BONE LEAD LEVELS IN RELATION TO BASELINE PULSE PRESSURE: THE NORMATIVE AGING STUDY

Abstract

ISEE-368 Background: The lead-exposed rat demonstrates increased vascular reactive oxygen species (ROS), and blood lead level has been positively correlated with increased plasma markers of oxidative stress in humans. ROS contribute to vascular pathophysiology, one manifestation of which is an increase in the pulse pressure [the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP)]. We hypothesized that lead exposure might predict pulse pressure in humans. Methods: In a substudy of the Normative Aging Study, a longitudinal cohort of male veterans, we measured participants' bone lead level using K-shell x-ray fluorescence and blood pressure using standard mercury sphygmomanometry. Subjects were included if they had satisfactory bone lead and blood pressure determinations and were excluded if they were taking antihypertensives. A total of 598 men, aged 48-93, met these criteria. Using simple and multiple linear regression, we computed the difference in pulse pressure associated with progressively higher levels of bone lead. We could not assume a linear association between bone lead and pulse pressure, therefore we examined bone lead in quintiles. Results: The mean levels of tibia lead among the first through the fifth quintiles were 7.4, 14.1, 18.9, 24.9, and 40.8 micrograms per gram, respectively. Pulse pressure ranged from 21 to 95 mm Hg with a mean of 53 mm Hg. In unadjusted analyses, tibia lead levels were positively associated with SBP and negatively associated with DBP. Higher tibia lead level was associated with progressively higher pulse pressure after adjusting for age, age squared, family history of hypertension, fasting plasma glucose, and alcohol intake. Compared with the pulse pressure of men in the lowest quintile of tibia lead, the mean differences in pulse pressure in the second through the fifth quintiles, respectively, were -2.7, -0.08, 2.56, 3.25, p value for trend 0.006. Conclusion: We found that bone lead level independently predicted pulse pressure. This is consistent with lead exposure contributing to ROS mediated vascular pathophysiology. This finding may shed light on previous work in which the positive association of lead with SBP and the negative association of lead with DBP were interpreted as inconsistent.