Registration Dossier

Administrative data

Endpoint:
epidemiological data
Type of information:
other: Epidemiological - Mortality
Adequacy of study:
supporting study
Study period:
1990-2003

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2009

Materials and methods

Study type:
cohort study (prospective)
Endpoint addressed:
not applicable
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Prospective cohort study

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
HYPOTHESIS TESTED: Women with blood lead concentrations above a threshold will experience higher total and cause specific mortality.

METHOD OF DATA COLLECTION
- Type: Questionnaire; interview; clinical examination; blood sample; mortality
- Details: Each participant completed a baseline questionnaire that ascertained her education and health behaviors including smoking, alcohol use, and exercise. Participants were also asked about diagnosed diabetes and hypertension and the use of estrogen. At baseline, each participant had her blood pressure, height and weight measured and body mass index (BMI) calculated. Whole blood was drawn for blood lead measurements. Participants were contacted every four months after baseline visits (1991-1992) over 12 years of follow-up. Deaths were confirmed by death certificates.

STUDY PERIOD: 1990-2003

SETTING: University of Pittsburgh and University of Maryland clinics

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 9704
- Selection criteria: Participants were women aged 65 years and older and ambulatory, and were selected from the Study of Osteoporotic Fractures (SOF), a longitudinal cohort study that enrolled 9704 white women from 1986 to 1988 using population-based listings in Baltimore, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley near Pittsburgh, PA.
- Total number of subjects participating in study: 533
- Sex/age/race: White women aged 65-87 years
- Smoker/nonsmoker: 12% of participants were current smokers
- Total number of subjects at end of study: 533

COMPARISON POPULATION
- Type: Internal
- Details: Participants were categorized into two groups based on blood lead level

HEALTH EFFECTS STUDIED
- Disease(s): Mortality
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: Environmental lead

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (blood)

EXPOSURE LEVELS: Mean blood lead concentration was 5.3 ± 2.3 μg/dL (range 1–21)

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: Lead concentrations were dichotomized above and below 8 μg/dL, thus the two groups were: < 8 μg/dL (referent, n = 454), and ≥ 8 μg/dL (n = 79).
Statistical methods:
The authors compared baseline characteristics by lead and mortality status, using chi-square tests for categorical variables and t-tests for continuous variables. Two-tailed p-values were used for all tests, at 5% statistical significance. Separate models were analyzed for all cause and cause specific mortality. Cardiovascular disease (CVD) mortality was categorized into two subgroups: deaths due to stroke, and coronary heart disease. Cox proportional hazards regression analysis were used to estimate the Hazard Ratio (HR) and 95% confidence intervals (CI) to determine association between blood lead concentration and mortality. The following variables were controlled for in all models: age increase per 5 years, clinic, BMI, education, smoking, alcohol intake, estrogen use, hypertension, total hip BMD, walking for exercise, and diabetes.

Results and discussion

Results:
A total of 123 (23%) women died over a mean follow-up of 12.0 (± 3) years. Women who died had 7% higher mean (± SD) blood lead [5.56 (± 3) μg/dL] than survivors: 5.17(± 2.0) μg/dL (p = 0.09). Women with baseline blood lead concentrations ≥ 8 μg/dL, had 59% increased risk of multivariate adjusted all-cause mortality (Hazard Ratio [HR] = 1.59; 95% confidence interval [CI], 1.02–2.49; p = 0.041), especially coronary heart disease (CHD) mortality (HR = 3.08; 95% CI, 1.23–7.70; p = 0.016), compared to women with blood lead concentrations < 8 μg/dL. There was no association of blood lead with stroke, cancer, or non-cardiovascular deaths.
Confounding factors:
Women with blood lead concentration ≥ 8 μg/dL had higher alcohol intake, were more likely to smoke, and had 8% lower total hip bone mineral density (BMD). As compared to survivors, women who died were older, more likely to smoke and to have hypertension. A lower proportion of women who died reported walking for exercise. Age, clinic, smoking, hypertension, and total hip BMD were significantly associated with mortality in women with blood lead concentration ≥ 8 μg/dL.
Strengths and weaknesses:
The authors noted that the strengths of their study include more than 95% complete follow-up for 12 years and controlling for a number of covariates and cardiovascular risk factors. The noted weaknesses include: participation limited to older Caucasian women, no determination of co-contaminants such as cadmium, no measures of factors that might influence the association between lead and mortality, and the possibility of some misclassification of the cause of death.

Applicant's summary and conclusion

Conclusions:
The authors concluded: "Women with blood lead concentrations of ≥ 8 μg/dL (0.384 μmol/L), experienced increased mortality, in particular from CHD as compared to those with lower blood lead concentrations."
Executive summary:

This prospective cohort study of 533 women aged 65 -87 aimed to determine the association between blood lead and all-cause and cause-specific mortality in elderly women. After collection of baseline data from 1990-1991, a total of 123 (23%) women died over a mean follow-up period of 12.0 (± 3) years. Women who died had 7% higher mean blood lead [5.56 (± 3) μg/dL] than survivors: 5.17(± 2.0) μg/dL (p = 0.09). Women with baseline blood lead concentrations ≥ 8 μg/dL, had 59% increased risk of multivariate adjusted all-cause mortality (Hazard Ratio [HR] = 1.59; 95% confidence interval [CI], 1.02–2.49; p = 0.041) especially coronary heart disease (CHD) mortality (HR = 3.08; 95% CI, 1.23–7.70; p = 0.016), compared to women with blood lead concentrations <8 μg/dL. There was no association of blood lead with stroke, cancer, or non-cardiovascular deaths. The authors concluded: "Women with blood lead concentrations of ≥ 8 μg/dL (0.384 μmol/L), experienced increased mortality, in particular from CHD as compared to those with lower blood lead concentrations."