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

AX6-166
Table AX6-5.4. Cardiovascular Effects of Lead on Children
Reference, Study
Location, and Period Study Description Pb Measurement Findings, Interpretation
United States
Chen et al. (2006)
U.S.-Baltimore, MD;
Cincinnati, OH;
Newark, NJ;
Philadelphia, PA
~1998-2004
780 children from 12-33 mos participated
in a randomized clinical trial of oral
succimer chelation in four clinical
centers. Half the children had up to three
26-day treatments, the other half were
given placebo. 75% got two treatment
sessions and 81% of those with two
treatments received a third.
Blood pressure was measured pretreatment,
at 7, 28, and 42 days after each
treatment, then every 3 to 4 mos for five
yrs of follow up. Cross-sectional
multiple regression models adjusting for
clinic location, baseline linear Pb, race,
sex, parents’ education, single parent, age
at test, height at test, and BMI at test for
each period of the study tested the
difference of diastolic and systolic blood
pressure between placebo and succimer
groups. Cross-sectional multiple
regression models for the effect of linear
blood Pb at each period on blood
pressure adjusted for clinic location,
treatment group, race, sex, parents’
education, single parent, age at test,
height and BMI. Two mixed models,
one from start of treatment to 9-mo
follow up, the other from 12 to 60 mos
follow up, adjusted for the same
variables, and tested the effect of
treatment group over time.
Blood Pb ranged from
20-44 µg/dL at pre-treatment
and from 1-27 µg/dL at 5 yr
follow up. Succimer-treated
group had significantly
lower blood Pb than placebo
group only for 9-10 mos
following the end of
treatment. Blood Pb did not
differ significantly beyond
that period.
Adjusted systolic blood pressure was significantly higher in the succimer
group than the placebo group at 36 mos (1.27 mm Hg [95% CI: 0.06,
2.48]) and at 60 mos follow up (1.69 mm Hg [95% CI: 0.34, 3.04]).
Systolic blood pressure was not significantly different at any other time
period; diastolic blood pressure was never significantly different between
groups.
Concurrent linear blood Pb was not associated with blood pressure in
cross-sectional models at any time point in the study. Adjusted
coefficients for linear blood Pb and systolic blood pressure ranged from
1.36 mm Hg (95% CI: !0.58, 3.30) at pre-treatment to !0.72 mm Hg (95%
CI: !1.91, 0.48) at 36 mos of follow up. Diastolic pressure coefficients
were generally lower but followed the same pattern.
Mixed model analysis for start of treatment through 9 mos follow up
showed succimer treatment effect of 0.24 mm Hg (95% CI: !0.79, 1.28)
for systolic and 0.46 mm Hg (95% CI: !0.44, 1.36) for diastolic blood
pressure. The treatment effect from 12 through 60 mos follow up was
1.09 mm Hg (95% CI: 0.27, 1.90) systolic and 0.15 mm Hg (95% CI:
!0.45, 0.75) for diastolic blood pressure.
The only reliable effect of succimer treatment was an elevation of systolic
blood pressure, especially notable between three and five yrs post
treatment. The authors could not account for the apparent increase in
blood pressure in the succimer-treated group 3-5 yrs after treatment ended.
It is notable that the two groups had different mean blood Pb for less than
a yr after succimer treatment ended, a period perhaps too short to observe
any beneficial effect of treatment. Failure to find cross-sectional effects of
blood Pb on blood pressure, especially pre-treatment, may indicate that Pb
exposure for a period of less than three yrs after birth is not sufficient to
affect blood pressure or that blood pressure measurements in the first three
yrs of life are highly variable, as could be seen from scatter plots of blood
pressure vs. blood Pb at pre-treatment compared 60 mo follow up. The
use of linear Pb term may have reduced sensitivity to finding a significant
blood Pb effect on blood pressure. No model diagnostics mentioned.