Greg Johnson Case Report and Review of the Literature on Interuterine Myocardial Infarction
Recent cannabis use and myocardial infarction in young adults: a cross-sectional study
Abstract
Groundwork: Cannabis use is increasing amidst immature adults, but its effects on cardiovascular health are poorly understood. We aimed to appraise the clan between contempo cannabis use and history of myocardial infarction (MI) in immature adults (anile 18–44 yr).
Methods: We performed a cross-sectional study using pooled data from the 2017 and 2018 cohorts of the American Behavioral Risk Cistron Surveillance System survey of The states adults. We analyzed the association between whatsoever recent cannabis utilise and history of MI using a weighted logistic regression model that adapted for demographic factors, socioeconomic factors, health-related behaviours, concomitant substance use and other comorbidities. We besides assessed this association afterward stratifying by frequency of use and by primary method of consumption.
Results: Amidst 33 173 young adults (18.v meg weighted), 4610 respondents (3.2 million weighted) reported recent cannabis employ (17.5%, 95% conviction interval [CI] 16.8%–eighteen.2%). A history of MI was more frequent amongst contempo cannabis users (n = 61 of 4610, 1.3%) relative to nonusers (n = 240 of 28 563 [0.8%], adjusted odds ratio [OR] 2.07, 95% CI 1.12–iii.82). A history of MI was associated with cannabis use of more than than 4 times per calendar month (adjusted OR two.31, 95% CI one.18–four.fifty), and with smoking every bit a primary method of consumption (adjusted OR two.01, 95% CI i.02–3.98).
Estimation: Our study provides show supporting an association between recent cannabis utilise and history of MI in young adults. Increasing cannabis employ in an at-adventure population could accept negative implications for cardiovascular health.
Cannabis is one of the most commonly used recreational drugs.1 Recent legalization of cannabis in Canada,2 and decriminalization in multiple jurisdictions in the United States,3 has contributed to its increased availability and social acceptance. Cannabis use is also increasing, particularly amongst young adults (aged 18 to 44 yr).4,5 Furthermore, when comparison prevalence rates earlier and after legalization in Canada, use among young adults increased by a larger amount relative to other age groups.6 Despite the widespread use of cannabis, its effects on health remain poorly understood.
The American Heart Association recently issued a recommendation not to smoke or vapourize whatever production containing cannabis because of its potential damage on cardiovascular health, and chosen for more than inquiry on the epidemiology and trends in cannabis apply among youth and high-risk populations.7 The association betwixt recent cannabis use and stroke has been assessed;8 however, its event on other cardiovascular outcomes remains incompletely characterized. Although heavy cannabis use has been reported to trigger acute myocardial infarction (MI), the electric current testify is express to case–control studies that are decumbent to bias and studies relying solely on administrative data.9–fourteen It is also limited in its definition of exposure, every bit these studies appraise patients with heavy cannabis employ (cannabis abuse or cannabis utilise disorder).9–14 Very few studies have assessed the prevalence of recent cannabis use (whatsoever use within past 30 days) and its association with MI.7,9,15 Prevalence estimates of the main method of cannabis consumption and the frequency of cannabis use are incompletely characterized, and the potential impact of these factors on the gamble of MI remains undefined.
Nosotros aimed to assess the prevalence of recent cannabis use and its clan with history of MI in young adults (aged 18 to 44 yr) in the US, using national wellness survey data.
