Blood Lead and Other Metal Biomarkers as Risk Factors for Cardiovascular Disease Mortality

• Published in: Medicine (Baltimore) Vol. 95; no. 1; p. e2223
• Main Authors: Aoki, Yutaka, Brody, Debra J., Flegal, Katherine M., Fakhouri, Tala H.I., Axelrad, Daniel A., Parker, Jennifer D.
• Format: Journal Article
• Language: English
• Published: United States The Authors. Published by Wolters Kluwer Health, Inc. Health, Inc. All rights reserved 01.01.2016; Wolters Kluwer Health
• Subjects: Adult; Aged; Alcohol Drinking - epidemiology; Biomarkers; C-Reactive Protein - analysis; Cadmium - blood; Cardiovascular Diseases - ethnology; Cardiovascular Diseases - mortality; Cause of Death; Female; Hematocrit; Hemoglobins; Humans; Iron - blood; Lead - blood; Male; Middle Aged; Nutrition Surveys; Observational Study; Proportional Hazards Models; Residence Characteristics; Risk Factors; Sex Factors; Smoking - epidemiology; United States; United States
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000002223

Analyses of the Third National Health and Nutrition Examination Survey (NHANES III) in 1988 to 1994 found an association of increasing blood lead levels < 10 μg/dL with a higher risk of cardiovascular disease (CVD) mortality. The potential need to correct blood lead for hematocrit/hemoglobin and adjust for biomarkers for other metals, for example, cadmium and iron, had not been addressed in the previous NHANES III-based studies on blood lead-CVD mortality association. We analyzed 1999 to 2010 NHANES data for 18,602 participants who had a blood lead measurement, were ≥ 40 years of age at the baseline examination and were followed for mortality through 2011. We calculated the relative risk for CVD mortality as a function of hemoglobin- or hematocrit-corrected log-transformed blood lead through Cox proportional hazard regression analysis with adjustment for serum iron, blood cadmium, serum C-reactive protein, serum calcium, smoking, alcohol intake, race/Hispanic origin, and sex. The adjusted relative risk for CVD mortality was 1.44 (95% confidence interval = 1.05, 1.98) per 10-fold increase in hematocrit-corrected blood lead with little evidence of nonlinearity. Similar results were obtained with hemoglobin-corrected blood lead. Not correcting blood lead for hematocrit/hemoglobin resulted in underestimation of the lead-CVD mortality association while not adjusting for iron status and blood cadmium resulted in overestimation of the lead-CVD mortality association. In a nationally representative sample of U.S. adults, log-transformed blood lead was linearly associated with increased CVD mortality. Correcting blood lead for hematocrit/hemoglobin and adjustments for some biomarkers affected the association.