title: Blood Lead and Other Metal Biomarkers as Risk Factors for Cardiovascular Disease Mortality.
abstract: 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.
authors.affiliation: From the Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Hyattsville, MD (YA, DJB, KMF, THIF, JDP); and Office of Policy, Environmental Protection Agency, Washington, DC, USA (DAA).
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoki
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Brody
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Flegal
authors.forename: Tala H I
authors.initials: THI
authors.lastname: Fakhouri
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Axelrad
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002104:Cadmium / Q000097:blood; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000401:mortality*; D002423:Cause of Death; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins; D006801:Humans; D007501:Iron / Q000097:blood; D007854:Lead / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D016016:Proportional Hazards Models; D012111:Residence Characteristics; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D014481:United States
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D002104:Cadmium; D007854:Lead; D002097:C-Reactive Protein; D007501:Iron