associated with DBP in both males (β = 2.93 mm Hg; 95% CI: 0.93, 4.98, for every 1 natural log unit of BLL) and females (β = 1.64 mm Hg; 95% CI: 0.27, 3.01) (Schwartz 1991). Those results suggest that a dose-response relationship between BLL and blood pressure is most likely log-linear.
Clinical Cardiovascular Outcomes
Navas-Acien et al. (2007) conducted a qualitative systematic review of lead exposure and cardiovascular end points except blood pressure and hypertension. They identified 12 studies of clinical cardiovascular end points in general populations and 18 studies of cardiovascular mortality in occupational cohorts. They concluded that the evidence was suggestive but not sufficient to infer causal relationships between lead exposure and clinical cardiovascular outcomes because of the small number of prospective studies, the lack of standardized assessment and information on outcomes, and methodologic limitations, such as exposure and outcome misclassification.
The committee identified one study of an important and specific clinical outcome—incident ischemic heart disease—and four studies of cardiovascular mortality. Jain et al. (2007) examined the association between bone lead and incidence of ischemic heart disease (myocardial infarction or angina pectoris) in a prospective cohort of veterans in the Boston, Massachusetts, area (Normative Aging Study: 83 cases and 754 noncases) with 10 years of followup. The mean (SD) concentrations of baseline BLL, patella lead, and tibia lead were 7.0 (3.8) μg/dL, 36.8 (20.8) μg/g, and 24.2 (15.9) μg/g in cases and 6.2 (4.3) μg/dL, 30.6 (19.7) μg/g, and 21.4 (13.6) μg/g in noncases, respectively. SD increases in BLL and patella lead were significantly associated with a 27% (95% CI of hazard ratio [HR]: 1.01, 1.59) and a 29% (95% CI of HR 1.02, 1.62) increased risk of ischemic heart disease. Compared with subjects who had BLLs under 5 μg/dL, those who had BLLs of 5 μg/dL or higher had an HR of 1.73 (95% CI: 1.05, 2.87). Weisskopf et al. (2009) conducted a survival analysis of mortality in the same cohort (an average of 8.9 years of followup) and found that men in the highest tertile of patella lead had HRs of 2.52 (95% CI: 1.17, 5.41) for all causes, 5.63 (95% CI: 1.73, 18.3) for cardiovascular disease, and 8.37 (95% CI: 1.29, 54.4) for ischemic heart disease. Baseline BLLs were not associated with cardiovascular mortality.
The committee identified other important studies. A study that used data from NHANES II reported a rate ratio of 1.39 (95% CI: 1.01, 1.91) for circulatory mortality associated with BLLs of 20-29 μg/dL compared with BLLs under 10 μg/dL (Lustberg and Silbergeld 2002). Lin et al. (2011) followed 927 dialysis patients in Taiwan for 18 months and found that after adjustment for confounders the upper two tertiles of BLLs (8.51-12.64 μg/dL and over 12.64 μg/dL) were associated with HRs of 3.70 (95% CI: 2.06, 6.48) and 9.71 (95% CI: 2.11,