Biological Age Mediates the Effects of Perceived Neighborhood Problems on Heart Failure Risk Among Black Persons

Objective We assessed whether biological age, measured by the epigenetic clock GrimAge, mediates the association of objective and subjective neighborhood disadvantage with incident HF among Black persons. Methods Participants were 1448 self-reported Black adults (mean age (standard deviation, SD) = 64.3 (5.5)) dually enrolled in two community-based cohorts in Jackson, Mississippi, the ARIC and JHS cohorts, who were free of HF as of January 1, 2000. Incident HF events leading to hospitalization through December 31, 2017, were classified using ICD-9 discharge codes of HF. Multilevel age- and sex-adjusted Cox causal mediation models were used to examine whether biological age (at the person and neighborhood level) mediated the effects of objective (the National Area Deprivation Index, ADI) and subjective (perceived neighborhood problems) neighborhood disadvantage on incident HF. Results A total of 334 incident hospitalized HF events occurred over a median follow-up of 18.0 years. The total effect of the ADI and perceived neighborhood problems (SD units) on HF was hazard ration (HR) = 1.26 and 95% confidence interval (CI) 0.98–1.56 and HR = 1.26 and 95% CI 1.10–1.41, respectively. GrimAge mediated a majority of the effect of perceived neighborhood problems on HF (person-level indirect effect HR = 1.07; 95% CI 1.02–1.12 and neighborhood-level indirect effect HR = 1.18; 95% CI 1.03–1.34), with the combined indirect effect explaining 94.8% of the relationship. The combined indirect effect of ADI on incident HF was comparable but not statistically significant. Conclusions Subjective neighborhood disadvantage may confer an increased risk of HF among Black populations.