Abstract Body: Background: Although high opioid-related mortality rates among young-to-middle-aged adults have complicated the interpretation of cardiometabolic disease trends, a US population-based assessment of overlap among risk factors for opioid-related and cardiometabolic disease mortality could clarify the trends.

Methods: We described associations of opioid-related and cardiometabolic disease mortality with respondent characteristics at Wave I in the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative longitudinal cohort of 20,745 US middle to high school students aged 12-19 in 1994-1995. Respondents with missing sampling weights or birthdates were excluded. We identified cardiometabolic disease and opioid-related deaths (definite; probable; suspect) through 12/31/22 using International Classification of Disease (ICD-10) codes (I00-I99 or E00-E88; doi.org/10.17615/zbe9-rh36). We computed cumulative mortality incidence weighted to the source population using life tables. We estimated the relative risk (95% CI) between mortality and baseline demographic, geographic, and behavioral measures (smoking; problem drinking; illegal drug use; substance use among friends; availability of cigarettes, alcohol, and illegal drugs in the home) using contingency tables.

Results: We identified 658 deaths among 18,891 respondents (median age: 43) over 513,368 person-years of follow-up. Cumulative incidence for overall, opioid-related, and cardiometabolic disease mortality was 3.77%, 0.80%, and 0.63%. The relative risk of opioid-related death was higher among respondents at agemedian, 1.58 (0.95-2.62); men, 1.87 (1.10-3.18); nH blacks, 2.01 (1.15-3.51); in the South versus other regions, 1.67 (1.01-2.76); and rural versus urban/suburban areas, 1.47 (0.84-2.59). All behavioral measures were associated with opioid-related mortality and a subset were associated with cardiometabolic disease mortality.

Conclusion: Opioid-related and cardiometabolic disease mortality share several demographic, geographic, and behavioral risk factors, suggesting that opioid-related mortality may be influencing cardiometabolic disease trends in the US population.