Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis

Area of Science:

• Neuroscience
• Epidemiology
• Genetics

Background:

• Observational studies suggest a link between substance use disorders and stroke risk.
• The causal relationship and potential confounding factors remain unclear.

Purpose of the Study:

• To meta-analyze observational data on illicit substance use and stroke risk.
• To use Mendelian randomization to assess causal effects of substance dependence on stroke subtypes.

Main Methods:

• Systematic review and meta-analysis of 32 studies (over 100 million participants).
• Two-sample Mendelian randomization using genome-wide association study data for seven drug exposures.
• Analysis of associations with all stroke, ischemic stroke, and hemorrhagic stroke subtypes.

Main Results:

• Meta-analysis showed increased stroke risk with cannabis, cocaine, and amphetamines.
• Mendelian randomization indicated cannabis use disorder is linked to any stroke and large artery stroke.
• Cocaine dependence was associated with cardioembolic stroke and intracerebral hemorrhage; overall substance use disorder increased risk for any stroke and intracerebral hemorrhage.

Conclusions:

• Consistent observational and genetic evidence supports that substance misuse elevates stroke risk.
• Cocaine, amphetamines, and cannabis are particularly implicated in increasing stroke risk.
• Findings underscore the importance of prevention strategies for substance use disorders to reduce stroke incidence.