Methods
Study blueprint and participants
Nosotros performed a cantankerous-sectional study using data collected from two cycles of the annual Behavioral Risk Cistron Surveillance Arrangement (BRFSS), a wellness-related telephone survey conducted by the Centers for Disease Control and Prevention (CDC).sixteen The BRFSS was designed to collect prevalence information on risk behaviours, chronic health conditions and use of preventive services that may touch on health status amidst adults in the The states; it has been shown to produce prevalence estimates with high levels of reliability and validity.17–19 The median response rates for the BRFSS survey were 45.9% for 2017,twenty and 49.nine% for 2018.21
The BRFSS survey consists of a standard set of questions used by all jurisdictions (i.e., states, Commune of Columbia and territories), every bit well every bit optional BRFSS modules and jurisdiction-specific questions. Information on cannabis use is collected equally an optional module, and thus was not available for all jurisdictions. Equally of 2017, the optional cannabis module was expanded to include information on primary method of cannabis consumption. Therefore, for our assay, we pooled data from the 2017 and 2018 BRFSS cohorts, representing 12 jurisdictions in 2017,22 and 16 jurisdictions in 2018.23
We included all respondents aged between 18 and 44 years in this study. Nosotros did not include participants older than 44 years because the BRFSS does not include data on variables that may derange the relation betwixt cannabis use and cardiac outcomes in older patients, such as caste of atherosclerosis, use of lipid lowering or antithrombotic medications and history of peripheral vascular disease. We excluded respondents who were not asked the optional cannabis module, who refused to disclose or were unsure of their cannabis utilise or who had missing demographic, comorbidity or consequence information. The study sample size was adamant by the accomplice, and nosotros did not perform posthoc power calculations.24
We report this study co-ordinate to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline for reporting cantankerous-sectional studies.25
Exposure
The primary exposure for our study was whatever recent cannabis use, categorized as a binary event. In the BRFSS, participants were asked, "During the past 30 days, on how many days did y'all use [marijuana or hashish (2017)] [marijuana or cannabis (2018)]?" We defined whatever contempo cannabis apply as using cannabis i or more than time during the past 30 days.
We also generated a frequency variable for cannabis use, and defined less frequent cannabis apply as 4 or fewer times during the past 30 days (≤ ane fourth dimension per week) and more than frequent cannabis use as more than iv times during the past 30 days (> i time per week). We chose this threshold considering, in our clinical practice, we often encounter patients who swallow cannabis one time a week, and regular, weekly cannabis use has been associated with agin cardiac morphological changes.26 We obtained data on the primary method of consumption (i.east., smoking, vapourization or other forms of consumption) direct from the BRFSS survey. Further details on the variables used to define exposure in our study are found in Appendix 1, bachelor at www.cmaj.ca/lookup/doi/x.1503/cmaj.202392/tab-related-content.
Outcome
The primary outcome was history of MI, which we defined equally a "yes" response to the question: "Has a doctor, nurse, or other health professional ever told you that you had any of the following? … (Ever told) you had a heart attack, likewise called a myocardial infarction?"
Covariates
Covariates included demographic factors (e.1000., sexual activity, race, age), socioeconomic factors (e.chiliad., highest level of education, annual household income), health-related behaviours (e.g., wellness intendance coverage status), concomitant substance apply (east.chiliad., tobacco and alcohol consumption), other comorbidities (e.chiliad., kidney disease, diabetes condition) and jurisdiction-level legalization condition of cannabis (Appendix 1).
Statistical analysis
To address potential selection bias and maintain a representative sample, the BRFSS uses a raking methodology to calculate sample weighting.27 This method incorporates detailed race and ethnicity, regions inside jurisdictions, education level, marital condition, age, gender, homeowner status and telephone source, and reproduces estimates that match national distributions.28 Furthermore, the BRFSS produces prevalence rates that are comparable with other national health surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey.19 Data were stratified and reweighted in accordance with CDC guidelines to reduce nonconvergence and nonresponse bias, and to improve generalizability.29,30 These adjusted sampling weights were used for calculating prevalence estimates of cannabis use (with 2-sided 95% conviction intervals [CIs]).
Our primary analysis was the association between recent cannabis use and history of MI. We used odds ratios (ORs) with 2-sided 95% CIs to express the adjusted treatment issue, which we estimated with a weighted logistic regression model, controlling for all covariates without further covariate selection. Secondary analyses included the assessment of history of MI of contempo cannabis users, stratified by frequency and master method of consumption.
