Abstract Body: Introduction: Daily cannabis use is now more common than daily alcohol use, but we lack a comprehensive understanding of the association of cannabis use with cardiovascular disease (CVD). We conducted a longitudinal analysis to assess the role of cannabis use associated with mortality, incident stroke, and incident myocardial infarction (MI).

Methods: We included adult patients who received regular care (at least 2 outpatient visits in a 3-year span) from a large Minnesota healthcare system from 2016-2023. The baseline date was defined as the 2^nd qualifying visit, and variables were captured using ICD codes from medical records. Cannabis users were matched with up to four non-cannabis users by age, sex, race-ethnicity, baseline date, and days between the 1^st and 2^nd visit. Outcomes included incident stroke and MI obtained from inpatient admissions and mortality, which was obtained through linkage to state records. We used Cox proportional hazards models to assess the association between cannabis use and each outcome, adjusting for prevalent demographics and comorbidities at the time of the baseline date.

Results: We matched 30,529 cannabis users to 121,623 non-cannabis users, with a mean (SD) age of 36 (15) years, 56% were male, and 71% were White race/ethnicity. During a mean (SD) follow-up of 3.9 (2.4) years, there were 5,425 deaths, 719 incident strokes, and 580 incident MIs (Table). After adjusting for potential confounders and mediators, the use of cannabis was associated with a higher risk of mortality [HR (95%CI): 1.41 (1.32, 1.53)], stroke [HR (95%CI): 1.25 (1.03, 1.53)] and MI [HR (95%CI): 1.53 (1.23, 1.88)] compared to non-users.

Conclusion: Cannabis use was associated with an increased risk of mortality and CVD, even after fully adjusting for potential confounders and other substance use in this general healthcare system population. Given the increasing cannabis use in the US, more research is needed to understand the role of cannabis in CVD pathways and how increasing use alters CVD epidemiology.