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### Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES III Mortality Study Author(s): Susan E. Schober, Lisa B. Mirel, Barry I. Graubard, Debra J. Brody and Katherine M. Flegal Source: Environmental Health Perspectives, Vol. 114, No. 10 (Oct., 2006), pp. 1538-1541 Published by: The National Institute of Environmental Health Sciences (NIEHS) Stable URL: http://www.jstor.org/stable/3838177 Accessed: 28-09-2015 14:38 UTC

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# Research

Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES Ill Mortality Study

Susan E. Schober,1 Lisa B. Mirel,2 * Barry L Graubard,3 Debra J. Brody,' and Katherine M. Flegal1

1Division of Health and Nutrition Examination Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland, USA; 2Harris Corporation, Falls Church, Virginia, USA; 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA

BACKGROUND: Analyses of mortality data for participants examined in 1976-1980 in the second National Health and Nutrition Examination Survey (NHANES II) suggested an increased risk of mortality at blood lead levels > 20 pgIdL. Blood lead levels have decreased markedly since the late 1970s. In NHANES III, conducted during 1988-1994, few adults had levels > 20 ,ug/dL.
OBJECTIvE:

Our objective in this study was to determine the risk of mortality in relation to lower blood lead levels observed for adult participantsof NHANES III.

METHODS: We analyzedmortality information for 9,757 participants who had a blood lead measurement and who were 2 40 years of age at the baseline examination. Using blood lead levels categorized as < 5, 5 to < 10, and 2 10 pg/dL, we determined the relative risk of mortality from all causes, cancer, and cardiovascular disease through Cox proportionalhazard regression

analysis.

RESULTS:

Using blood lead levels < 5 pg/dL as the referent, we determined that the relative risk of mortality from all causes was 1.24 [95% confidence interval (CI), 1.05-1.48] for those with blood levels of 5-9 pg/dL and 1.59 (95% CI, 1.28-1.98) for those with blood levels 2 10 ,g/dL (p for trend < 0.001). The magnitude of risk was similar for deaths due to cardiovascular disease and cancer, and tests for trend were statistically significant (p < 0.01) for both causes of death.

CONCLUSION: In a nationally representative sample of the U.S. population, blood lead levels as low

as 5-9 pg/dL were associatedwith an increased risk of death from all causes, cardiovascular disease, and cancer.

KEY WORDS: cancer, cardiovascular disease, lead, mortality, National Health and Nutrition Examination Survey (NHANES), United States. Environ Health Perspect 114:1538-1541 (2006). doi:10. 1289/ehp.9123 available via http.//dx.doi.orgl [Online 6 July 2006]

Toxic effects

of exposure

to high levelsof lead among adults in occupational settings and from poisoningsinclude neurologic and renal impairmentas well as effects on other organ systems [Agency for Toxic Substances and Disease Registry (ATSDR) 1999]. Environmental exposure to lead-exposure much lower than that found in occupational settings-is associated with long-term adverse effects,particularly

on blood pressure

(Cheng et al. 2001; Glenn et al. 2003; Hertz-Picciotto and Croft 1992; Hu et al. 1996; Moller and Kristensen 1992; Nash et al. 2003), renal function (Kim et al. 1996; Muntner et al. 2003; Paytonet al. 1994; Staessen et al. 1992; Tsaih et al. 2004), and cognition (Payton et al. 1998; Weisskopf et al. 2004; Wright et al. 2003). Recent reports suggestthat even blood lead levels that are currently typical in the U.S. population are associated with renal dysfunction (Muntner et al. 2005) and peripheral arterial disease (Muntner et al. 2005; Navas-Acien

et al. 2004). Leadand lead compounds are reasonably anticipated to be human carcinogens based on evidence from occupational mortality and animal studies [National ToxicologyProgram

(NTP) 2005]. Lead exposure declined dramatically beginningin the late 1970s largely because of mandated

removal of lead from gasoline,

from paint, and to a lesser

extent, from solderused in cans (Annest

et al. 1983; Pirkle

et al. 1994). Blood lead measurements from the National Health and Nutrition Examination Surveys (NHANES) have provideddocumentation of leadexposure

in the U.S. population

beginning with datafromNHANES II conducted during 1976-1980. Among person 1-74 years of age, the geometric

mean of blood lead

level dropped from 12.8 pg/dL in 1976-1980 to 2.8 ,ug/dL in 1988-1991 (Annest et al. 1983), and to 2.3 pg/dL in 1991-1994 [Centers for Disease Control and Prevention

(CDC) 1997]. Analyses of mortality follow-up data for participants of NHANES II suggested an increased riskof mortality

at blood lead levels
> 20 pg/dL Uemal et al. 2002; Lustberg and Silbergeld

2002). Mortality

follow-up

through the year 2000 is now available for NHANES III participants.

