Background: Experimental studies have suggested that cadmium (Cd) exposure is a potential risk factor for early atherosclerosis and cardiovascular diseases as it can disrupt integrity of the endothelial cell layer. However, longitudinal data in humans relating Cd levels to sub-clinical atherosclerosis are lacking. Methods: 2589 participants from the CARDIA Study, aged 20-32 years in 1987 (baseline) with up to 18 years of follow-up were included in the analyses to examine prospectively the associations of toenail Cd concentrations with carotid intima-media thickness (CIMT) and coronary artery calcium score (CAC score). Toenail clippings were collected in 1987 and Cd was assessed by instrumental neutron-activation analysis. Common (c), bulb (b), and internal (i) CIMTs were measured in 2005 and CAC score in 2000 and 2005. CAC presence (score, >0 Agatston units) and CAC progression (incident CAC in 2005 or increase in CAC score by ≥10 Agatston units) were defined based on CAC score. General linear regression or logistic regression was used as appropriate. Results: Median Cd levels were 0.003, 0.006, 0.012 and 0.039 μ g/g from 1 st - 4 th quartile. We observed a positive linear relation of Cd levels with cCIMT, but not bCIMT and iCIMT ( Table 1 ). Null associations between Cd levels and CAC progression [Q 4 vs . Q 1 : OR=1.11 (95% CI: 0.73, 1.68); P trend =0.14] or presence of CAC [Q 4 vs . Q 1 : OR=1.05 (0.73, 1.53); P trend =0.56] were documented. Conclusions: In this young adult cohort, toenail Cd levels were positively associated with cCIMT, but not bCIMT, iCIMT and CAC score. Further studies are needed to determine whether there is an atherosclerotic mechanism linking Cd exposure to the risk of cardiovascular disease. Table 1 Multivariable-adjusted carotid intima-media thickness (mm) by toenail cadmium levels No. of participants Quartile of toenail cadmium levels P trend Q1 Q2 Q3 Q4 cCIMT 2587 0.781 (0.773-0.790) 0.784 (0.776-0.793) 0.789 (0.781-0.798) 0.791 (0.781-0.798) 0.03 bCIMT 2527 1.010 (0.990-0.1.031) 1.002 (0.982-1.022) 0.981 (0.962-1.001) 1.001 (0.980-1.022) 0.17 iCIMT 2436 0.787 (0.772-0.802) 0.790 (0.776-0.804) 0.784 (0.770-0.798) 0.778 (0.763-0.793) 0.86 Data are geometric means (95%CIs) adjusted for age, gender, race, study center, body mass index, physical activity, education, smoking status, alcohol consumption, systolic blood pressure, LDL/HDL, HOMA, body mass index, long-chain omega-3 polyunsaturated fatty acids intake with toenail zinc, chromium, lead and mass weight. cCIMT : common carotid intima-media thickness; bCIMT : bulb carotid intima-media thickness; iCIMT : internal carotid intima-media thickness.
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