We conducted sensitivity analyses using merely the 2017 BRFSS accomplice with additional aligning for hypertension and hypercholesterolemia; data for these variables were not collected in the 2018 BRFSS accomplice. Additional sensitivity analyses for missing data included a missing category cohort analysis for variables with more than than 5% missing data, and an changed probability weighted analysis for missing exposure data. We performed negative outcome controls to check for bias from residual confounding in our model. We assessed the associations between whatever contempo cannabis use and skin cancer, and recent cannabis use and blindness, every bit negative outcome controls, and expected to observe no clan between these variables.31 Additionally, we performed a confounder analysis to estimate how large an imbalance between the cannabis user and nonuser groups would need to be in the prevalence of cocaine utilise (as an unmeasured confounder) to nullify the association with history of MI (Appendix 2, available at www.cmaj.ca/lookup/doi/x.1503/cmaj.202392/tab-related-content).
We performed a posthoc assay of cannabis use as a continuous variable and its association with history of MI. In addition, nosotros performed a posthoc, propensity-score matched assay of our primary comparison as an alternative method to adjust for confounding. Further details of this analysis are included in Appendix 3, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.202392/tab-related-content. Furthermore, we performed separate posthoc tests for interactions between cannabis utilise and combustible cigarette use, and cannabis employ and due east-cigarette use, with history of MI.
We performed a complete example analysis, and considered a 2-sided p < 0.05 to be statistically significant. We performed all statistical assay using R Software (version 3.6.3).
Ethics approval
The written report protocol was accounted exempt from ethics review, every bit BRFSS data sets are publicly bachelor.
Results
Consummate data were available from 33 173 young adults (xviii.5 one thousand thousand weighted; Figure 1). Of these, 4610 respondents (3.two one thousand thousand weighted; 17.v%, 95% CI 16.8% to 18.2%) reported recent cannabis utilise and 28 563 respondents (15.3 meg weighted; 82.5%, 95% CI 81.vii% to 83.3%) did not report whatever recent cannabis utilise. Compared with nonusers, the prevalence of recent cannabis use was college among males (62.9% 5. 49.3%), unmarried respondents (68.0% five. 46.4%), electric current combustible cigarette users (31.6% 5. xiii.2%), current east-cigarette users (xviii.one% five. v.1%) and heavy alcohol drinkers (17.4% v. 5.2%). Further details on respondent characteristics are reported in Table ane, with a detailed summary of missing data reported in Appendix four, available at world wide web.cmaj.ca/lookup/doi/x.1503/cmaj.202392/tab-related-content.
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Table i:
Respondent characteristics of young adults from the 2017 and 2018 Behavioral Take a chance Factor Surveillance System surveys
Most cannabis users reported frequent cannabis use, defined as more than 4 times during the past 30 days (70.5%, 95% CI 68.three%–72.7%; Tabular array 2). Smoking cannabis was the almost prevalent primary method of consumption (76.iii%, 95% CI 74.3%–78.iv%) relative to vapourization (11.3%, 95% CI 9.eight%–12.eight%) and other forms of consumption, including edibles (12.iv%, 95% CI 10.eight%–13.ix%).
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Table ii:
Characteristics of cannabis employ amid immature adults from the 2017 and 2018 Behavioral Risk Factor Surveillance System surveys
Chief analysis
In our master analysis of recent cannabis employ, assessed every bit a binary effect, a history of MI was reported by 61 of 4610 cannabis users (ane.3%) and 240 of 28 563 nonusers (0.8%) (gamble difference 0.five%, 95% CI 0.2%–0.viii%; unadjusted OR ane.92, 95% CI 1.11–iii.34; adjusted OR ii.07, 95% CI 1.12–iii.82) (Table three and Appendix 5, available at www.cmaj.ca/lookup/doi/x.1503/cmaj.202392/tab-related-content). The association between contempo cannabis utilise and MI was similar in magnitude to associations with MI observed for current tobacco smoking (adjusted OR 2.56, 95% CI 1.56–iv.21) and current smokeless tobacco use (adjusted OR 1.88, 95% CI 1.00–3.fifty) (Appendix 6, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.202392/tab-related-content).
