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

AX6-153
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
Europe (cont’d)
Staessen et al.
(1996a) (cont’d)
Staessen et al.
(1993)
Belgium-Cadmibel
Study
1985-1989
For the hypertension incidence model two
definitions of hypertension were used:
definite hypertension (systolic >160 mm Hg,
diastolic >95 mm Hg or taking
antihypertensive medications) and borderline
hypertension (systolic between 141 to
159 mm Hg and diastolic between 91 to
94 mm Hg). Method of covariate entry into
hypertension incidence models not stated.
Baseline natural log blood Pb was used as the
exposure index.
827 males and 821 females recruited from two
areas in Belgium, one of them surrounding a
non-ferrous smelter, mean age (SD) 46 (15)
and 44 (15) yrs, in men and women
respectively. Subjects taking antihypertensive
medication were excluded from the analyses.
Stepwise multiple regression models of
systolic and diastolic blood pressure were
stratified by sex. Covariates available for
entry were age and age-squared, BMI, pulse
rate, log protoporphyrin, log gammaglutamyltranspeptidase,
serum calcium, log
serum ferritin, log serum creatinine, log serum
zinc, urinary calcium, urinary sodium, and
urinary potassium. Natural log blood Pb was
the only variable forced into the models.
Additional models tested the interaction of
serum calcium and blood Pb on blood
pressure.
Geometric mean
blood Pb (range),
stratified by sex:
Male blood Pb:
10.4 µg/dL
(2.7, 84.9)
Female blood Pb:
6.2 µg/dL (1.3, 42.4)
The over six decades of age represented in the sample was modeled by linear and
quadratic terms based on age quintiles rather than continuous age, making it likely
that adequate control for age effects on blood pressure was not achieved and that
the “healthy subject” effect seen in older groups was not controlled. If stepwise
addition of significant covariates was used in the blood pressure difference models,
were covariates in those models that were marked in the coefficient column as
non-significant not included in the models, and if that were so, it is unclear from
where the probability values that substitute for the coefficients of those variables
were derived. There were no model diagnostic tests reported.
In men, adjusting for age and age-squared, BMI, pulse rate, log gammaglutamyltranspeptidase,
serum calcium, and log serum creatinine, every unit
natural log blood Pb increase was significantly associated with a -5.2 mm Hg (95%
CI: !0.5, !9.9) decrease in systolic blood pressure. Natural log blood Pb was not
significant in the model for diastolic blood pressure for men nor the systolic or
diastolic blood pressure for women.
Adjusting for age and age-squared, BMI, pulse rate, and log gammaglutamyltranspeptidase,
the interaction term between natural log blood Pb and
serum calcium was only significant for systolic blood pressure in women. Every
doubling of blood Pb was associated with a 1.0 mm Hg decrease in systolic blood
pressure at serum calcium concentration of 2.31 mmol/L (25th percentile) and an
increase in systolic blood pressure of 1.5 mm Hg at serum calcium concentration
of 2.42 mmol/L (75th percentile).
Stepwise multiple regression analyses run risks of accepting chance associations
due to multiple analyses of the same data set. The role of alcohol use or alcohol
use markers in confounding Pb effect on blood pressure in this setting has already
been noted. The unexplained interaction between serum calcium and blood Pb
highlights the potential confounding role of serum calcium with Pb in blood
pressure studies. The study shows graphs indicating distinct differences in the ageserum
calcium and age-blood Pb relationships for men and women. From 50-70
yrs of age serum calcium is higher than from ≤ 29-49 yrs in women and