TPS 636: Metals and health 2, Johan Friso Foyer, Floor 1, August 28, 2019, 3:00 PM - 4:30 PM Background/Aim: While the evidence supporting a causal association of metals with clinical cardiovascular disease is substantial, fewer studies have evaluated subclinical atherosclerosis. We tested the association of non-essential metals with subclinical atherosclerosis by using genetic polymorphisms in candidate genes as a proxy of unconfounded metal exposure. Methods: Urine Antimonium (Sb), Barium (Ba), Cadmium (Cd), Chromium (Cr), Titanium (Ti), Tungsten (W), Uranium (U) and Vanadium (V), and urine Arsenic (As) speciation, were measured by ICPMS and HPLC-ICPMS, respectively, in 1815 workers from a car assembly factory in Figueruelas (Spain) participating in the Aragon Workers’ Health Study. Atherosclerosis presence (yes/no) was measured in carotid and femoral arteries with ultrasounds, and in coronary arteries with NMR. For statistically significant metals in traditional logistic models, we evaluated the association of genetically controlled biomarker levels with atherosclerosis presence using 2-stage least squares Mendelian Randomization methods. Results: The geometric mean of Sb, sum of inorganic As (∑iAs), Ba, Cd, Cr, Ti, W, U and V was 0.22, 8.1, 1.88, 0.43, 1.06, 213.05, 0.23, 0.03, and 0.5 μg/g, respectively. In multi-adjusted models (including arsenobetaine adjustment for ∑iAs), the odds ratio (95% CI) for atherosclerosis presence in any of the evaluated vascular territories were, 1.21 (1.00-1.46) for ∑iAs, 1.60 (1.17-2.19) for Cd and 1.26 (1.05-1.52) for Ti. These associations were driven by ∑iAs and Cd in carotid, Cd and Ti in femoral and Ti in coronary territories. For ∑iAs the associations of genetically-elevated concentrations (3 ∑iAs-associated SNPs) were statistically significant and directionally consistent compared to the observational associations. For Cd the corresponding associations (2 Cd-associated SNPs) were only consistent in femoral atherosclerosis models. Conclusions: Replication of findings is needed. Our results, however, support a role of As and Cd as cardiovascular risk factors. Reinforced exposure reduction interventions may decrease cardiovascular disease.