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Table three:
Association between cannabis apply and myocardial infarction among immature adults from the 2017 and 2018 Behavioral Take a chance Factor Surveillance System surveys
Secondary analysis
A history of MI was associated with more than frequent cannabis use (adjusted OR 2.31, 95% CI 1.18–four.50) relative to nonusers. Less frequent cannabis utilise was also associated with an elevated, albeit nonsignificant, odds of history of MI (adjusted OR 1.48, 95% CI 0.52–4.21), relative to nonusers.
Smoking cannabis as a primary method of consumption was associated with a higher odds of history of MI (adjusted OR 2.01, 95% CI 1.02–3.98) relative to nonusers. Similarly, a higher odds of history of MI was observed with vapourization equally a principal method of cannabis consumption (adjusted OR 2.26, 95% CI 0.58–8.82) and other forms of cannabis consumption, including edibles (adjusted OR 2.36, 95% CI 0.81–6.88) when compared with nonusers; however, these were non statistically pregnant.
Additional analyses
The association between recent cannabis utilise and increased odds of history of MI, relative to nonusers, was sustained with additional adjustment for hypertension and hypercholesterolemia, (adapted OR three.54, 95% CI ane.13–11.05) (Appendix 6), and across boosted sensitivity analyses for missing data (adjusted OR i.68, 95% CI 1.01–2.79 in missing category accomplice analysis; adjusted OR 2.04, 95% CI 1.xi–iii.76 in inverse probability weighting analysis). We did not notice an association between recent cannabis utilize and our negative result control variables of peel cancer (adjusted OR i.02, 95% CI 0.59–1.75) and incomprehension (adjusted OR 0.98, 95% CI 0.71–1.35). Furthermore, the results of our confounder analysis advise that the prevalence of cocaine utilise (as an unmeasured confounder) would have to exist implausibly big to nullify the clan with history of MI (Appendix 2).
In a posthoc comparison of cannabis employ equally a continuous variable, the clan betwixt cannabis use and history of MI was i.02 (95% CI 1.00–ane.04) per additional day of utilise inside the final 30 days. The clan betwixt recent cannabis use and history of MI persisted in our propensity-score matched analysis (adjusted OR two.11, 95% CI 1.12–3.97). The posthoc tests for interaction between cannabis utilise and combustible cigarette use, and cannabis use and east-cigarette use, with history of MI were non significant (p = 0.three and p = 0.9, respectively).
Interpretation
We institute show of an association betwixt recent cannabis use and an increased odds of history of MI in a generalizable population of younger adults. This association was stronger amid more frequent users of cannabis. Although a similarly elevated odds of history of MI was observed across methods of recent cannabis consumption, only smoking as a primary method achieved statistical significance.
Our findings add to those of previous studies that take identified an clan betwixt heavy cannabis apply and MI in medical and perioperative settings.7,fifteen,32 Nevertheless, previous studies have relied on a sole assessment of cannabis as a binary exposure in patients with heavy cannabis use (i.e., cannabis corruption or cannabis use disorder). I particular advantage of our analysis was our ability to investigate this association with more granular data related to frequency of cannabis use and method of consumption. Notably, the magnitude of the observed association between cannabis use and history of MI was increased amongst more than frequent users. Moreover, the findings of previous studies may not be representative of immature adults using cannabis, equally they exclusively selected participants within a hospital (noncommunity) setting, and thus may be largely influenced past selection bias or may not accurately reflect the health-related behaviours of members within this cohort. The circuitous sampling design, weighting methodology and external validation of the BRFSS advise that our observed association between cannabis consumption and history of MI may be more generalizable to a broader population of young adults.
