TriNetX cohort of 4.6 million shows sixfold MI risk elevation in cannabis users under 50

The retrospective TriNetX analysis examined 4.6 million individuals under age 50 with normal blood pressure, LDL cholesterol, and no diabetes, tobacco use, or prior coronary disease at index. Cannabis users demonstrated hazard ratios of 6.1 for myocardial infarction, 4.2 for ischemic stroke, 2.1 for heart failure, and 3.0 for the composite of cardiovascular death, MI, or stroke. The accompanying meta-analysis pooled 12 studies totaling 75 million participants and yielded a pooled odds ratio of 1.5 for acute myocardial infarction among active users.

Confounding by unmeasured polysubstance exposure remains material; seven of the twelve meta-analysis studies did not record cocaine or methamphetamine use. Prior observational work in the National Inpatient Sample and the Behavioral Risk Factor Surveillance System similarly reported elevated MI odds after adjustment for tobacco but lacked granular cannabis exposure metrics such as THC dose or route. The current data therefore establish association yet leave residual bias from co-ingestants unquantified.

Operationally, the findings support inclusion of cannabis-use queries in cardiovascular risk calculators for adults under 50, comparable to tobacco history. Health systems can embed structured fields in EHR templates to capture frequency and potency, enabling future dose-response analyses. Regulatory labeling requirements modeled on cigarette warnings follow directly from the observed risk elevation in an otherwise low-comorbidity population.

Longitudinal cohorts with biomarker-verified exposure and serial coronary imaging will be required to isolate cannabis-specific mechanisms from residual confounding. ACC guidelines committees are positioned to incorporate these hazard ratios into prevention statements once such data mature.