Cannabis use and risk of atherosclerosis cardiovascular disease: a two-sample mendelian randomization study

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Whether cannabis use causally associates with atherosclerotic cardiovascular disease (ASCVD) remains unknown. A genetic approach, using Mendelian randomization principles, can help make inferences on the association between a risk factor and a disease outcome when a clinical trial is impracticable for ethical reasons. Aims To estimate the effect of genetically determined cannabis use on risk of ASCVD, including coronary artery disease (CAD) and acute ischemic stroke (AIS). Methods Using two-sample Mendelian Randomization (MR), 65 independent (R2<0.2) genetic markers associating with "ever use of cannabis" in 184’765 European individuals were employed to estimate the causal association between cannabis use and risk of ASCVD. The genetic instruments were first used to test the causal association between cannabis use and CAD in 60’801 cases and 123’504 controls. Second, we explored the causal association between cannabis use and AIS in 34’217 cases and 406’111 controls. Genetic data for both outcomes predominantly comprised individuals from Caucasian origin. To triangulate genetic findings, we conducted a meta-analysis of observational studies reporting a link between cannabis use and ASCVD, CAD or AIS. Results Based on the genetic analysis, there was no evidence for a causal effect of cannabis use on the risk of CAD (OR=0.97, 95%CI 0.92-1.02, p-value=0.19) or AIS (OR=1.03, 95%CI 0.98-1.09, p-value=0.41). Sensitivity analyses, including MR-Egger, weighted median MR, Steiger filtering and multivariate MR analysis, yielded similar results, and no heterogeneity and directional pleiotropy were observed. Based on the meta-analysis of 6 observational studies for each outcome, ever use of cannabis was not associated with CAD (pooled OR=1.23, 95% CI 0.78-1.69), nor AIS (pooled OR=1.22, 95%CI 0.95-1.50). Conclusion Using a genetic approach recapitulating a clinical trial, we found no evidence in support of a causal effect between cannabis use and CAD or AIS.