Arsenic Exposure and Epigenetic Aging: The Association with Cardiovascular Disease and All-Cause Mortality in the Strong Heart Study.

BACKGROUND: Inorganic arsenic (As) may increase the risk of cardiovascular disease (CVD) and all-cause mortality through accelerated aging, which can be estimated using epigenetic-based measures. OBJECTIVES: We evaluated three DNA methylation-based aging measures (PhenoAge, GrimAge, DunedinPACE) (epigenetic aging measures) 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 Indian adults. METHODS: Blood DNA methylation and urinary As levels were measured in 2,323 SHS participants (41.5% men, mean age of 55 years old). PhenoAge and GrimAge values were calculated using a residual-based method. We tested the association of urinary As with epigenetic aging measures using linear regression, the association of epigenetic aging measures with the three health outcomes using additive hazards models, and the mediation of As-related CVD incidence, CVD mortality, and all-cause mortality by epigenetic aging measures using the product of coefficients method. RESULTS: SHS participants with higher vs. lower urinary As levels had similar PhenoAge age, older GrimAge age, and faster DunedinPACE. An interquartile range increase in urinary As was associated with higher of PhenoAge age acceleration [mean difference (95% confidence interval)=0.48 (0.17, 0.80) years], GrimAge age acceleration [0.80 (0.60, 1.00) years], and DunedinPACE [0.011 (0.005, 0.018)], after adjusting for age, sex, center location, genetic components, smoking status, and body mass index. Of the 347 incident CVD events per 100,000 person-years associated with a doubling in As exposure, 21.3% (9.1, 57.1) and 22.6% (9.5, 56.9), were attributable to differences in GrimAge and DunedinPACE, respectively. DISCUSSION: 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. https://doi.org/10.1289/EHP11981.

Pharmacological management of cerebral ischemia in the elderly.

Introduction: For elderly adults in the United States, stroke is the fifth leading cause of death of which ischemic strokes comprise a vast majority. Optimal pharmacological management of elderly ischemic stroke patients involves both reperfusion and supportive care. Recent research into pharmacological management has focused on vascular, immunomodulatory, cytoprotective, and alternative agents, some of which have shown limited success in clinical trials. However, no treatments have been established as a reliable mode for management of cerebral ischemia for elderly adults beyond acute thrombolysis.Areas covered: The authors conducted a literature search for ischemic stroke management in the elderly and a search for human drug studies for managing ischemic stroke on clinicaltrials.gov. Here, they describe recent progress in the pharmacological management of cerebral ischemia in the elderly.Expert opinion: Many drug classes (antihypertensive, cytoprotective and immunomodulatory, and alternative agents) have been explored with limited success in managing ischemic stroke, though some have shown preventative benefits. We generally observed a broad gap in evidence on elderly patients from studies across all drug classes, necessitating further studies to gain an understanding of effective management of ischemic stroke in this large demographic of patients.