Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study

Abstract BackgroundResearch on the link between cannabis use and the development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations. AimsTo estimate the effects of genetically indexed cannabis use on the risk of coronary artery disease (CAD) and acute ischemic stroke (IS). Methods65 independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use (n=184,765), were employed as instruments to estimate the association between genetically indexed cannabis use and risk of CAD and IS using a two-sample Mendelian Randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D Consortium; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results. ResultsThere was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy were observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k=6 studies; ORpooled=1.23, 95% CI 0.78 to 1.69), nor with IS (k=6 studies; ORpooled=1.22, 95% CI 0.95 to 1.50). ConclusionUsing a genetic approach approximating a clinical trial revealed no evidence for a causal effect of genetic predisposition to cannabis use on CAD or IS development. These findings are reassuring from a public health perspective, as ever cannabis use is unlikely to contribute to the risk of ASCVD.