Cardiovascular
Urinary metal mixtures and incident cardiovascular disease and all-cause mortality in an ethnically diverse population of adults: evidence from the Multi-Ethnic Study of Atherosclerosis (MESA) Irene Martinez-Morata* Irene Martinez-Morata Kathrin Schilling Ronald A. Glabonjat Arce Domingo-Relloso Melanie Mayer Katlyn McGraw Tiffany Sanchez Joel Kaufman Dhananjay Vaidya Miranda R. Jones Michael P. Bancks Daichi Shimbo R.Graham Barr Wendy Post Linda Valeri Steven Shea Ana Navas-Acien
Background: Environmental metals are increasingly recognized as risk factors for cardiovascular disease (CVD) and mortality, yet prospective studies assessing the impact of metal mixtures, which are more likely to mimic real-life exposures, are limited. We assessed prospective associations of two multi-metal panels measured in urine with incident CVD and mortality in a population of adults from the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: A total of 6,599 participants (mean age 62.1 years, 53% female, 39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese) with urinary metals available at baseline (2000-2001) were followed through December 2019. A multi-element panel of n=15 metals were measured. Six metals (cadmium, tungsten, uranium, cobalt, copper, and zinc) were selected as priority following previous evidence. Progressively adjusted Cox proportional hazards models with an Elastic-Net penalty were used to estimate the hazard ratio (HR) and 10-year survival probability of incident CVD (fatal and non-fatal) and all-cause mortality per one interquartile range (IQR) difference in baseline urinary metals. The levels of i) the six priority metals, and ii) all metals available (n=15) were included in the Elastic-Net constraint as the mixtures. Sociodemographic, behavioral, and clinical covariates were forced into the models as potential confounders.
Results: Over 17.7 years median follow-up, 1,162 participants developed CVD and 1,844 died. All the priority metals were selected by the Elastic-Net. In the models adjusted by sociodemographic, behavioral, and clinical factors, the HR (95%CI) and 10 year-survival probability difference per one IQR increase in the priority metals mixture were, respectively 1.29 (1.11, 1.56), -1.1% (-2.0, -0.5) for incident CVD; and 1.66 (1.47, 1.91), -2.0% (-2.6, -1.5) for all-cause mortality. For the n=15 metals models, the covariate-adjusted HR and 10 year-survival probability difference were 1.27 (1.07, 1.59), -1.0% (-1.9, -0.3) for incident CVD; and 1.39 (1.19, 1.62), -1.3% (-1.9, -0.7) for mortality, respectively.
Conclusion: This large epidemiological study in US adults indicate that higher urinary metal levels, when analyzed as a mixture, are associated with increased risk of incident CVD and all-cause mortality.