Abstract
BACKGROUND: Environmental metals are recognized cardiovascular disease risk factors, yet the role of metal exposure in heart failure (HF) risk remains understudied.
OBJECTIVES: This study aims to evaluate the prospective association of urinary metals with incident HF across 3 geographically and ethnically/racially diverse cohorts: MESA (Multi-Ethnic Study of Atherosclerosis) and SHS (Strong Heart Study) in the United States, and the Hortega Study in Spain.
METHODS: Adults 18-85 years of age in MESA (n = 6,601), SHS (n = 2,917), and Hortega (n = 1,300) were followed up to 20 years. Urinary levels of a multi-metal panel were measured at baseline and corrected for urine dilution. Cox proportional hazards and Cox elastic-net models were used to estimate the multi-adjusted (sociodemographic/clinical/lifestyle covariates) HR of incident HF by individual metals and the mixture of 5 metals available in all cohorts, respectively. The pooled HR (95% CI) of HF by 1-unit increase in log2-transformed levels of individual metals (ie, doubling of the dose) across cohorts was estimated using a fixed effects meta-analysis. Analyses by left ventricular ejection fraction were conducted in a subset.
RESULTS: A total of 1,001 participants developed HF. In adjusted models, significant associations (pooled HRs [95% CI] per doubling of urinary metal) were identified for cadmium (HR: 1.15 [95% CI: 1.07-1.24]) molybdenum (HR: 1.13 [95% CI: 1.05-1.22]), and zinc (HR: 1.22 [95% CI: 1.14-1.32]). The HRs (95% CIs) for the association of 1 IQR increase in the multi-metal mixture levels and incident HF were 1.38 (95% CI: 1.00-1.86) in MESA, HR: 1.55 (95% CI: 1.28-1.97) in SHS, and HR: 1.08 (95% CI: 0.85-1.63) in Hortega in fully adjusted models. Stratified models by left ventricular ejection fraction were consistent with the pooled results.
CONCLUSIONS: Urinary metals are risk factors of HF across 3 diverse populations, supporting the role of reducing metal exposures to lower HF risk.