Premature mortality from acute myocardial infarction and psychoactive substance use in the United States: An observational trend (1999-2023) and forecasting (2035) study.

BACKGROUND: Acute myocardial infarction (AMI) remains a leading cause of premature death (<65 years) in the United States, with a significant association with psychoactive substance use (PSU). However, long-term trends and future projections of this combined burden remain unclear. METHODS: We conducted a retrospective observational study using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Multiple Cause of Death database to assess premature mortality (ages 25-65 years) related to AMI and PSU from 1999 to 2023. Age-adjusted mortality rates (AAMRs) were derived, and annual percentage changes (APCs) were calculated using joinpoint regression. An autoregressive integrated moving average (ARIMA) model was used to forecast mortality through 2035. RESULTS: From 1999 to 2023, 176,641 premature deaths were attributed to AMI and PSU. The AAMR rose from 1.4 per 100,000 in 1999 to 4.16 in 2023. Mortality increased sharply from 1999 to 2005 (APC 19.04), continued rising through 2021 (APC 2.63), and declined between 2021 and 2023 (APC -9.13). Middle-aged adults (45-65 years) had substantially higher mortality than younger adults (25-45 years) (AAMR 9.63 vs 0.91, 2018-2023). Men had higher mortality than women (6.81 vs 2.53). American Indian/Alaska Native and White populations showed the higher racial burden. Nonmetropolitan areas had markedly higher mortality than metropolitan regions. South Dakota, Kentucky, and Arkansas had the highest state-level mortality. Forecasting predicts only a modest decline to 3.80 per 100,000 by 2035. CONCLUSION: Despite recent declines, premature mortality from AMI and PSU is projected to remain high through 2035, underscoring the need for targeted, evidence-based prevention strategies.