November 19, 2020

11 min read


Source/Disclosures


Source:
Page RL, et al. Circulation. 2020;doi:10.1161/CIR.0000000000000883.

Disclosures:
DeFilippis, Middlekauff, Rana and Sidney report no relevant financial disclosures. Blaha reports he received research funding from the FDA.

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Marijuana use for recreational and medicinal purposes has increased during the past several years, along with a rise in vaping nicotine products for recreational use and smoking cessation.

The rising use of these products has raised questions about the impact on the heart. Evidence has shown that recreational use of any of these products is not beneficial for the heart, although specific mechanisms behind these effects are still to be determined. Recent studies have determined specific pulmonary effects, particularly with THC-containing e-liquids causing e-cigarette or vaping product use-associated lung injury (EVALI).

“Even if the cardiovascular signal turns out not to be as strong as for pulmonary disease, it is not likely that these behaviors and these products are going to be safe overall,” Michael J. Blaha, MD, MPH, director of clinical research and professor of medicine at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and a Cardiology Today Next Gen Innovator, said in an interview.

In August, the American Heart Association published a scientific statement in Circulation, which stated there is no documented benefit of cannabis use for CVD prevention or treatment. Moreover, the statement detailed preliminary evidence that suggests cannabis use may harm the heart and blood vessels.

AHA scientific statement writing group member Jamal S. Rana, MD, PhD, FACC, chief of cardiology at Kaiser Permanente Oakland Medical Center and adjunct researcher in the division of research at Kaiser Permanente in Oakland, California, told Cardiology Today the statement included the latest available data and addressed the clinical, policy and public health implications of the issue.

Holly R. Middlekauff, MD, from the David Geffen School of Medicine at UCLA, is conducting research on the CV effects of marijuana and vaping.

Source: Isabella Ruedisueli. Printed with permission.

The scientific statement also highlighted the importance of educating the medical community and the public of potential risks of both marijuana use and marijuana vaping, especially as marijuana legalization becomes more widespread in the United States.

“There are growing concerns in the cardiovascular community, particularly in light of expanding legalization of medical and recreational use on the state level,” Ersilia M. DeFilippis, MD, cardiology fellow at Columbia University Irving Medical Center, who with colleagues wrote a review on marijuana use in patients with CVD that was published in the Journal of the American College of Cardiology in January, said in an interview.

“By putting out a scientific statement, the American Heart Association has highlighted that this is a matter of public health importance. We need for cardiologists to have greater exposure to educational programs about marijuana and CVD and disseminate high-quality information to the public, similar to the public health campaigns that have been successful for tobacco smoking,” she told Cardiology Today.

Mixed evidence

Some research to date has associated marijuana use with increased risk for MI in young individuals, in addition to increased risk for arrhythmias, stroke and cardiomyopathy.

“THC can stimulate the sympathetic nervous system, while inhibiting the parasympathetic nervous system, which in turn can cause increased heart rate and blood pressure,” Rana said. “We have seen cases when even young patients present with irregular rhythms such as atrial fibrillation. However, there is a paucity of rigorously performed studies. There remains an urgent need for carefully designed prospective short- and long-term studies regarding cannabis use and cardiovascular safety.”

Several epidemiologic studies have linked nicotine-based vaping with potential CVD, but it has not yet been proven that these products caused the CVD. Some experts have said the data on the association between e-cigarettes and increased risk for MIs and strokes may not be strong enough yet to prove causality.

“I recently reviewed this, and up until a couple of months ago, I could only find about two studies that tried to look at the relationship of e-cigarette use or vaping with heart attacks and strokes,” Stephen Sidney, MD, MPH, director of research clinics for the division of research at Kaiser Permanente in Oakland, California, told Cardiology Today. “They both showed some association of e-cigarette use with these outcomes, but were very poor-quality studies for ascertaining causality, and the reason is that they were both cross-sectional. There is no reasonable evidence about the relationship, or lack thereof, of e-cigarette use with cardiovascular outcomes.”

The AHA scientific statement on marijuana use detailed some potential benefits with marijuana use. For example, known evidence has shown that marijuana can improve pain, reduce nausea and vomiting from chemotherapy and improve epilepsy. Inconclusive evidence is available for Alzheimer’s disease prevention, lower risk for death in HF, protective effects against ischemia/reperfusion injury or improved metabolic profile, among other areas.

Marijuana could interact with CV medications in patients with established CVD, via the cytochrome P450 pathway, DeFilippis and colleagues wrote in the JACC review. As a result, this can increase or decrease the drug levels of CV medications, including statins, anticoagulation, beta-blockers and other antiarrhythmic treatments.