The purpose

of our studywas to examine the risk of mortality from all causes, cardiovascular

disease, and cancer in relation to blood lead levelsobserved for adult participants

of NHANES III. 

## Methods
NHANES III was fielded in two phases, the first from 1988 through October 1991 and the second from November 1991 through 1994. The survey consisted of a household interviewand a standardized physicalexamination in a mobile examination center. The NHANES III samplewas selected through a complex, multistage probabilitydesign. The 

### survey hasbeendescribed

in detail elsewhere (CDC 1994). During the physical

examination,

blood
wasobtained

by venipuncture

for all survey participants

? 1 year of age.Blood

leadconcentrations

were measured bygraphite

furnace atomicabsorption

spectrophotometry

and expressed in micrograms

per deciliter. Details regarding laboratory methods and qualitycontrol procedures

have been described previously (Pirkle t al. 1994). NHANES

III participants

? 17 years

of age were eligible forpassive

mortalityfollowup, which has been completed for deaths occurring through December 2000.Mortality information

is based on theresults

of a probabilistic match between NHANES

IIIandthe National Death Index records [National Center for Health Statistics (NCHS) 2006]. This analysis was limited to persons ? 40 years of ageat the time

of the examination.Of the 10,202

persons ? 40 years of age, 9,762 (95.7%) had a blood leadmeasurement at baseline.

Five persons were excluded because of insufficient

information

to allow for follow-up, resulting in a sample of 9,757 persons.

The median

length of followup was8.55 years,

during which there were 2,515 deaths(25.8%of participants). The International

Classification

of Diseases,

Tenth 

### Revision (ICD-10; NCHS 2006)wasused

to identify deaths due to malignant

neoplasm (ICD-10 codes COO-C97)

and majorcardiovascular disease(ICD-10 codes 100-178). Persons who were not matched

to a death record were considered

alive throughthe

Addresscorrespondence to S. Schober,NHANES Program,

NCHS, CDC, 3311 Toledo Rd., Room 4210, Hyattsville, MD 20782 USA. Telephone: (301) 458-4484. Fax: (301) 458-4028. E-mail: SSchober@cdc.gov *Current address: Government Accountability Office,Washington,

DC. This research was supported in part by the Intramural

Research Program of the Department

of Health and Human Services, National Institutesof Health,NationalCancer

Institute. The findings and conclusions in this article are those of the authors

and do not necessarily

represent the views of the Centers for Disease Control and Prevention

or the Government

Accountability

Office. At the time this research was conducted, L.B.M.

was an employee of Harris Corporation working under contract for the CDC/NCHS. The other authors declare they have no competing financial interests. Received 24 February

2006; accepted

5 July2006.



### 1538 VOLUME 1141 NUMBER 10 1October 2006 * Environmental

Health Perspectives

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### Blood lead levels and mortality risk,NHANES

IIl

follow-up period and administratively

censored 31 December

2000. Blood lead levels were categorized

as < 

### 5, 5 to < 10, and ? 10 pg/dL. The sample

size forpersons

withblood

lead levels ? 20 ,ug/dL
wastoo small

to provide

reliable estimates of mortality risk for this group.

Because of the skewed distribution

of blood leadconcentrations, log-transformed

values wereusedfor additional analyses using lead levels as a continuous variable. A participant's

agewas defined

as his or her agein years

at the baseline

examination. Race/ethnicity was categorized as nonHispanic white, non-Hispanic

black, Mexican American, and other. Education level wascategorized as < 12 years

or ? 12 years

of education. Total family income was defined as < $20,000/year

or 2 $20,000/year.

Region, as defined by the U.S. Census

Bureau (2006),
was recorded asNortheast,

Midwest, West, or South. Urban status of residence

wasdefined by population

size and place of residence,

and categorized

into two groups:

central or fringe counties of metropolitan

areas with population sizeof ? 1 million

versus all other areas. History of cigarette

smoking wascategorized
as never,former,

or current.

