Increasing mortality from suicide, drug overdose, and alcohol-related liver disease (collectively referred to as deaths of despair) is a critical public health crisis. Income inequality and social mobility have been separately associated with all-cause mortality; however, no studies have examined their interaction with these preventable deaths. To assess the interaction between income inequality and social mobility with deaths of despair among working-age Hispanic, non-Hispanic Black, and non-Hispanic White populations. This cross-sectional study analyzed data from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) database on county-level deaths of despair from 2000 to 2019 across racial and ethnic groups. Statistical analysis was performed from January 8 to May 20, 2023. The primary exposure of interest was county-level income inequality, measured by the Gini coefficient. Another exposure was race- and ethnicity-specific absolute social mobility. Tertiles for the Gini coefficient and social mobility were created to evaluate the dose-response association. The main outcomes were adjusted risk ratios (RRs) of deaths from suicide, drug overdose, and alcoholic liver disease. The interaction between income inequality and social mobility was formally tested on both the additive and multiplicative scales. The sample included 788 counties for Hispanic populations, 1050 counties for non-Hispanic Black populations, and 2942 counties for non-Hispanic White populations. Over the study period, 152 350, 149 589, and 1 250 156 deaths of despair were recorded for working-age Hispanic, non-Hispanic Black, and non-Hispanic White populations, respectively. Compared with the reference group (counties with low income inequality and high social mobility), counties with greater income inequality (high inequality: RR, 1.26 [95% CI, 1.24-1.29] for Hispanic populations; RR, 1.18 [95% CI, 1.15-1.20] for non-Hispanic Black populations; and RR, 1.22 [95% CI, 1.21-1.23] for non-Hispanic White populations) or less social mobility (low mobility: RR, 1.79 [95% CI, 1.76-1.82] for Hispanic populations; RR, 1.64 [95% CI, 1.61-1.67] for non-Hispanic Black populations; and RR, 1.38 [95% CI, 1.38-1.39] for non-Hispanic White populations) had higher RRs for deaths of despair. In counties with high income inequality and low social mobility, positive interactions were observed on the additive scale for Hispanic populations (relative excess risk due to interaction [RERI], 0.27 [95% CI, 0.17-0.37]), non-Hispanic Black populations (RERI, 0.36 [95% CI, 0.30-0.42]), and non-Hispanic White populations (RERI, 0.10 [95% CI, 0.09-0.12]). In contrast, positive interactions on the multiplicative scale were found only for non-Hispanic Black populations (ratio of RRs, 1.24 [95% CI, 1.18-1.31]) and non-Hispanic White populations (ratio of RRs, 1.03 [95% CI, 1.02-1.05]), but not for Hispanic populations (ratio of RRs, 0.98 [95% CI, 0.93-1.04]). In the sensitivity analyses using continuous Gini coefficient and social mobility, a positive interaction was observed between higher income inequality and lower social mobility with deaths of despair on both the additive and multiplicative scales for all 3 racial and ethnic groups. This cross-sectional study found that the joint exposure of unequal income distribution and lack of social mobility was associated with additional risks for deaths of despair, suggesting that addressing the underlying social and economic conditions is crucial in responding to the epidemic of deaths of despair.
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