In research of CVD risks associated with vaping nicotine products compared with smoking, led by Holly R. Middlekauff, MD, professor of medicine (cardiology), professor of physiology and assistant dean of student affairs at the David Geffen School of Medicine at UCLA, several signals have indicated that e-cigarettes may alter factors that increase risk for CVD, but potentially not to the extent seen with traditional smoking. In a recent study published in the American Journal of Physiology, these researchers found that prolongation of ventricular repolarization, which is linked to increased risk for sudden death, was increased after smoking a single tobacco cigarette. This increase was greater after smoking tobacco cigarettes compared with vaping, despite similar nicotine levels upon intake.

Jamal S. Rana

Another study, published in the Journal of the American Heart Association in September, reported similar findings regarding immune cell oxidative stress, which can increase risk for atherosclerosis. This study found that tobacco cigarettes increased oxidative stress in immune cells to a greater extent compared to e-cigarettes; nonsmokers had the lowest oxidative stress. Another study published in American Journal of Physiology focused on endothelial dysfunction and found that tobacco cigarette smoking blunted flow-mediated dilation compared with a similar dose of an e-cigarette, which did not. Blunted flow-mediated dilation is a risk factor for atherosclerosis and future CVD risk.

Although these signals are more prominently abnormal in tobacco cigarette smokers, many of the same proposed toxicants are still present in e-cigarette vapers, which may help elucidate how these products might affect patients. “There may be a continuum of risk,” Middlekauff told Cardiology Today. “Tobacco cigarettes are more harmful than e-cigarettes, which certainly are not harmless. It is best not to smoke or vape at all.”

“This is the problem when you’re studying a relatively new product in relatively young people; it takes years to follow them up for heart attacks, so you have to look at very early markers,” Blaha said. “The data from the early markers are pointing in the direction of potential injury.”

The JIVE study, presented at this year’s American Heart Association Scientific Sessions, Blaha added, was an exposure study that assessed blood vessels in young individuals before and after e-cigarette use, and there appeared to be development of endothelial dysfunction in these participants.

Long-term effects

Strong data on the long-term effects of marijuana use and vaping are lacking.

While several studies have shown signals of adverse cardiac outcomes due to marijuana use, most of them are from hospitalized patients, leading to inherent selection bias. Sidney, Rana and colleagues assessed the effects of cannabis use during a 25-year period among participants in the CARDIA cohort who have been followed from young adulthood to middle age (maximum age, 58 years). They reported in the American Journal of Public Health that compared with no use, cumulative lifetime and recent use of marijuana were not associated with incident stroke or TIAs, CHD or CVD mortality.

Despite the growing knowledge about risks of marijuana and vaping — or lack thereof, in some cases — the public, in general, lacks awareness of the CV risks, especially of cannabis. Several studies have shown that children tend to perceive e-cigarettes as safe, especially in social settings. Adults generally understand that e-cigarettes are less harmful than tobacco cigarettes, although may not recognize that they are a potential harmful alternative to complete cessation. The lack of awareness may be a result of the lack of messaging compared with smoking tobacco cigarettes, for example.

Stephen Sidney

“There has been wonderful public health messaging for a long time about smoking, but it is paradoxical that we are sending the message that cannabis is OK because [the U.S. is] legalizing it in many different states now,” Middlekauff said. “Most states now have legalized medical marijuana, and many have legalized recreational use. Many people believe that the government would not legalize something that is bad for you — but of course that’s incorrect, think cigarettes.”

Challenges in research

Although the composition of vaped materials has similarities in the chemical toxin profile compared with tobacco cigarettes, its pattern of use is different. Use can differ by number of puffs, as tobacco smoking involves more frequent puffs, whereas vaping and marijuana smoking require a larger puff and inhaled volumes.

Another difference between vaping and smoking tobacco products is in the patterns users follow. For example, a tobacco cigarette smoker may smoke the same brand of cigarettes every day for years, whereas people who vape will often change products and often use multiple products.

This lack of knowledge may be related to the difficulty in studying these products. For example, vaping marijuana and nicotine products are very different because neither substance is controlled and the contents of each are unknown.

“The challenge with marijuana is also the company it keeps,” Rana said, noting a 2017 report from the National Academy of Sciences, Engineering, and Medicine on the health effects of cannabis and cannabinoids, of which Sidney was an author, concluded that the evidence is unclear as to whether cannabis use is associated with MI and stroke, and the frequent co-use of both marijuana and tobacco combined with the much longer duration and frequency of tobacco smoking than of cannabis smoking for most people made it difficult to assess the independent risk associated with marijuana.

