To evaluate mortality trends and demographics due to cerebrovascular diseases (CeVD) and psychoactive substance use (PASU) in the U.S. among adults from 1999 to 2023.

PASU may contribute to CeVD, a major cause of mortality and morbidity worldwide, through vascular damage, hemodynamic instability, and behavioral factors.  Despite growing concerns, national mortality patterns of CeVD and PASU in the U.S. remain underexplored.

We extracted mortality data from the CDC WONDER database due to CeVD (I60-I69) and PASU (F10-F19) among adults ≥25 years. We evaluated crude (CMRs) and age-adjusted mortality rates (AAMR) per 100,000, using Joinpoint Regression to calculate annual percent changes (APCs) with 95% confidence intervals (CIs). 

A total of 412,935 CeVD and PASU deaths occurred between 1999 and 2023, especially in Older adults (AAMR: 51.29), with AAMRs rising from 1.68 in 1999 to 10.71 in 2023 [AAPC, 8.127*; 95% CI, 7.466 to 9.564]. The AAMRs decreased from 1999 to 2001 (APC -3.561), followed by a sharp rise till 2004 (APC 49.232*), with a subsequent surge through 2023 (APC 4.009*). Men had higher AAMRs (9.64) than women (4.98), aligning with the overall trends, while male trends declined between 2021 and 2023 [AAPC: Women, 8.711* (95% CI: 8.054 to 10.193); Men, 7.414* (95% CI: 6.762 to 8.974)]. Non-Hispanic (NH) American Indians (AI) had the highest AAMRs (10.59), followed by NH Blacks (8.88), NH Whites (7.33), Hispanics (3.58), and NH Asians (2.12). The Midwest demonstrated the highest AAMRs (8.80), with non-metropolitan areas (9.12) exceeding metropolitan areas (5.89). States showed Oregon (18.19) and California (1.92) had the highest and lowest AAMRs, respectively.

Although the CeVD- and PASU-related mortality rate declined in the early years of the study, rates rose consistently after the mid-2010s. Males, older adults, NH-AI, and the Midwest showed the highest AAMRs, emphasizing targeted interventions to reduce the mortality burden.