The touch of exogenous cannabinoids on the cardiovascular system has been well described.7,33 Afterwards astute exposure, cannabis induces dose-dependent tachycardia and, in some cases, decreased ventricular contractility, palpitations, atrial fibrillation and arrhythmia. Additionally, Δ-nine-tetrahydrocannabinol–mediated activation of the cannabinoid receptor subtype 1 has been shown to increase myocardial oxygen demand, induce platelet activation and crusade endothelial dysfunction.7 In add-on, normal angiography findings are normally observed amongst published cases of acute MI afterward cannabis utilize, suggesting cannabis-induced coronary artery or microvascular vasospasm may reduce claret menstruum to the myocardium later exposure. 34 Frequent and sustained cannabis exposure may contribute to a mismatch between myocardial oxygen supply and demand, and in the context of cannabis-induced myocardial dysfunction and coronary macrovascular or microvascular impairment, may act as a potential mechanism for acute MI. Furthermore, cannabis smoke inhalation has been shown to induce a nearly fivefold increase in carboxyhemoglobin concentrations, and a threefold increase in tar, relative to tobacco fume inhalation.35 Therefore, smoking cannabis every bit a master method of consumption may exacerbate this mismatch between myocardial oxygen supply and demand by reducing oxygen-carrying capacity and impairing myocardial oxygen commitment, potentially leading to MI. However, further enquiry is needed to delineate the mechanism for these associations.
The effect estimates for history of MI were similar across methods of consumption, including amidst people using other forms of cannabis, including edibles, every bit a primary method of consumption. This finding is consistent with a instance study reporting an acute MI triggered after consumption of a lollipop containing a large dose of Δ-9-tetrahydrocannabinol.36 The Canadian authorities recently legalized cannabis edibles;2 however, the risks associated with edibles are poorly understood and are of business organization to Canadian physicians.37 Edibles are often perceived as a safer alternative for cannabis consumption, but recent evidence suggests that edible cannabis is attributed to a larger proportion of cannabis-related emergency section visits for cardiovascular symptoms compared with inhaled cannabis.38 Farther investigation is needed to characterize the mechanism of physiologic and therapeutic effects induced by specific molecules derived from cannabis, and the impact of route of administration on bioavailability.39 Additionally, future studies linking health-related survey and administrative databases,40 or prospectively assessing the impact of cannabinoid use on clinical outcomes, may provide boosted insight on this potential causal relationship.
Limitations
Although nosotros analyzed a nationally representative sample, with granular data regarding cannabis consumption and the ability to control for several of import confounders, the cross-sectional blueprint of the BRFSS meant that nosotros lacked information on the temporal relationship betwixt cannabis utilise initiation and onset of MI. Nosotros were unable to differentiate between participants who began using cannabis before having an MI, and those who began using cannabis later on having an MI. However, the plausibility of our association is strengthened past a similar clan between contempo cannabis use and history of stroke from the same data ready.8 Additionally, MI leading to cannabis use (reverse causation) is unlikely, and the elevated odds observed among more frequent users may provide prove of a biologic gradient for this association. Regardless, health intendance professionals demand to be aware that a relationship between any recent cannabis use and history of MI exists.
Another limitation of our study is potential bias from missing data in our cohort. To address this, we performed 2 additional sensitivity analyses. We observed a consequent association between recent cannabis utilize and history of MI across these analyses, suggesting limited bias due to missing data in our complete case assay.
The retrospective design of the BRFSS may take led to unmeasured confounding in our analysis. Specifically, the BRFSS did not collect information on the use of cocaine and other illicit substances. Notwithstanding, the association between cannabis use and MI has been shown in similar studies that accept been able to adjust for cocaine employ.ten To further assess this problem, we performed a negative outcome control analysis of skin cancer and incomprehension, which suggested limited residual confounding in our model. Our confounder analyses suggested that the prevalence of cocaine use (as an unmeasured confounder) would have to be implausibly large to nullify the association between cannabis use and history of MI.