“Gradually, in recent years, we’ve had increasing understanding of the cardiac complications of marijuana, but we still have a lot to learn and a lot of research to do to better understand its effects,” DeFilippis said. “What we do know is that over time, marijuana has become more potent with the increasing use of synthetic cannabinoids.”

“The main concern I have with marijuana is anything you combust and then inhale is a bad thing in general,” Blaha said. “The combustion process of, particularly, tobacco, but other things too, creates free radicals or other potential harmful compounds and fine particle air pollution that when inhaled can cause adverse health effects.”

Michael J. Blaha

Research focus on new ways to address these challenges in studying marijuana use and vaping may provide answers.

“In many ways, like so many things in life, it’s a social experiment going on that’s not necessarily being evaluated as well as it could be,” Sidney said.

Rising use in the young

Use of marijuana and vaping has significantly increased in the younger population in recent years.

The Monitoring the Future Survey has assessed drug and alcohol use in adolescents in the U.S. since 1975. More than 42,500 students from eighth, 10th and 12th grade from 400 schools participated in the 2019 survey. Compared with results from 2018, those from 2019 showed that vaping any kind of material in the month before taking the survey increased from 21.7% to 25% in 10th graders and from 26.7% to 30.9% in high school seniors. This report also found that marijuana vaping increased from 2.6% to 3.9% in eighth graders, from 7% to 12.6% in 10th graders and from 7.5% to 14% in 12th graders.

In contrast, the survey found a downward trend in cigarette smoking, as only 2.4% of 12th graders reported smoking cigarettes daily, whereas 11.7% of 12th graders reported vaping nicotine daily.

“The large number of high school students who vape nicotine is higher than the number that would have used tobacco products before vaping was available,” Middlekauff said. “Many more kids who would not have smoked tobacco products are vaping electronic cigarettes. That’s probably because they think that they’re harmless. Many kids who would have never smoked tobacco cigarettes are vaping, but thankfully, the data show that most are not going on to smoke tobacco cigarettes. Tobacco cigarette smoking amongst teens has never been lower.”

Others believe vaping nicotine is a gateway to smoking tobacco cigarettes in the future.

“I’m a believer that this is true,” Blaha said. “There’s no doubt that, in studies, people who use e-cigarettes are more likely to become smokers than if you didn’t use e-cigarettes at all. Some people say, ‘Some of those people would have become smokers anyway, and they started with e-cigarettes because they’re available, and if e-cigarettes weren’t around, they would have just gone straight to smoking.’ That’s a difficult argument to deal with because you can’t say for sure, but regardless, the outcome is bad if the person became a smoker.”

Blaha added that vaping nicotine can also lead to future dual use of both tobacco cigarettes and vape products.

Cardiologists’ role in cessation

Ersilia M. DeFilippis

The cardiology community can make an impact to increase awareness of specific harms to CV health in helping people quit vaping and marijuana use.

“We know that e-cigarettes and vaping can be harmful to your overall health, lungs and cardiovascular system,” Rana said. “We and the American Heart Association say, ‘Do not be falsely reassured that it’s OK to do the vaping and e-cigarettes. We discourage it absolutely’.”

Discussion about why a patient is using these products can be beneficial — for example, if they are using marijuana to self-manage other con- comitant psychological conditions or for pain management.

“[It’s important] to elicit from our patients why they’re driven to use marijuana. For example, are they self-treating pain or anxiety that can be treated another way?” DeFilippis said. “Even with limited data, we can educate our patients that if they continue to use marijuana, they may be at higher risk for heart attack or stroke.”

Nicotine vaping or e-cigarette cessation may follow the same steps as quitting tobacco cigarettes, which includes group support and pharmacological support with nicotine-replacement therapies or other pharmaceuticals. Of note, it is currently unknown whether these approaches are as effective to quit marijuana use.

E-cigarette use and vaping pose a unique challenge because these products can be used as a bridge to quit tobacco cigarette smoking. Data have shown that e-cigarettes are less harmful than cigarette smoking, but the difficulty lies in the messaging that a patient may be using something less harmful as a way to quit something more harmful.

“We should be asking not just a quick question about smoking, but about everything that the patient is doing behaviorally, including vaping,” Blaha said. “The point is they need to be asking about it, and this is not routine at all.”

More efforts are needed to target young users of marijuana and vaping products, and to educate them on how they can impact CV health. In 2019, the AHA unveiled a new initiative focusing on new research, public advocacy and a youth activation campaign to combat nicotine addiction and e-cigarette use in this younger population.

Cardiologists can also play an important role in educating youth and even the medical community about vaping and marijuana use.

“We need to go out in the community and give talks,” Middlekauff said. “Also targeting primary care, family practitioners, pediatricians, cardiologists from academic centers can get the talking point out there.”

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