Stoned Heart: Can Marijuana give you a Heart Attack?

A 29-year-old male comes to your ED complaining of pressure-like left sided chest pain that started an hour after he smoked marijuana. He has never felt anything like this before. He has no medical problems, surgeries, medications, allergies, and has no family history of heart disease. He does not smoke cigarettes, does not drink alcohol, and has never used cocaine before. Labs and EKG were not done yet, but otherwise his TIMI and HEART score are zero. How would you work up this patient?

When it comes to illicit drugs, cocaine is one of the most well known to have cardiovascular complications, including myocardial infarction, arrhythmias, and cardiomyopathy (1). Marijuana, on the other hand, is thought to be a relatively safe drug that has even been legalized in Alaska, Colorado, Washington, and Oregon.  However, is it possible that marijuana use is not so benign?

Don’t be ridiculous! Stop spreading rumors about Mary Jane!

This post was inspired by a cardiologist who recounted when he was an expert witness in a trial for a patient who had no risk factors for coronary artery disease but had reported regular marijuana use. The lawyer cross-examining him then proceeded to show him case after case of marijuana associated myocardial infarction in reputable journals, dramatically demonstrating to him and the court room an association that he was unaware of at the time. That was my introduction to the topic of marijuana and myocardial infarction as over the next few weeks, I encountered two similar cases of chronic marjiuana smoking young men who suffered myocardial infarctions.

How could marijuana affect the heart?

Marijuana’s main ingredient, THC, exerts multiple, complex effects on the body through the CB1 and CB2 receptors. It increases catecholamines, interferes with peripheral vascular reflex responses, and causes arterial vasospasm, leading to tachycardia, peripheral vasodilation, postural hypotension, and increased myocardial oxygen demand with decreased delivery (2,3).  There is evidence that chronic marijuana use increases carboxyhemoglobin levels (4). Although the data is inconclusive, THC may affect platelet activation and inhibition, through dose-dependent inhibition (5), platelet activation (6), or low dose inhibition but high dose activation (7).  While outside the scope of this review, marijuana use has also been linked to CVAs and limb arteritis, which may further lend credence to a platelet dysfunction theory (8).

Color me intrigued… show me the evidence!

In my review of the literature, the evidence demonstrating a link between marijuana use and myocardial infarction is tepid. The proposed pathophysiology appears sound, but the quality and number of the studies is lacking.

Desbois et. al in 2013 reviewed the literature regarding marijuana and myocardial infarction, finding a total of 147 patients with an average age of 42 years old with a wide range of coronary lesions from normal arteries to widespread atheromas (8). Upon closer inspection, all of the widespread atheromas or two-vessel thrombosis occurred in patients who were at least 35 years old, and all either died or developed angina with marijuana re-exposure. This may indicate pre-existing undiagnosed cardiovascular disease or possibly that long term exposure to marijuana predisposes one to developing these coronary lesions. The majority of case reports did not have any documented cardiovascular risk factors except smoking tobacco. In the few case reports where patients abstained from marijuana after their cardiovascular event, no recurrence was noted, whereas patients who relapsed experienced recurrence during follow up.

A bulk of the cases from the Desbois study came from a case-crossover study by Mittleman et. al that found a relative risk of myocardial infarction of 4.8 within 1 hour after smoking marijuana, which dropped to 1.7 in the second hour after smoking. When other triggering behaviors such as cocaine use or sexual intercourse were removed from the analysis the relative risk dropped from 4.8 to 3.2 (9). In that study, marijuana users were significantly more likely to be obese, current smokers, male, and a minority, but marijuana abstainers were significantly more likely to have hypertension, diabetes, a history of angina, and use either a calcium channel blocker or beta blocker. The inclusion criteria were a limitation of the study as they utilized CK and CK-MB as biomarkers and also required patients to identify the onset and events surrounding their chest pain, opening up the study to recall bias.

On a deeper review of these cases, a trend toward younger patients without significant atheromas starts to emerge. The review also included 3 patients from a case series of 6 unexplained cardiovascular fatalities in Norway with cannabis as the only identifiable toxicological substance in the blood; all of whom had positive serum samples indicating relatively recent exposure.  Their ages ranged from 17 to 43 years old with varying degrees of atheromatosis. All the included patients were over the age of 35, had some degree of coronary artery disease, and evidence of recent infarct. The theory here is that marijuana use triggered their cardiovascular event. Of the three excluded cases, one had a low level of ETOH on board with signs of emphysema, one had signs of a previous infarction but was found dead after his car slid off the road, and one was a 17-year-old who had clean coronaries (2).