The BRFSS did not include the chemical limerick and concentration of cannabinoids used by respondents. The chemic limerick of products derived from cannabis varies essentially, and we were unable to determine if our observation could exist attributed to a specific compound or grouping of compounds. Too, cannabis obtained through illegal means may incorporate unregulated, harmful cardiotoxic compounds that may derange our analysis. Laboratory confirmation of cannabis use would provide an ideal measure for our analysis; however, it is non viable to behave such a test at the scale of the BRFSS.
Additionally, the BRFSS did not include data on cardiovascular confounders. The prevalence of many cardiovascular confounders, such as history of peripheral vascular affliction, are depression among immature adults (aged 18 to 44 yr), and substantially increase with older historic period. Nosotros therefore restricted our analysis to young adults to minimize potential bias from the absenteeism of aligning of these confounders.
Lastly, the BRFSS did not collect detailed information on MI, such as type of MI, extent of myocardial necrosis and plasma levels of cardiac biomarkers. This information could exist important for understanding differences in clinical outcomes, and would provide greater insight on the potential mechanism(s) leading to cannabis-induced MI.
Conclusion
Contempo cannabis apply was associated with increased odds of history of MI in young adults (aged 18 to 44 yr). The magnitude of this association increased among more than frequent users of cannabis. The large sample size, generalizability and detailed data on cannabis consumption of this cross-sectional study provide unique insight into this growing public wellness business organization. Further studies and more information are needed to ostend these findings and elucidate the mechanisms contributing to cannabis-associated cardiovascular outcomes.
Footnotes
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Visual abstract available at: https://www.cmaj.ca/lookup/doi/x.1503/cmaj.202392/tab-related-content
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Competing interests: Karim Ladha and Hance Clarke are main investigators of an observational medical cannabis study funded by Shoppers Drug Mart. Subodh Verma is President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician system, and reports research grants and/or speaking honoraria from Boehringer Ingelheim, Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Amgen, Sanofi, Servier, Sunday Pharmaceuticals, HLS Therapeutics, Amarin, Valeant, Bayer, PhaseBio and Pfizer. C. David Mazer reports consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim and Octapharma. No other competing interests were declared.
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This commodity has been peer reviewed.
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Contributors: Karim Ladha, Nikhil Mistry, Duminda Wijeysundera, Hance Clarke and C. David Mazer contributed to the conception and blueprint of the work. All of the authors contributed to data acquisition, analysis and interpretation of data for the work. Karim Ladha, Nikhil Mistry, and C. David Mazer drafted the manuscript. All of the authors revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the piece of work. Karim Ladha and Nikhil Mistry share cofirst authorship.
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Funding: Support for this study was provided in role by Merit Awards from the Department of Anesthesiology and Hurting Medicine, Academy of Toronto (Karim Ladha, Duminda Wijeysundera, Hance Clarke, Gregory Hare and C. David Mazer), an Ontario Graduate Scholarship (Nikhil Mistry), an Endowed Chair in Translational Anesthesiology Research at St. Michael'southward Hospital and the University of Toronto (Duminda Wijeysundera) and a Tier 1 Canada Research Chair in Cardiovascular Surgery (Subodh Verma).
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Disclaimer: The funders had no function in the blueprint, analysis, estimation, preparation, review or approval of the manuscript.
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Data sharing: All information of the Behavioral Risk Factor Surveillance Organization survey are fabricated available by the Centers for Disease Control and Prevention online at: https://www.cdc.gov/brfss/annual_data/annual_data.htm
- Accustomed May 31, 2021.
This is an Open Admission article distributed in accordance with the terms of the Artistic Eatables Attribution (CC BY-NC-ND 4.0) licence, which permits utilise, distribution and reproduction in any medium, provided that the original publication is properly cited, the apply is noncommercial (i.e., enquiry or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
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Source: https://www.cmaj.ca/content/193/35/E1377
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