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The use of cannabis showed a statistically significant association with adverse cardiovascular outcomes independent of tobacco use in a new US study.

However, the study has many limitations, including self-reporting of both cannabis use and cardiovascular outcomes, as well as a cross-sectional design that looks at cannabis use and the history of cardiovascular events at one snapshot in time rather than whether a history of cannabis use is linked to an increase in future cardiovascular events.

In addition, while the data were adjusted for several other cardiovascular risk factors including tobacco use, body mass index, and diabetes, no information was available on the participants' lipid profile or blood pressure.

Despite these limitations, the researchers believe their data suggest that cannabis use may be a risk factor for premature cardiovascular disease.

"Cannabis use has cardiovascular risks. Cannabis is being marketed to the public by industry as a harmless therapeutic, but there are harms related to cannabis use that the public should be aware of," senior author Salomeh Keyhani, MD, professor of medicine at the University of California San Francisco, told theheart.org | Medscape Cardiology.

The authors stress that these findings are important given the increasing use of cannabis in the US population.

The study was published online on February 28 in the Journal of the American Heart Association.

For the study, the researchers analyzed data from the Behavioral Risk Factor Surveillance System, a national cross-sectional survey performed by the Centers for Disease Control and Prevention, that collects information from a representative sample of US adults on risk factors, chronic conditions, and healthcare access. The current study included data collected between 2016 and 2020 from 434,104 individuals aged 18-74 years (mean age, 45 years).

Respondents were asked about their use of cannabis and the number of days of cannabis use in the past 30 days, as well as if they had a coronary heart disease (CHD) diagnosis or had experienced a myocardial infarction (MI) or stroke.

Results showed that 4.0% of respondents used cannabis daily, and 7.1% reported non-daily use (median 5 days per month). The most common form of cannabis use was smoking (73.8% of current users). The prevalence of CHD, MI, and stroke was 3.5%, 3.6%, and 2.8%, respectively.

After adjusting for age, sex, race and ethnicity, educational attainment, tobacco and e-cigarette use, current alcohol consumption, body mass index, diabetes, and physical activity, there was a significant association between daily cannabis use and MI (odds ratio [OR], 1.25), stroke (OR, 1.42), and the composite of CHD, MI, and stroke (OR, 1.28).

There was also a dose-response relationship, with more days of cannabis use per month associated with higher risks.

The association between cannabis use and increased cardiovascular risk was still evident in an analysis that included only those individuals who had never smoked tobacco, with daily cannabis use linked to an increased risk for MI (OR, 1.49), stroke (OR 2.16), and the composite of CHD, MI, and stroke (OR, 1.77).

"We found that, after controlling for potential confounders, cannabis use has a strong independent effect in the general population and a strong association with cardiovascular outcomes independent of the effects of using tobacco cigarettes and e-cigarettes," the researchers concluded. "This analysis is important because it suggests that cannabis use alone may be a risk factor for adverse cardiovascular outcomes," they added.

In terms of possible mechanisms involved, Keyhani suggested that, similar to smoking, inhaling any type of particulate matter can be associated with cardiovascular events. In addition, endocannabinoid receptors are ubiquitous throughout the cardiovascular system, and tetrahydrocannabinol (THC) may have hemodynamic effects, she noted.

She added that the study did not address the safety of cannabidiol (CBD) products.

"In general, I advise my patients to refrain from smoking or vaping cannabis, and if they use edible products, I suggest use of CBD. If they plan to use products with THC, I recommend using products with low THC concentrations," Keyhani said.

Important Data

Commenting on the study for theheart.org | Medscape Cardiology, Robert Page, PharmD, chair of the writing group for the 2020 American Heart Association Scientific Statement on Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, noted that previous studies have suggested links between cannabis use and cardiovascular disease, but there have been some major gaps that this study helps to fill.

One of the outstanding questions relates to whether the association between cannabis use and cardiovascular disease is related to the use of tobacco.

"As many people who use cannabis also smoke cigarettes, it has been suggested that previous studies have just picked up the risk of smoking tobacco and that cannabis is an innocent bystander. But this study has shown an association between cannabis use and increased cardiovascular risk independent of tobacco use," said Page, who is professor of clinical pharmacy, medicine, and physical medicine at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of Colorado School of Medicine, Aurora, Colorado.

The other question the current study has addressed is that of a dose effect, with an analysis suggested increasing risk with increasing use, he pointed out.

"This study certainly has limitations in that it is observational and retrospective, so we can only say it shows an association, and it does not prove a causative link, but I still think these are important data that do show a safety signal with cannabis," Page stated.

"I would consider this study to be a red flag for cannabis, with these findings suggesting it is not as safe as some people might have thought," he added.