S-EPMC10717446 - Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study. - OmicsDI

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Dataset Information

Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study.

ABSTRACT:

Background

Association between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations.

Methods

Sixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 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.

Results

There 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 was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; OR_pooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; OR_pooled = 1.22, 95%CI 0.95 to 1.50).

Conclusion

Using a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.

SUBMITTER: de La Harpe R

PROVIDER: S-EPMC10717446 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study.

de La Harpe Roxane R Schoeler Tabea T Thorball Christian W CW Thomas Aurélien A Kutalik Zoltán Z Vaucher Julien J

BMC cardiovascular disorders 20231213 1

<h4>Background</h4>Association between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations.<h4>Methods</h4>Sixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute isch ...[more]

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Project description:ImportanceSmoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.ObjectiveTo determine the association between genetic liability to smoking and risk of CAD, PAD, and large-artery stroke.Design, setting, and participantsMendelian randomization study using summary statistics from genome-wide associations of smoking (UK Biobank; up to 462 690 individuals), CAD (Coronary Artery Disease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; up to 60 801 cases, 123 504 controls), PAD (VA Million Veteran Program; up to 24 009 cases, 150 983 controls), and large-artery stroke (MEGASTROKE; up to 4373 cases, 406 111 controls). This study was conducted using summary statistic data from large, previously described cohorts. Review of those publications does not reveal the total recruitment dates for those cohorts. Data analyses were conducted from August 2019 to June 2020.ExposuresGenetic liability to smoking (as proxied by genetic variants associated with lifetime smoking index).Main outcomes and measuresRisk (odds ratios [ORs]) of CAD, PAD, and large-artery stroke.ResultsGenetic liability to smoking was associated with increased risk of PAD (OR, 2.13; 95% CI, 1.78-2.56; P = 3.6 × 10-16), CAD (OR, 1.48; 95% CI, 1.25-1.75; P = 4.4 × 10-6), and stroke (OR, 1.40; 95% CI, 1.02-1.92; P = .04). Genetic liability to smoking was associated with greater risk of PAD than risk of large-artery stroke (ratio of ORs, 1.52; 95% CI, 1.05-2.19; P = .02) or CAD (ratio of ORs, 1.44; 95% CI, 1.12-1.84; P = .004). The association between genetic liability to smoking and atherosclerotic cardiovascular diseases remained independent from the effects of smoking on traditional cardiovascular risk factors.Conclusions and relevanceIn this mendelian randomization analysis of data from large studies of atherosclerotic cardiovascular diseases, genetic liability to smoking was a strong risk factor for CAD, PAD, and stroke, although the estimated association was strongest between smoking and PAD. The association between smoking and atherosclerotic cardiovascular disease was independent of traditional cardiovascular risk factors.

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