Cannabis use has risen globally due to expanding legalization and social acceptance, with over 192 million users reported by the United Nations in 2018.1 While it has therapeutic benefits, cannabis consumption has been linked to adverse cardiovascular outcomes, especially myocardial infarction (MI).1,2
Research consistently shows a significant association between cannabis use and acute coronary events, particularly among younger users.1 However, confounding factors like tobacco or established cardiovascular risk factors limit the understanding of cannabis' long-term effects.1, 2, 3 This study aimed to evaluate the long-term cardiovascular effects of cannabis use in relatively healthy individuals.
Methods
Data source
This retrospective cohort study utilized the TriNetX health research network, which aggregates deidentified electronic medical records from health care organizations worldwide. The specific network used for this study was research, which contains data from 53 health care organizations throughout the United States. Given the nature of the study and included date, institutional review board approval was waived.
Study population
Focused on adults aged ≤50 years between 2010 and 2018, divided into 2 cohorts. 1) The cannabis-user group with cannabis use diagnoses (International Classification of Diseases, 10th Revision: F12.1, F12.9, F12.90). 2) The noncannabis-user group. Both cohorts were free of significant comorbidities at baseline, including hypertension, hyperlipidemia or low-density lipoprotein >100 mg/dL, coronary artery disease including prior MI or history of coronary interventions, diabetes mellitus or glycated hemoglobin >7, and tobacco use. The relatively healthy status of these patients was a key aspect of this study design, ensuring that comparisons were not influenced by pre-existing high-risk conditions. Propensity score matching (PSM) was performed; covariates were matched by 1:1 PSM using the greedy nearest neighbor matching algorithm with a cutoff of 0.1 pooled standardized mean difference. The following covariates were included in the PSM: age at index, sex, race, chronic kidney disease, depressive episode, family history of ischemic heart disease, pregnancy, cancer history, creatinine, low-density lipoprotein, glycated hemoglobin, body mass index, and systolic blood pressure.
Study outcome
The primary outcome included MI defined using International Classification of Diseases, 10th Revision codes. Secondary outcomes contained the major adverse cardiovascular events (ischemic stroke, coronary revascularization, and ventricular fibrillation/tachycardia), all-cause mortality, heart failure (HF), and ischemic stroke. The index event was defined as the first time cannabis use diagnosis was detected and, for the nonuser group, was the first office visit.
Statistical analysis
The analysis was performed with TriNetX Live built-in analytics. Continuous variables were expressed as mean ± SD or median (IQR), and categorical variables were presented as numbers (%) where appropriate. Baseline characteristics between the 2 groups were compared by using independent t-tests and chi-square tests for continuous and categorical variables, respectively. Kaplan-Meier (KM) survival analysis was conducted to demonstrate the survival probabilities difference between the 2 groups, with statistical significance assessed using log-rank tests. Cox proportional hazards and logistic regression models were used to estimate HRs and ORs with 95% CIs. The significance threshold was established at P < 0.05.
Results
A total of 4,636,628 relatively healthy adults aged ≤50 years: 93,267 (2.01%) cannabis users and 4,543,361 (97.99%) nonusers. Cannabis users were older (26 ± 8 years vs 21 ± 9.5 years, P < 0.0001) and had higher comorbidities, including a nearly 15-fold higher prevalence of depressive episode (30.63% vs 1.88%, P < 0.01) and body mass index >30 (18.72% vs 3.25%, P < 0.0001). After PSM, each group had 89,776 patients with balanced demographics and baseline health characteristics.
Over 5 years, mean follow-up was 35.7 ± 23.4 months for cannabis users and 44.2 ± 23.8 months for nonusers. MI absolute risk (AR) was 0.558% in cannabis users vs 0.09% in nonusers, with a risk difference (RD) of 0.468% (95% CI: 0.415%-0.52%), a risk ratio (RR) of 6.185 (95% CI: 4.892-7.82), and an OR of 6.214 (95% CI: 4.913-7.86). KM analysis showed lower survival probability in cannabis users (99.119% vs 99.867%, P < 0.0001), with an HR of 7.568 (95% CI: 5.982-9.575).
For ischemic stroke, the AR was 0.405% in cannabis users vs 0.094% in nonusers, with an RD of 0.312% (95% CI: 0.266%-0.358%), an RR of 4.333 (95% CI: 3.419-5.493), and an OR of 4.347 (95% CI: 3.428-5.512). KM survival probability was 99.395% in cannabis users vs 99.866% in nonusers (P < 0.0001), with an HR of 5.151 (95% CI: 4.060-6.534).
Regarding major adverse cardiovascular events, AR was 1.187% vs 0.366%, with an RD of 0.821% (95% CI: 0.74%-0.90%), an RR of 3.24 (95% CI: 2.864-3.665), and an OR of 3.267 (95% CI: 2.886-3.698). KM survival was 98.2% vs 99.495% (P < 0.0001), with an HR of 3.869 (95% CI: 3.42-4.38).
For HF, AR was 0.861% vs 0.424%, with an RD of 0.437% (95% CI: 0.363%-0.511%), an RR of 2.029 (95% CI: 1.795-2.293), and an OR of 2.038 (95% CI: 1.802-2.305). KM survival was 98.763% vs 99.453% (P < 0.0001), with an HR of 2.323 (95% CI: 2.054-2.627).
Regarding all-cause mortality, AR was 1.262% vs 0.841%, with an RD of 0.421% (95% CI: 0.327%-0.515%), an RR of 1.501 (95% CI: 1.369-1.645), and an OR of 1.507 (95% CI: 1.374-1.653). KM survival was 97.96% vs 98.86% (P < 0.0001), with an HR of 1.813 (95% CI: 1.653-1.989) (Figure 1).
Figure 1.
ORs With 95% CIs for Cardiovascular Outcomes in Cannabis Users Compared to Nonusers
MACE = major adverse cardiovascular events; MI = myocardial infarction.
Discussion
This analysis provides evidence linking cannabis use to adverse cardiovascular events, including MI, ischemic stroke, HF, and mortality. Notably, cannabis use appears to pose a substantial and independent risk for these outcomes, even in a population without traditional cardiovascular risk factors. These findings suggest cannabis as a novel and underrecognized risk factor for cardiovascular diseases.
Our study results are consistent with prior research documenting acute coronary syndrome following cannabis use.4 Studies suggest that cannabis use can precipitate MI, particularly within an hour of consumption, with the risk increasing nearly 5-fold.1 This effect is pronounced in young, healthy individuals, who present with chest pain.1,5 Cannabis has also been implicated in endothelial dysfunction, proinflammatory cytokine release, and oxidative stress, all of which contribute to coronary microvascular dysfunction and plaque destabilization.1,2
This study has limitations due to lack of detailed cannabis consumption data and potential misclassification. The inherent limitations of real-world data often result from inconsistent patient reporting in electronic medical records. Future research should investigate the dose-response relationship and the effects of synthetic cannabinoids.
In conclusion, the findings underscore significant cardiovascular risks associated with cannabis use, reinforcing the need for public health initiatives and heightened clinician awareness.
Funding support and author disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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