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

AX6-156
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
Asia (cont’d)
Lee et al. (2001)
(cont’d)
Lustberg et al.
(2004)
Korea-Chonan
1997-1999 (period
of enrollment; no
statement on dates
of data collection)
Logistic regression analysis was used to test
the effect of the Pb indices on hypertension
(systolic >160 mm Hg or diastolic
>96 mm Hg or taking antihypertensive
medications) using the same group of
potential covariates, testing the Pb terms
and the Pb-genotype interaction terms
separately. The hypertension models tested
both gene polymorphisms separately.
793 (number given for genotype analysis;
numbers in models not given) current and
former Pb workers, mean (SD) age 40 (10)
yrs and 80% male, were genotyped for the
three polymorphisms of endothelial nitric
oxide synthase (eNOS) (GG, GT, TT), an
enzyme that is a modulator of vascular
resistance. The effect of genotype and the
interaction of genotype with blood Pb and
tibia Pb on systolic and diastolic blood
pressure were evaluated by multiple linear
regression analyses, forcing covariates of
age (modeled as a 2 degree of freedom
spline with knot at 45 yrs), sex, natural log
BMI, smoking and alcohol consumption,
high school education, and job duration.
Both blood Pb and tibia Pb were entered as
percentiles and entered together. Logistic
models of hypertension (systolic
∃140 mm Hg or diastolic ∃90 mm Hg or
reported use of antihypertensive
medication) used the same covariates.
Interaction terms between each of the Pb
measures (plus a Pb-squared term) and
genotype was used to determine differential
effect of Pb according to genotype.
Pb according to
genotype:
Arithmetic mean
(SD) blood Pb, GG:
32 (15) µg/dL
Arithmetic mean
(SD) blood Pb,
TG/TT: 32
(15) µg/dL
Mean (SD) tibia Pb,
GG: 37 (42) µg/g
Mean (SD) tibia Pb,
TC/TT: 36 (34) µg/g
Subjects with the Bb/BB genotypes had a significantly higher odds hypertension
prevalence (OR = 2.1 [95% CI: 1.0, 4.4]) than subjects with the bb genotype,
adjusting for age, sex, BMI, tibia Pb, and current alcohol use. There were no
significant effects of any Pb variable nor of ALAD on hypertension status.
Linear blood Pb may not give efficient and unbiased estimates of blood Pb effect on
blood pressure. The descriptive data shows highly skewed distributions for blood Pb,
DMSA-chelatable Pb, and tibia Pb in this group, suggesting that coefficients of all Pb
effect on blood pressure may not have been efficient and unbiased. Stepwise models
usually produce different covariate patterns for different models, though the tables
indicate that the covariates used for all the models discussed above were the same. No
model diagnostic tests were reported.
85% (673/793) of the group were typed GG, 14% (114/793) were TG, and 1% (6/793)
were TT. TG and TT groups were combined for analysis (TG/TT).
Mean systolic and diastolic blood pressures, adjusted for all covariates, were not
significantly different between GG and TG/TT groups.
In multiple regression models for systolic and diastolic blood pressure, neither
percentile blood Pb nor percentile tibia Pb, entered together, were significant
predictors. Interaction terms between the Pb variables and genotype were not
significant.
In the logistic regression model for hypertension, neither percentile blood Pb nor
percentile tibia Pb, entered together, were significant predictors.
Reporting was incomplete: number of subjects entering the models was not stated; no
comparisons between recruited subjects and subjects not used in models. Despite
reporting non-significant interactions, the paper showed both loess plots and tables of
analyses stratified by genotype, reporting significant associations between both tibia
and blood Pb in the GG genotype, insignificant in the other. Inspection of the loess
plots revealed striking non-linearity for both adjusted blood Pb-systolic blood pressure
and adjusted tibia Pb-systolic blood pressure relationships. Small group size of the
TG/TT genotypes and highly unbalanced terms of the interaction may have
contributed to the non-significant interactions. Although the interaction Pb term was
also probed as a quadratic function, the tibia Pb interaction was not, suggesting that
poor concentration-response specification in the model may also have contributed to
the lack of significant main effects and interactions.