People under age 50 who use marijuana are more vulnerable to experiencing adverse cardiovascular events compared with nonusers, according to the results of a large observational study.

“The striking thing is that we found that there were risks in every single cardiovascular endpoint that we looked at: MI, heart failure, all-cause mortality. Everything had a risk, with the highest [being for] MI,” said Ibrahim Kamel, MD (St. Elizabeth’s Medical Center, Boston, MA).

Over a mean follow-up of about 36 months for cannabis users and 44 months for nonusers, the risk ratio (RR) was elevated to 6.18 (95% CI 4.89-7.82) for MI and 4.33 (95% CI 3.41-5.49) for ischemic stroke, Kamel and colleagues report in their paper published yesterday in JACC: Advances. Kamel is also presenting a meta-analysis on cannabis and acute MI risk at next week’s upcoming American College of Cardiology 2025 Scientific Session.

Currently, medical marijuana is legal in 39 US states, three territories, and the District of Columbia, and recreational marijuana use is legal in 24 states and the District of Columbia. With cannabis use becoming more and more commonplace, Kamel said physicians should be asking younger patients about their use of it.

 “Clinicians should understand that this is a risk factor, and they should screen for it, especially if a younger patient is coming from the ER with a cardiovascular concern. [The patient] may not understand that it is a risk factor,” he said. “A lot of times people say no when asked about smoking, but then when you go further and ask them ‘Okay, but are you using cannabis?’ they will say yes.”

Stanton Glantz, PhD, an outspoken critic of the tobacco industry who is now retired from the Center for Tobacco Control Research and Education at the University of California San Francisco, told TCTMD that the findings are similar to a paper they published last year showing that daily cannabis users had higher risks of MI, stroke, or a composite of those two outcomes plus coronary heart disease compared with nonusers.

Glantz said while a few things are unclear in the new analysis, including the types of cannabis products that were used—rolled marijuana cigarettes versus vapes or edibles, etc—the findings are in line with the still-emerging picture of the CV health risks of marijuana.

“For cannabis and heart diseases, the evidence is very clear and consistent,” he said. “Cannabis increases heart disease and myocardial infarction risk, and the effect is independent of cigarette smoking.”

Kamel noted that while they screened out anyone with a cigarette smoking history, users of cannabis may also use cocaine and other substances that were not accounted for in the analysis.

MI, Ischemic Stroke, Heart Failure, Mortality, and MACE

Using the global TriNetX health research network of deidentified electronic health records, the researchers analyzed data on 4,636,628 people aged 50 or younger (mean age 41) who had no significant cardiovascular comorbidities at baseline, normal blood pressure and LDL-cholesterol levels, and no diabetes, tobacco use, or prior CAD.

Approximately 2% of the cohort were cannabis users. Compared with nonusers, those who reported using cannabis had nearly a 15-fold higher prevalence of depressive episodes (P < 0.01) and obesity, defined as body mass index above 30 (P < 0.0001).

In addition to the increased risks of MI and ischemic stroke, cannabis users had higher risks than nonusers for MACE (RR 3.24; 95% CI 2.86-3.66), heart failure (RR 2.02; 95% CI 1.79-2.29), and all-cause mortality (RR 1.50 (95% CI 1.36-1.64).

In Kaplan-Meier analyses, cannabis users had a lower survival probability for all events compared with nonusers (P < 0.0001 for all).

The separate meta-analysis by Kamel and colleagues, which pooled data from 12 published studies, also demonstrated an increased risk of acute MI with cannabis use (OR 1.51; 95% CI 1.12-2.05).

Clinicians should understand that this is a risk factor, and they should screen for it, especially if a younger patient is coming from the ER with a cardiovascular concern. Ibrahim Kamel

While the connection between CV issues and cannabis use is not entirely clear, studies have suggested that it can interfere with heart rhythm, with one small study showing an increased risk of arrhythmias in new users of medical marijuana for chronic pain. It also has been shown to promote endothelial dysfunction, pro-inflammatory cytokine release, and oxidative stress, all of which contribute to coronary microvascular dysfunction and plaque destabilization, Kamel and colleagues say.

To TCTMD, Kamel said he believes the current state of research into cannabis’ health effects is comparable to where research on cigarette smoking was prior to the release of the US Surgeon General’s report that spurred warning labels being added to cigarette packages in 1965.

“Smoking was considered a normal, [even] healthy thing until the studies showed otherwise,” he said. “I think we’re heading that way with cannabis, too. It needs benchwork to understand . . . the actual pathophysiologic mechanisms.”

He added that the ultimate goal would be for cannabis products to carry a warning label—similar to the one on cigarettes—acknowledging health risks that are not fully understood, which he said would be a step toward helping potential users make an informed decision.