Abstract

Several observational studies have shown that cannabis use has negative effects on the cardiovascular system, but the causality of this relationship has not been confirmed. The aim of the current study was to estimate the effects of genetically determined cannabis use on risk of cardiovascular diseases. Ten single-nucleotide polymorphisms related to cannabis use were employed as instruments to estimate the association between genetically determined cannabis use and risk of cardiovascular diseases using a two-sample Mendelian randomization (MR) method. Summary statistics data on exposure and outcomes were obtained from different genome-wide association meta-analysis studies. The results of this MR analysis showed no causal effects of cannabis use on the risk of several common cardiovascular diseases, including coronary artery disease, myocardial infarction, stroke and ischemic stroke subtypes, atrial fibrillation (AF), and heart failure. Various sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy were observed. After adjusting for tobacco use and body mass index, multivariable MR analysis suggested a causal effect of cannabis use on small vessel stroke (SVS) [odds ratio (OR) 1.17; 95% CI 1.02–1.35; p = 0.03] and AF (OR 1.06; 95% CI 1.01–1.10; p = 0.01), respectively. This two-sample MR study did not demonstrate a causal effect of genetic predisposition to cannabis use on several common cardiovascular outcomes. After adjusting for tobacco use and body mass index, the multivariable MR analysis suggested a detrimental effect of cannabis use on the risk of SVS and AF, respectively.

Highlights

  • In the past 20 years, there has been a rapid increase in cannabis use with the legalization of marijuana in some countries and regions

  • The singlenucleotide polymorphism (SNP) rs4471463 was associated with the smoking status “ever smoked,” rs35053471 was associated with lymphocyte count, and rs73067624 was associated with age-related macular degeneration (PhenoScanner, Supplementary Table 7, Supplemental data)

  • No causal association was observed between cannabis use and risk of any stroke or ischemic stroke subtypes (AS: odds ratio (OR) 1.00; 95% confidence interval (CI) 0.95– 1.06; p = 0.96; any ischemic stroke (AIS): OR 1.00; 95% CI 0.94–1.06; p = 0.91; large artery stroke (LAS): OR 0.95; 95% CI 0.83–1.09; p = 0.45; cardioembolic stroke (CES): OR 0.98; 95% CI 0.89–1.08; p = 0.65; small vessel stroke (SVS): OR 1.09; 95% CI 0.97–1.22; p = 0.14)

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Summary

Introduction

In the past 20 years, there has been a rapid increase in cannabis use with the legalization of marijuana in some countries and regions. Global numbers of cannabis users reached an estimate of 188 million in 2017, which is roughly 3.8% of the global population aged 15–64 years [1]. Several observational studies have suggested that cannabis use is associated with cardiovascular diseases (CVDs), including coronary artery disease (CAD), Cannabis Use and Cardiovascular Diseases myocardial infarction (MI), stroke, atrial fibrillation (AF), and heart failure (HF). Previous studies found that cannabis use independently predicted the risk of acute ischemic stroke among younger adults (adjusted OR, 1.17; 95% CI 1.15–1.20; p < 0.0001) [3] and HF in 18- to 55-year-old individuals (OR, 1.1; 95% CI 1.03–1.18; p < 0.01) [4] compared to non-users using data of the Nationwide Inpatient Sample (NIS) database. Several case reports have described the occurrence of AF following cannabis consumption, suggesting that cannabis use could be a cause of AF [5,6,7]

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