in adults who have mean bone lead concentrations over 20 μg/g. Overall, the 2012 report suggested that the available data are sufficient to conclude that there is a causal association between lead exposure and several specific cardiovascular health effects. The report also pointed out that uncertainty exists as to the lead exposure level, timing, frequency, and duration that contribute to the observed associations because the adult populations examined in the epidemiologic research probably had high past lead exposures.

National Toxicology Program 2012 Monograph on Health Effects of Low-Level Lead

The NTP concluded that there is sufficient evidence that BLLs under 10 μg/dL are associated with increased blood pressure and hypertension in adults but that the evidence is limited with respect to associations with cardiovascular-related mortality and other cardiovascular end points, such as ECG conduction abnormalities, heart-rate variability, and clinical cardiovascular diseases. The NTP also indicated that bone lead has been more consistently associated with chronic cardiovascular outcomes, such as hypertension and cardiovascular mortality, than BLL; this suggests that long-term cumulative exposure as measured by bone lead is more critical than concurrent lead exposure reflected by BLLs with regard to chronic cardiovascular outcomes.

Other Studies Considered

Blood Pressure and Hypertension

Two meta-analyses integrated most published studies of the associations of blood pressure and hypertension with BLL and bone lead. Nawrot et al. (2002) examined 31 US and European studies published during 1980-2001 and used the following inclusion criteria: 50 or more subjects, ages 10 years and over, both blood pressure and BLL measurements presented with sufficient detail to estimate the magnitude of the association, and preference given to studies that adjusted for age, body-mass index, and additional factors of proven importance. The meta-analysis, whenever possible, analyzed sex-specific and race-specific associations separately. The combined analysis included 58,518 subjects for systolic blood pressure (SBP) and 58,491 subjects for diastolic blood pressure (DBP). The mean BLL ranged from 2.28 to 63.82 μg/dL (median 12.64 μg/dL; interquartile range 7.46-23.93 μg/dL). The combined overall association sizes for SBP and DBP for each two-fold increase in BLL were 1.0 mm Hg (95% CI: 0.5, 1.4) and 0.6 mm Hg (95% CI: 0.4, 0.8), respectively. Sex differences in the associations of BLL with SBP and DBP were not statistically significant.

Navas-Acien et al. (2008) performed a meta-analysis of the associations of bone lead concentration with blood-pressure outcomes based on three prospective



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