Since the Desbois study was released, I found case reports of recurrent ACS and a case of MI, both in young patients with normal coronary arteries (10,11). In the first case, a man in his 40s had two episodes of ischemic sounding chest pain, EKG changes, and positive serum biomarkers with a subsequently normal coronary angiography. In the latter case, a 21-year-old male presented to the ED twice after chest pain developed after playing soccer. His initial visit was treated as musculoskeletal pain and he was discharged. On the second visit, he had anterolateral ST elevations, positive troponins, and was found to have a large LAD thrombus that was treated with aspiration and alteplase. He also had a history of cigarette smoking and labs were significant for moderately elevated lipids and triglycerides.  On follow up angiography, he too had no evidence of coronary artery disease.

Finally, a group of researchers attempted to see if these case reports would demonstrate any epidemiologically significant effect on mortality. They conducted a prospective observational study that followed 2097 patients for 18 years and evaluated marijuana use and mortality after acute myocardial infarction, finding an increased mortality rate for marijuana users that did not reach statistical significance (4). However, due to the low number of patients (109) reporting marijuana use in this study, it was not sufficiently powered to detect a mortality difference.

Final thoughts

As previously stated, the evidence does not clearly support a link between marijuana and myocardial infarction. There are even scattered studies in mice that I did not include here, demonstrating a cardioprotective effect of marijuana. The majority of cases stem from the Mittleman study with all its limitations and the rest are essentially just case reports. However, what is troubling is that the bulk of these cases are young patients without significant coronary artery disease.  Based on these available data, if there is an increased risk, it appears to be greatest within an hour of smoking marijuana and quickly falls after that.

As several states have now legalized marijuana, it will be interesting to see in the coming years if there is any public health impact that can inform our medical decision making. If there is a link between marijuana and myocardial infarction, larger studies will need to be done to detect any mortality differences. Adding another wrinkle to the discussion is the issue of K2, the synthetic cannabinoid. Since it is a cheap street drug, it has become very popular in this region and there are already case reports of K2 associated MI, even in pediatric populations. Based on the formulation, K2 can affect CB1 and/or CB2 receptors with varying degrees of potency. To my knowledge, there is no study investigating whether the strain of marijuana/K2 or its potency at the specific cannabinoid receptor sites plays a role in whether or not patients develop cardiovascular complications from marijuana exposure.

Bringing this back to our case at the beginning, now that you are abreast of the literature surrounding this topic, would your management of that patient change? Would you treat any patient who admits to a history of smoking marijuana differently when they complain of chest pain?

Peer Reviewers: Wendy Chan, MD and Raul Hernandez, MD

Faculty Advisor: Ian deSouza, MD

References

1. Schwartz, B., Rezkalla, S., Kloner, RA, Cardiovascular Effects of Cocaine. Circulation. 2010; 122:2558-2569.
2. Bachs L, Mørland H. Acute cardiovascular fatalities following cannabis use. Forensic Science International [serial online]. January 1, 2001;124:200-203.
3. Thomas G, Kloner R, Rezkalla S. Adverse Cardiovascular, Cerebrovascular, and Peripheral Vascular Effects of Marijuana Inhalation: What Cardiologists Need to Know. American Journal Of Cardiology [serial online]. January 2014;113(1):187-190.
4. Frost L, Mostofsky E, Rosenbloom J, Mukamal K, Mittleman M. Clinical Investigation: Marijuana use and long-term mortality among survivors of acute myocardial infarction. American Heart Journal [serial online]. February 1, 2013;165:170-175.
5. Formukong EA, Evans AT, Evans FJ. The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. J Pharm Pharmacol 1989;41:705–709.
6. Deusch E, Kress H, Kraft B, Kozek-Langenecker S. The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets. Anesthesia And Analgesia [serial online]. October 2004;99(4):1127.
7. Levy R, Schurr A, Nathan I, Dvilanski A, Livne A. Impairment of ADP-induced platelet aggregation by hashish components. Thromb Haemost 1976;36:634–640.
8. Desbois A, Cacoub P. General Review: Cannabis-Associated Arterial Disease. Annals Of Vascular Surgery [serial online]. October 1, 2013;27:996-1005.
9. Mittleman M, Lewis R, Maclure M, Sherwood J, Muller J. Triggering myocardial infarction by marijuana. Circulation [serial online]. June 12, 2001;103(23):2805-2809.
10. SAFAA A. Marijuana-induced recurrent acute coronary syndrome with normal coronary angiograms. Drug & Alcohol Review [serial online]. January 2012;31(1):91-94.
11. Hodcroft C, Rossiter M, Buch A. Clinical Communications: Adults: Cannabis-associated Myocardial Infarction in a Young Man with Normal Coronary Arteries. Journal Of Emergency Medicine [serial online]. November 17, 2013

And now, a song that accurately describes the deleterious effects of chronic marijuana use:

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edenkim

Eden Kim, DO, MPH PGY-3 Emergency Medicine Resident

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