taking
antihypertensive medications).
Covariate entry methods not
specified, but were likely stepwise.
Covariates for the blood pressure
model were age, use of
antihypertensive medications,
alcohol, smoking, season of yr, linear
blood Pb, tibia Pb (the two Pb
measures apparently tested
separately), ATP1A2(5’) and
ATP1A2(3’) polymorphism (each
tested separately), and an interaction
term between polymorphism and Pb.
Covariates for the hypertension
models were age, BMI, lifetime
alcoholic drinks, linear blood Pb and
tibia Pb, and polymorphism, each Pb
measure and polymorphism tested
separately.
Arithmetic mean (SD, range)
blood Pb:
5.2 µg/dL (3.1, 1-20)
Mean (SD) tibia Pb:
16.3 µg/g (9.3)
None of the relationships between the ATP1A2(5’) polymorphism and either blood
or bone Pb or blood pressure were significant.
The ATP1A2(3’) polymorphism was homogenous for the 10.5 kilobase allele
(10.5/10.5) in 11 subjects, heterogeneous for the 10.5 and 4.3 kilobase allele
(10.5/4.3) in 82 subjects, and heterogeneous (10.5/4.3) in 116 subjects. Prevalence
of the 10.5 allele was significantly higher in blacks than in whites.
Regression coefficients of 4.3/4.3 and 10.5/4.3 genotypes were not significantly
different and all subsequent analyses compared the 10.5/10.5 genotype with the
combined 4.3/4.3-10.5/4.3) genotype. The significant interaction between linear
blood Pb and the 10.5/10.5 genotype showed that for every 1 µg/dL of blood Pb
systolic blood pressure increased 5.6 mm Hg (95% CI: 1.2, 9.9) more than the blood
pressure of the combined genotype group. Blood Pb range of the combined
genotype group was twice that of the 10.5/10.5 group. When data were truncated to
make blood Pb of both groups cover the same range, coefficients of the genotypelinear
blood Pb interaction term did not change appreciably. Authors state that tibia
Pb interacted with genotype on blood pressure but showed no data to estimate either
type or size of effect. Diastolic blood pressure was not related to genotype, to Pb or
to the interaction between Pb and genotype.
Prevalence of hypertension (30% in total sample) was significantly higher among
the 10.5/10.5 group (63.4 %) than among the combined group (28.3 %). Adjusting
for age, BMI, and lifetime alcohol, the odds of hypertension in the 10.5/10.5 group
were OR = 7.7 (95% CI: 1.9, 31.4) compared to the 4.3/4.3 group. The
heterogeneous group was not significantly different from the 4.3/4.3 group.
Linear blood Pb specification not indicated for blood Pb-blood pressure modeling.
Examination of partial residual plot for systolic blood pressure and linear blood Pb
shows typical heterogeneity of residuals as a function of predicted values. Thus,
presented coefficients may be inefficient and biased. Only 9 subjects were
homogenous for 10.5/10.5 in the multiple regression model. Only cortical bone Pb
was tested, not trabecular bone Pb. Cortical bone Pb models not shown or
quantitatively described. Blood Pb rounded to nearest unit µg/dL. Mixed organicinorganic
Pb exposure. Relatively small sample size may have prevented detection
of other significant effects. No model diagnostics described.