Arsenic Exposure and Accelerated Aging: The Association with Cardiovascular Disease and All-Cause Mortality in the Strong Heart Study
Year: 2023
Type: conference-abstract
Abstract: BACKGROUND AND AIM: Inorganic arsenic (As) may increase the risk of cardiovascular disease (CVD) and all-cause mortality through accelerated aging, which can be measured by epigenetic-based measures. We evaluated three DNA methylation-based aging measures (PhenoAge, GrimAge, DunedinPACE) as potential mediators of the previously reported association of As exposure with CVD incidence, CVD mortality, and all-cause mortality in the Strong Heart Study (SHS), an epidemiological cohort of American Indians. METHOD: Blood DNA methylation and urinary As levels were measured in 2,323 SHS participants (41.5% men, mean age 55 years). PhenoAge and GrimAge values were calculated using a residual-based method. We tested the association of As with epigenetic aging measures using linear regression, and conducted a mediation analysis of As-related CVD incidence, CVD mortality, and all-cause mortality by epigenetic aging measures using additive hazards models. RESULTS: SHS participants with higher vs. lower urinary-As levels had similar PhenoAge age, older GrimAge age, and faster DunedinPACE. Comparing the 75th vs. 25th percentiles of GrimAge and DunedinPACE, participants with older GrimAge and faster DunedinPACE were at increased risk for incident CVD [GrimAge HR=1.29 95%CI (1.16, 1.43); DunedinPACE HR=1.27 (1.16, 1.39)], CVD mortality [GrimAge 1.75 (1.46, 2.11); DunedinPACE HR=1.50 (1.28, 1.77)], and all-cause mortality [GrimAge HR=1.78 (1.61, 1.97); DunedinPACE HR=1.46 (1.34, 1.60)]. In mediation analyses, GrimAge and DunedinPACE mediated 10.3-20.7% of associations between As and the three health outcomes. CONCLUSIONS: Arsenic exposure was associated with older GrimAge and faster DunedinPACE measures of biological age. Furthermore, accelerated biological aging measured from DNA methylation accounted for a relevant fraction of As-associated risk for CVD, CVD mortality, and all-cause mortality in the SHS, supporting the role of As in accelerated aging. Research of the biological underpinnings can contribute to a better understanding of the role of aging in arsenic-related disease.
Source: ISEE Conference Abstracts
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W4390965378