Lead Concentrations in Relation to Multiple Biomarkers of Cardiovascular Disease: The Normative Aging Study

Background: Lead exposure has been associated with cardiovascular disease (CVD) in animal and human studies. However, the mechanisms of action have not been fully elucidated. We therefore examined the relationship between lead and multiple biomarkers of CVD. Methods: Participants were older men from the Normative Aging Study without preexisting coronary heart disease, diabetes, or active infection at baseline (n = 426). Serum biomarkers included lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides] and inflammatory markers [C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor receptor-2 (TNF-R2)]. We measured lead in blood and in bone by K-shell X-ray fluorescence. In this sample, 194 men (44.3%) had two or more repeated measures, resulting in 636 observations for analysis. We conducted analyses using mixed effects models with random subject intercepts. Results: Lead levels were associated with several CVD biomarkers, including levels of TNF-R2 and lipid markers. Specifically, in multivariable models, a 50% increase in blood lead level was associated with 26% increased odds of high TNF-R2 levels (> 5.52 ng/mL; odds ratio = 1.26; 95% confidence interval: 1.09, 1.45). There were positive associations of blood lead level with total cholesterol and HDL levels, and these associations were more evident when modeled as continuous outcomes than when categorized using clinically relevant cut points. In addition, longitudinal analyses indicated a significant increase in TNF-R2 levels over time to be associated with high blood lead level at the preceding visit. Conclusions: Blood lead level may be related with CVD in healthy older men through its association with TNF-R2 levels. In addition, the magnitude of the association of blood lead level with TNF-R2 level increased with age in the study population.