Cannabis Use Doubles the Risk of CV Death: Meta-analysis

Cannabis use does in fact raise the risk of major adverse cardiovascular events—acute coronary syndromes, stroke, and CV death—a new meta-analysis confirms, though many specifics related to the type and amount of exposure are still elusive.

The study comes at a time when legalization of cannabis, most often for medical purposes, is increasing in both the United States and Europe, Wilhelm Storck, PhD (University of Toulouse, INSERM, France), and colleagues point out in their paper.

Senior author Emilie Jouanjus, PhD, PharmD (University of Toulouse, INSERM), noted that cardiologists and neurologists have long been aware that cocaine and other drugs can cause cardiovascular problems. Potential consequences include developing MI, stroke, cardiomyopathy, and arrhythmias at a younger than typical age. Increasingly, clinicians are realizing that “maybe these pathologies could be due to cannabis” as well, she told TCTMD.

“What we bring with this meta-analysis is we quantify the associations,” said Jouanjus, noting that there are implications for both prevention and management of disease.

Reassuringly, though not surprisingly, the associations between cannabis and CV events are of smaller magnitude than those seen for cocaine and stimulants, she added. The idea with this study is not to demonize cannabis, but “just to make people be aware that there are risks.”

Robert Page II, PharmD (University of Colorado, Aurora), commenting on the study, said that with meta-analyses, like this one, whose associations are derived from observational studies, “ I always caution patients and clinicians [that] I don’t put a lot of faith in the magnitude, but I put a lot of faith in that there’s an issue here.”

The findings offer “a huge signal” and can serve as a useful conversation starter, said Page, who chaired the American Heart Association’s 2020 scientific statement on medical marijuana, recreational cannabis, and CV health.

This latest validation of cannabis’ role as a risk factor for atherosclerotic cardiovascular disease comes on the heels of another study, published last month in JAMA Cardiology, showing how not only smoked marijuana but also THC edibles are tied to endothelial dysfunction, said Page.

It took decades for the world to recognize tobacco’s harms, he added. “If we don’t talk about the risks associated with [cannabis], we’re going to repeat history and it’s not going to be pretty,” given the sheer number of people who’ve begun thinking of cannabis as harmless.

Stanton Glantz, PhD, and Lynn Silver, MD, MPH (both from University of California, San Francisco), also point to the consequences of shifts in thinking amid legalization.

 “Frequent cannabis use has increased in several countries, and many users believe that it is a safe and natural way to relieve pain or stress,” they note in an editorial. “Given the high and growing prevalence of use and especially of frequent use, cannabis has the potential to further aggravate the recent reversal in the historical decline of 60% in US death rates from cardiovascular disease since the 1950s.”

ACS, Stroke, and CV Death

For the meta-analysis, published recently in Heart, the researchers combined data from 24 studies: 17 cross-sectional, six cohort, and one case-control. Mean age across the studies ranged from 19 to 59 years, though users tended to be younger than nonusers, and most of the participants were male. Just one study looked at medical use.

Compared with no use, cannabis exposure was associated with greater risks of ACS (RR 1.29; 95% CI 1.05-1.59), stroke (RR 1.20; 95% CI 1.13-1.26), and cardiovascular death (RR 2.10; 95% CI 1.29-3.42). An analysis restricted to the cohort studies showed similar results.

Plausible mechanisms for these associations include vasospasm, as well as the pleiotropic effects of cannabinoids such as CBD and THC, which work through various pathways. When the type 1 cannabinoid receptor is activated, this can result in “oxidative stress, tissue injury, cell death, proatherogenic, profibrotic, proinflammatory effects and vasodilation/vasoconstriction via the sympathetic nervous system,” they write.  Conversely, activation of the type 2 receptor reduces inflammation and oxidative stress, the researchers explain.

If we don’t talk about the risks associated with [cannabis], we’re going to repeat history. Robert Page II

“These findings should encourage investigating cannabis use in all patients presenting with serious cardiovascular disorders,” Storck and colleagues conclude.

Importantly, among the studies there was no standardized approach to measuring cannabis exposure, Jouanjus highlighted. The meta-analysis was not able to ascertain whether events occurred while participants were active users of cannabis (versus before or after), look for potential differences based on type of use (smoked versus edible), or pinpoint the potency of the cannabis consumed.

Some cannabis products on the market “have a very positive image in the general public, . . . so it’s very important to have information about the risks of smoking cannabis” as well as how these compare to what’s seen with the drug’s other forms, she said.

And, as the editorial notes, other ingredients contained in products that are inhaled or eaten—some of which contain synthetic forms of THC—could have ill effects on cardiovascular health.

“Cannabis use, like tobacco and alcohol use, should be assessed in all patients,” Glantz and Silver urge. “At least in the USA, health professionals are the most influential source of cannabis information regardless of patient age, cannabis use or state legal status, making it important for clinicians to ask about use, educate all patients about cannabis risks and take cannabis use into account in clinical decision-making.”

Page similarly called for awareness across a broader swath of the population, not just among patients who have known cardiovascular disease. “From the standpoint of clinicians, particularly cardiologists, we have to just be asking this at each patient encounter now,” he said.