Abstract Body: Background: Environmental metals are recognized risk factors for cardiovascular disease, yet the role of urinary metals and metal mixtures on incident heart failure (HF) remains understudied.
Objectives: To evaluate the prospective association of urinary metals on incident HF risk across three geographically and ethnically/racially diverse cohorts: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS) in the United States, and the Hortega cohort in Spain.
Methods: A total of 6,644, 2,917, and 1,334 adults 35-80 years old were included across MESA (39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese-descent), SHS (100% American Indian), and Hortega (100% white), and followed up to 19 years. Urinary levels of inorganic arsenic, cadmium, molybdenum, selenium, and zinc were measured in all cohorts at baseline. The multi-adjusted (sociodemographic + clinical covariates) hazard ratios (HR) of HF per one interquartile range (IQR) difference in urinary metals were estimated for each metal using Cox proportional hazard models and a fixed-effects meta-analysis was run for each metal across cohorts. Flexible dose-response assessment was conducted using quadratic splines. We further estimated the HRs and 10-year-survival probability difference per IQR change in the mixture of five metals using Cox proportional hazard models with an Elastic Net penalty.
Results: A total of 425 (MESA), 477 (SHS), and 103 (Hortega) participants developed HF over the study follow-up. Significant associations were identified for arsenic (Pooled HR (95%CI): 1.06 (1.00, 1.12), cadmium (HR: 1.15 (1.07, 1.24)), molybdenum (HR:1.14 (1.03, 1.26)), and zinc (HR: 1.23 (1.02, 1.49)) in the meta-analyses (Figure 1). A largely linear dose-response was identified for arsenic and cadmium (Figure 2). In fully adjusted models, the HRs (95% CI) and 10-year survival probability differences (95% CI) of incident HF per one IQR increase in the metal mixture were, respectively, 1.38 (1.00, 1.86) and -0.40 (-0.78, 0.00) in MESA, 1.55 (1.28. 1.97) and -1.24 (-2.20, -0.59) in SHS, and 1.08 (0.85, 1.63), and -0.03 (-0.21, 0.06) in Hortega.
Conclusion: This multi-cohort study identified consistent associations between higher urinary metals and increased risk of heart failure across diverse populations, supporting the role of prevention strategies to reduce contaminant metal exposure to lower HF risk.