Alcohol consumption wasusedas a continuous

variable and defined by summing the number of drinks of beer, wine,or liquor

consumed per week. More than 21 drinks was truncated and counted as21. We used Coxproportional

hazardregression analysis,

usingage as the time scaleto examine therelative

hazard (or relative risk) of mortality from all causes, cancer, andcardiovascular disease using categories of blood lead concentrations

a described

above (Korn et al. 1997). As recommended by Korn et al. (1997), we stratified

the baseline

hazard by birthcohort;

we used 6-year

intervals. This controls for potential

cohortdifferences

in cumulative

exposure to leadbefore

the late 1 970s, when current exposure to lead began to decline dramatically

(Annest et al. 1983; Pirkle et al. 1994). Bloodleadlevels largely reflectcurrent

exposure (Rabinowitz

et al. 1976) and are an imperfect

measure of a person'slifetime

exposure to lead. Becausecurrent lead exposureand blood lead levels continued to decline over the 6-year period of blood collection

in NHANES (CDC 1997; Pirkle et al. 1994),

we also stratified the baselinehazard

by survey phase. For cause-specific analyses, follow-up for those who diedfrom other causes was censored attheage ofdeath. Initial models assessed univariateassociations of covariates and mortality. Next, we constructedmultivariate proportional

hazard models to examine the association of lead exposure and mortality after adjusting for potential confounders. All two-way interactions with blood lead category

were assessed. 

### We assessed the proportional

hazardassumptionby examining

the consistency

of the relative hazards

of mortalityacrossthree age groups. We defined three age categories, 40-74, 75-84, and ? 85 years, so thatthere
were anapproximately

equal number of deaths from allcauses in each category. Study subjects
can be induded

in more than oneage group as their ages change during thefollow-up

period. Because the cancer

mortality andbloodlead relationship

was different formenand

women in a previous

study of theNHANES

II cohort,
we also stratified multivariate

models separately for males and females. We analyzed

the dose-response

relationship of blood lead andmortality

in twoways. First, the multivariate-adjusted

relative risks
across the threeblood lead categories were tested for trend. A linear term consisting

of the median

values for eachlead group

was placedin the proportional hazards model instead of the dummy variablesfor each group, and this linear term was analyzed using a Wald test.Second,

the dose-response relationship

between lead andmortality

from allcauses was evaluated using log-transformed blood lead concentration

asa continuous

variable with a five-knot

cubic regression spline in the multivariate

proportional

hazards model (Durrleman

and Simon 1989). We used a Wald test to evaluate the dose-response relationship. Statistical analyses were conducted

using the SASSystem

for Windows (release

9.1; SAS Institute Inc., Cary,

NC) andSUDAAN (release 9.0; Research

Triangle Institute, Research Triangle Park, NC). All analyses included sample weights that accounted

for the unequal

probabilities

of selection and nonresponse.

All variance

calculations

incorporated thesample

weights and accounted for thecomplex

sample design using Taylor series linearization.

All significance

tests weretwosided using p < 0.05 as the level

of statistical significance. 

### Results Table 1 summarizes

characteristics

of the NHANES

IIIcohort by blood lead categories. Person-years

of follow up were approximately 53,000, 20,000, and 4,500byblood

leadcategories < 

### 5, 5-9, and? 10 1ig/dL,

respectively. Remaining

estimates are weighted by thesample weights.

Blood leadlevels

increased with age. Bloodleadconcentrations weredisproportionately

higher for men, non-Hispanic blacks, those with low income, those with educational

attainment

of < 12 years,

current smokers, andresidents

of the Northeast,

and persons who participated

in the first

phase of the survey.

Alcohol intake was positivelyassociated withblood

lead concentrations.

No differences in blood lead concentrations

byurban status of residences

were noted. The number

of deaths and multivariateadjusted relative risks of mortality

due to all causes, cardiovascular

disease, andcancer

by blood lead category are presented in Table 2. The multivariate

results exclude 71 persons with missing

information

on education

level, for a final sample

size of 9,686. Afterthis exclusion, there were a totalof 2,485 deaths from all causes, 1,189 from cardiovascular disease, and 543 from

cancer. Foreachcategory of deaths, statistical testing did not support the null hypothesis

that proportional

Table 1. Characteristics

of the study cohort by bloodlead level.
Blood leadlevel (pg/dL) Characteristic < 5 5-9 > 10 Sample size 6,608 2,532 617 Person-years 53,398 19,939 4,509 Median blood leadlevel(pg/dL) 2.6 6.3 11.8 Mean age at baseline

