The association of urine metals and metal mixtures with cardiovascular incidence in an adult population from Spain: the Hortega Follow-Up Study

Abstract

Background: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain.

Methods: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting.

Results: In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities.

Conclusions: Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

Keywords: BKMR; Urine metals; cardiovascular incidence; cohort study; population-based.

Figure 1.

Overall association of the metal mixture with CVD incidence (difference in the probit of incident CVD hazard and 95% credibility intervals) when all predictors are at a particular percentile compared with the value when all of them are at their 50th percentile. BKMR-P models adjusted for sex, education (=high school), smoking status (never, former and current smoker), cumulative smoking dose (0, 0-12, >12 pack-years), urine cotinine (<34, 34–500 and >=500 ng/mL), age, estimated glomerular filtration rate (mL/min per 1.73m²), residence (urban or rural), HDL cholesterol level (mg/dl), total cholesterol level (mg/dl), dyslipidaemia treatment (yes/no), hypertension treatment (yes/no), diabetes mellitus of type 2 (yes/no) and systolic pressure (mmHg).