Marijuana Use Tied to Heart Failure, MI, Stroke

Daily marijuana use was associated with a 34% increased risk for heart failure within 4 years compared with nonuse, in new observational research.

In a separate study, cannabis use disorder (CUD) was linked with a 20% increased risk for major adverse cardiac and cerebral events (MACCEs) during hospitalization in older patients with cardiovascular risk who were tobacco nonsmokers.

The studies will be presented on November 13 at the upcoming American Heart Association (AHA) 2023 Scientific Sessions.

These were observational data, so they can show only association and not causation, the researchers stress, but they build on other recent findings.

Despite the study limitations, "Is this a signal? Absolutely," said Robert L. Page II, PharmD, MSPH, in an interview with theheart.org | Medscape Cardiology.

Page is a professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of Colorado and chaired the writing group for the 2020 AHA Scientific Statement: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health. He was not involved in either of the current studies.

Marijuana Use and Risk for Heart Failure

Marijuana use in the United States has increased exponentially with increasing state-level legalization, but its effect on cardiovascular health is unclear, Yakubu Bene-Alhasan, MD, MPH, and colleagues write.

In their study, the researchers assessed the association between marijuana use and risk for incident heart failure compared with the risk in nonuse on the basis of survey data and medical records from participants in the National Institutes of Health–sponsored All of Us research program.

They identified 156,999 adults aged 18 years or older who did not have a diagnosis of heart failure at baseline. Participants had a mean age of 54 years, and 61% were women.

About one quarter had hypertension (24%) or hyperlipidemia (23%), 9.2% had type 2 diabetes, and 9% had coronary artery disease (CAD). They had a median body mass index (BMI) of 28; 17% were current smokers, and 22% were former smokers. Almost all had insurance (95%).

On the basis of the participants' reported marijuana use, defined as unprescribed use or use beyond prescribed doses over the previous 3 months, they were classified as never-users (107,976 participants); former users (33,816); or less than monthly (7292), monthly (1686), weekly (2326) or daily (3903) users.

During a median follow-up of 45.3 months, there were 2958 incident heart failure events.

Compared with never-users, daily marijuana users had a 34% increased risk for heart failure after adjusting for age, sex, race, ethnicity, alcohol use, smoking, education, employment, income, health insurance, type 2 diabetes, hypertension, hyperlipidemia, and BMI (hazard ratio [HR], 1.34; 95% CI, 1.04-1.72).

However, after further adjusting for CAD, the risk for heart failure was no longer significant (HR, 1.27; 95% CI, 0.99-1.62), suggesting that CAD is a pathway through which daily marijuana use may lead to this outcome.

"Given that this is an observational study, we can't say that marijuana use causes heart failure," Bene-Alhasan, a resident physician at Medstar Health, in Baltimore, Maryland, told theheart.org | Medscape Cardiology.

Still, "over the years there have been more and more reports of negative effects associated with marijuana use," he noted. "This study and most studies suggest that marijuana use has detrimental effects, especially in the cardiovascular system.

"Given the increasing use of marijuana," he said, "it's something that every physician will come across."

It would be difficult and probably unethical to examine these risks in a randomized controlled trial, Bene-Alhasan said. "But as more and more [observational] studies show association between marijuana and other conditions," he added, "the evidence will be one day overwhelming towards one direction or the other, and then clinicians can make informed decisions with their patients."

Page pointed out that both of these studies show association and not causation, but nevertheless, "these data are a signal of potential cardiovascular issues," he said.

"I don't want people to think, 'Well, if I smoke it once a month I won't have that issue,'" Page said. "Don't get a false sense of security," he warned, because other observational data have show cardiovascular effects even when people were using marijuana weekly.

Other limitations of both studies include that they are abstracts and have not been peer reviewed, he noted.

Of importance, the studies did not distinguish between cannabis smoking or vaping vs edibles. "When you're smoking or vaping a cannabis product," particularly one that is higher in tetrahydrocannabinol or cannabidiol, he said, "you get more acute cardiovascular effects, which you may not see with the edibles."  

CUD and Risk for MACCEs

In a separate report, Avilash Mondal, MD, and colleagues examined the risk for in-hospital MACCEs, defined as a composite of all-cause mortality, acute myocardial infarction (MI), cardiac arrest, or stroke, in older tobacco nonsmokers with established cardiovascular disease (CVD) risk (hypertension, type 2 diabetes, or hyperlipidemia) who had CUD, defined as using cannabis and being dependent on it compared with those without this disorder.  

The investigators analyzed data (including ICD-10 codes) from the National Inpatient Sample (2019) in individuals aged 65 years or older with established CVD risk factors (hypertension, type 2 diabetes, or hypercholesterolemia) when they were admitted to hospital.

Of 10,680,280 patients, 28,535 had CUD; they were generally younger and more likely to be men than were those without CUD. During a median hospitalization of 4 days, 13.9% of the patients with CUD reported MACCE episodes.

Compared with other patients, those with CUD had higher rates of acute MI (7.6% vs 6.0%) and stroke (5.2% vs 4.8%), similar rates of cardiac arrest (1.1% each), but lower rates of all-cause mortality (1.7% vs 3.3%) and dysrhythmia (25.9% vs 34.9%).

Patients with CUD were more likely to have MACCEs (odds ratio, 1.20; 95% CI, 1.11-1.29), after adjusting for baseline demographics, comorbidities, and hospital characteristics.

Study limitations include that the information comes from a national database and that different clinicians may have defined CUD differently, Mondal, a resident physician at Nazareth Hospital in Philadelphia, Pennsylvania, noted in an interview with theheart.org | Medscape Cardiology.

The data did not indicate whether the cannabis was smoked or vaped vs edibles or whether it was medicinal vs recreational, he noted.

Cannabis was legalized in 1996 in California for medicinal use, and then, this was expanded to recreational use, so it "has been in circulation for 20 plus years now," he said, "and now we can see a few of its effects in the older population."

Now that the younger generation is using cannabis more, users need to be more aware of the long-term repercussions on health. There is a lot that is not currently known about cannabis, Mondal said, adding that it would not be ethical to do a randomized trial with cannabis.

Given what is known though, he said, "we as providers — physicians, nurse practitioners — should all be more vigilant" in obtaining information about a patient's cannabis use, when taking their medical history.

"We should be more careful, and ask 'Do you use weed or marijuana? How frequently? Is it medicinal? Why do you use it?'"

About one third of the patients with CUD in this study also had drug abuse. Page observed, which "kind of muddies the water a little," because drugs such as cocaine and methamphetamine can lead to increased risk for atherosclerotic cardiovascular disease (ASCVD).

Nevertheless, both studies add to "the overwhelming evidence that has been generated over the last 5 years that maybe cannabis is going to be a potential risk factor for ASCVD disease or contributing to it," Mondal said.

Cigarette smoking was completely acceptable in the 1940s and 1950s, but how long did it take before it was realized that it led to stroke, heart attack, cancer, he asked rhetorically.

"The latest research about cannabis use indicates that smoking and inhaling cannabis increases concentrations of blood carboxyhemoglobin (carbon monoxide), and tar (partly burned combustible matter) similar to the effects of inhaling a tobacco cigarette, both of which have been linked to heart muscle disease, chest pain, heart rhythm disturbances, heart attacks and other serious conditions," he said in a press release from the AHA.

"Because something is natural doesn't always make it safe," Page added. "There are risks and we're starting to see that. As healthcare providers we need to make sure that patients are aware of that." At the same time, he added, it is very important for clinicians to have a nonjudgmental approach.

The study authors and Page have no relevant financial disclosures.