(years) 57.0 60.6 62.0 Male (%) 39.1 65.2 74.2 Race/ethnicity

(%) Non-Hispanic

white 82.7 78.1 65.7 Non-Hispanic

black 7.4 12.3 22.6 Mexican-American 3.4 3.5 4.3 Other 6.5 6.1 7.5 Total family income < $20,000 (%) 29.8 41.2 52.3 Education level < 12 years (%) 26.2 39.0 50.8 Smoking status at baseline

(%) Never 48.1 26.1 19.3 Former 33.8 39.0 36.5 Current 18.1 34.9 44.2 Mean alcohol intake (drinks/week) 2.0 4.6 5.5 Census region (%) Northeast 17.4 29.1 36.2 Midwest 25.1 25.2 17.8 South 36.3 27.8 31.7 West 21.2 18.0 14.3 Urban status (%) 45.6 52.1 51.3 Phase 1 of survey

(%) 44.4 58.2 65.3

Environmental

Health Perspectives * VOLUME 114 1 NUMBER

10 1 October

2006 1539

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All use subject to JSTOR Terms and ConditionsSchober et at.

hazardswere constant by age, although the lead-mortality relationships were generally consistent

across age strata.

For completeness, age-stratified

resultsare shown in addition to resultsfor all ages combined. The following covariateswere included in all multivariate models: sex, race/ethnicity, education level, and smokingstatus.Census regionand urban status of residence were not predictive, and alcohol intake was weakly predictiveof mortality in our analysis. Including these three covariates in the analysis did not alter the blood lead and mortality relationships;

therefore, we excludedthese three covariates from the final multivariate

models. Socioeconomic status, as indicated by either annual family income (categorized as < $20,000 and ? $20,000) or educationlevel was an important confounderin the multivariate analyses. We chose to use education level ratherthan income in our final models because therewas less missing information for this variable.In general, interaction terms between lead and covariates were not statistically

significant.

We found a p-value of 0.02 for the interaction terms lead x education in the cardiovascular disease model and lead x race/ethnicity in the

cancer mortality model; however, the interactive effectswere not largeand did not alter the direction of the lead-mortality relationships. Therefore, we did not include these terms in our finalmodels. In general,we found an increased risk of mortality from all causes

with increasing

blood lead levels (Table2), wherethe referencecategory was blood lead levels < 5 ,ug/dL. For all ages combined, the relative risksof mortality

were 1.24 [95% confidence interval (CI), 1.05-1.48) for those with blood levels of 5-9 pg/dL and 1.59 (95% CI, 1.28-1.98) for those with blood levelsof ? 10 pg/dL (testfor trend, p < 0.001). For mortality due to cardiovascular disease, there was also a pattern of increasing

riskwith increasing

blood lead. For all agescombined,

the estimated

relative risk of mortality

from cardiovascular

disease was 1.20 (95% CI, 0.93-1.55) for thosewith blood lead levels of 5-9 ,ug/dL and 1.55 (95% CI, 1.16-2.07) for those with blood lead levels of ? 10 1g/dL (test for trend,p < 0.01). For all ages combined, the estimated relativerisk of mortality from cancer was 1.44 (95% CI, 1.12-1.86) for those with blood lead levelsof 5-9 ,ug/dL

and 1.69 (95% CI, 1.14-2.52) for thosewith blood leadlevels of ? 10 pg/dL (test for trend, p < 0.01). We further explored the dose-response relationship

between blood lead concentrations and mortality

from all causes

by modelingthe proportional hazardsusing log-transformed blood lead levels on a continuousscalewith a five-knot cubic regression spline. The spline analysis results displayed as relative hazards using a referent

blood lead level of 1.5 ,ug/dL (12.5th percentile) and 95% CIs are shown graphically

in Figure 1. This resultis adjusted for all covariates

included in the final model shown in Table 2. The lower bound of the 95% CI of the relative

hazard exceeds unity at

a blood lead concentrationof approximately 5.5 ,ug/dL.

The relative

hazard remains < 2 for blood leadlevels

< 10 ,ug/dL. 

### Discussion
In this analysis of mortality among a large cohort of adults representative of the U.S. population, we found an increased risk of death from all causes, cardiovascular disease, and cancer

associated

with elevated

blood lead levels. Overall,the increase in risk was small; however,the increase

was observed

for blood lead levels as low as 5-9 1g/dL. Our finding of dose-response relationships between mortality risk and increasing blood lead levels for all three classes

of death strengthens

the conclusion that blood lead levels are associated with an increased

riskof mortality. Previousresearch

has examinedmortality riskand blood lead levelsin the generalpopulation of the United States using mortality follow-up data for participants 30-74 years of age from NHANES II, a study with baseline data collected during 1976-1980 and follow-up through 1992 (emal et al. 2002; Lustberg and Silbergeld

2002). Lustberg

and Silbergeld

(2002) analyzed

data for personsof all racesand concluded that risk of mortality from all causes,

circulatory

disease, and cancer
was elevated

for persons

with blood lead levels of 20-29 ,ug/dLcompared with those with levels < 10 pg/dL. Multivariate-adjusted results did not show an increased riskfor those with blood lead levels of 10-19 pg/dL. In an analysislimited to white participants, Jemal et al. (2002) found no dose-responserelationship between quartiles

of blood lead and risk of death from cancer, but they did find evidence of a threshold effect for women, with riskbecomingsignificantly elevated at a blood lead concentration

of approximately

24 pg/dL. The results

of our study showingincreased mortality at levels as low as 5-9 pg/dL areconsistentwith other research that suggests

health effectsassociated

with low levels of lead exposure.Recentcross-sectional analyses of the current, ongoing NHANES, with data from 1999-2002, suggest

an increased

risk of peripheral arterial disease, hypertension,

and renaldysfunctionin a population

with blood lead levels of approximately

2 pg/dLon average

(Muntner et al. 2005; Navas-Acien et al. 2004). Other analysesof population-based studies support these results. For example, in the Normative Aging Study,

blood leadlevels< 10 pg/dLwere associatedwith renal function and cognitive impairment (Kim et al. 1996; Payton et al. 1994, 1998; Weisskopf et al. 2004; Wright et al. 2003). Cross-sectional analyses of the NHANES III cohort have shown that blood lead levels are related

to increased

blood pressure (Nash et al. 2003) and decreased renal function(Muntner

et al. 2003). Exposure

misclassification

is a potentially important

limitation of our analysis. We classified exposure based on blood lead levels

2.0
1.8
1 .6 *E1.4\

co co 1.2
CD 1.2 i0 77777 0000tS0 0t0

~0.8
0.6
0.4
0.2
0.0I 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0

Bloodlead (gg/dL) Figure 1. Relative risk of all cause mortality

fordifferentblood

lead levels compared

with referent levelof 1.5pg/dL

(12.5th percentile).

The solid line shows the fitted

five-knot splinerelationship;

the dashedlines are the point-wise upper andlower 95% Cls. Table 2. Multivariate

adjusteda

relative risksfor all-cause, cancer, and cardiovascular disease mortality by bloodlead level and age category. Cause of death/ No.of Relative risk (95% Cl) by age category

(years) blood leadlevel deaths 40-74 75-84 > 85 All
All causes < 5pg/dL 1,402 1 1 1 1 5-9 pg/dL 828 1.30(1.03-1.65) 1.38 (1.04-1.83) 0.98(0.85-1.14) 1.24 (1.05-1.48) ? 10 pg/dL 255 1.73 (1.28-2.35)b 1.39(0.93-2.08)c 1.67(1.11-2.53) 1.59(1.28-1.98)b Cardiovascular

disease
< 5pg/dL 684 1 1 1 1 5-9 pg/dL 394 1.11(0.79-1.56) 1.41(0.87-2.28) 1.07(0.87-1.31) 1.20 (0.93-1.55) 2 10 pg/dL 111 1.47(0.93-2.33) 1.71 (0.94-3.09)c 1.45(0.85-2.48) 1.55(1.16-2.07)d Cancer
< 5 pg/dL 282 1 1 1 1 5-9 pg/dL 194 1.44(0.91-2.28) 1.46 (1.03-2.07) 1.44

(0.92-2.26) 1.44

(1.12-1.86) ? 10 pg/dL 67 2.27(1.38_3.74)d 0.80(0.38-1.69) 2.2 (1.13-4.29)d 1.69 (1.14-2.52)d Cl, confidence

interval. 8Adjusted for sex, race/ethnicity,

education, and smoking status. bp-Value for trend test < 0.001.

cp-Value for trend test < 0.05. dp-Value for trend test < 0.01.



### 1540 VOLUME 1141NUMBER

10 1 October

2006 * Environmental

Health Perspectives

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### Blood lead levels and mortality risk,NHANES

Ill

measured at only one point in time. Most (75-95%) lead in the body is found in bone (Saltzmanet al. 1990), where the half-life is 5-19 years (Rabinowitz 1991). Therefore,

measures of bone lead indicate cumulative, long-term

exposure and arethe bestmeasure

to study chronic effects. The half-life of lead in blood is approximately

1 month (Rabinowitz et al. 1976); thus blood levels are related to currentexposure.Lead is released from bone throughresorption,

such as occurs

with aging, and this contributesto levels found in blood (Hu et al. 1998; Smith et al. 1996). Olderpersons in the NHANES III cohort were more likelyto havehighercumulative lead exposure, and their blood lead levels may be disproportionately influenced by release of lead from bone stores

compared

with younger

persons. That our results

show an increased

riskof mortality at lower blood lead levels than the mortality studies of the NHANES II cohort may be related

to exposure

classification

being based on a single blood lead measurement. Blood lead levelsof NHANES III participants

werecloseto 80% lowerthan in the NHANES II cohort, and few adults had blood lead levels
> 20 pg/dL (CDC 1997; Pirkle et al. 1994). This reflects

reductions

in the current

exposure of the study participants

because of the elimination of lead from gasoline and other environmental sources. We speculate that the difference

in cumulative

lead exposure

among adults across the two surveys is relatively smaller than the difference

in current

exposure. For example, it is likely that within the same birthcohort,most persons who had blood lead levels > 20 ng/dL in 1976-1980 would have levels < 10 pg/dL in 1988-1994. The particularly dramatic decrease in blood levels that occurred during the NHANES II (Annest et al. 1983) makes the evaluation of a doseresponserelationshipof blood lead level and mortality even more problematic and may explain why the previous

analyses of NHANES II Uemal et al. 2002; Lustberg and Silbergeld 2002) did not find as stronga dose effectas in

our present analyses

of NHANES III, which had morestable

blood leadlevels. It is not possible to differentiate an acute effectof lead in blood from a chroniceffectin studiesthat only use blood lead levelsto indicate exposure

(Hu et al. 1998). With advances in measuring

bone lead through

X-rayfluorescence,several

studies haveevaluated

the association of health effects with both bone and blood lead measures.

Both cross-sectional

and longitudinal

analyses of the Normative

Aging Studysuggest

that cumulative

exposure, as well

as current

exposure,

to lead is associated

with declines in renal function (Kim et al. 1996; Payton et al. 1994) and cognition (Payton et al. 1998; Weisskopf et al. 2004; Wright et al. 2003). Results

fromthe Normative

Aging Study suggest

that cumulative

but not current 

### exposure

is associated

with an increased

risk of hypertension

(Tsaih et al.2004);

however, in a longitudinal

study of a cohort

who hadpreviousoccupational

exposure, Glenn et al. (2003) concluded that theeffect oflead on bloodpressure is consistent

withbothacute

and chronic modes ofaction. From the present

study we conclude

that mortality is associated

with leadexposure

as indicated by a single

blood lead measurement typical for the U.S. adult

population

during 1988-1994. Extrapolating

from thisto mortality risk related to cumulative

lead exposure or blood lead measurements fromdifferent calendar periods canonlybe speculative.

The blood lead andmortality

relationship

that we observed may be dueto lead

being a surrogate for someother

factor thatis associated

with
an increase

in mortality.

Forexample,

socioeconomic status maynot be sufficiently

controlled for by measures

of education

levelor family income. However, we adjusted

for well-know

confounders

without observing a substantial reduction in the blood lead relationship.

Also,the observed

relationships foreach category of mortality

were fairlyconsistent across age and groups. The major

strengths of our study, that the NHANES

cohort is representative

of the U.S. population

and that the sample

size is large enough to evaluate

small differences

in risk,
are notable. Ouranalysis

adds to the bodyof evidence demonstrating

adverse healthconsequences related to bloodleadlevels

that fall below currentlevels of concern. Further research is needed to assess cumulative

xposure and adverse health consequences,

including mortality, for persons who were not exposed to highlevels

of lead in the environment that were typical before lead was 

### removed from gasoline in thelate 1970s.

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