Heavy Marijuana Use Tied to Midlife Cardiovascular Events in U.S. Men With HIV

Heavy marijuana use more than doubled the odds of a cardiovascular event in 40- to 60-year-old men with HIV infection enrolled in the Multicenter AIDS Cohort Study (MACS). The link between heavy marijuana use and cardiovascular disease was independent of viral load, cigarette smoking and other classic cardiovascular risk factors.

Recent research found that 24% to 62% of HIV-positive men who have sex with men (MSM) use marijuana for recreational or medicinal purposes. But little work addresses the long-term consequences of marijuana use in this population. Observational studies report contradictory findings on the impact of marijuana on viral load and CD4 count. A few studies tie marijuana use to myocardial infarction and other cardiovascular events in the general population.

To address these issues, researchers analyzed prospective data from the MACS on how marijuana use affects HIV-related variables and comorbidities in MSM. The MACS is an ongoing observational study in which HIV-positive or negative MSM make study visits twice yearly. The marijuana analysis included two distinct sets of men -- HIV-negative men who became positive while in the MACS (seroconverters) and already HIV-positive men who maintained viral suppression (chronic HIV). The researchers excluded men positive for hepatitis C antibody or reporting one or more years of heavy drug use, except for marijuana.

The MACS team used participant self-report to classify men as heavy marijuana users (daily or weekly use at 50% or more study visits), nonusers (less than monthly or no use) and occasional users (everyone else). They called men moderate/heavy tobacco users if they smoked an average 0.25 packs a day or more. Clinical endpoints were a new AIDS or cancer diagnosis or death after age 30 and a new cardiovascular event after age 40. The researchers used mixed-effects and linear regression models to explore associations between heavy marijuana use and HIV markers or white blood cell (WBC) count. They used Kaplan-Meier and logistic regression analysis to examine the impact of marijuana use on cardiovascular events and other endpoints.

The study population included 182 seroconverters and 376 men with chronic HIV. In the combined groups, median baseline age stood at 40.8 years, 66% of men were white and 79% had more than 12 years of education. Approximately 20% of men reported heavy marijuana use. Heavy marijuana use was associated with cigarette smoking but not with race, education, depression scores, viral load or CD4 count.

Daily marijuana use was associated with lower CD4:CD8 ratio in men with chronic infection but not in seroconverters. Heavy marijuana use had no other associations with viral load or CD4 trajectories or with progression to AIDS, incident cancer or mortality. In both groups of MSM, a higher proportion with heavy marijuana use had a cardiovascular event between ages 40 and 60 years. Among seroconverters, 14.3% of heavy users versus 2.9% of occasional users and 11.1% of nonusers had incident cardiovascular disease, a nonsignificant difference (P = .311). Among men with chronic HIV, 29.2% of heavy users versus 10.9% of occasional users and 6.7% of nonusers had a new cardiovascular event, a highly significant difference (P < .001). Kaplan-Meier curves confirmed a significantly higher cardiovascular event rate between ages 40 and 60 years in heavy marijuana users in the combined study cohorts (P < .001).

Mixed-effects models adjusted for age, race, education, viral load and total cholesterol indicated a significant association between cigarette smoking and higher WBC count (estimate .153, P < .0001). In the same analysis, heavy marijuana use was associated with increasing WBC count in the combined MSM cohorts between ages 40 and 60 (marijuana x age interaction estimate .020, P < .001). Linear regression models confirmed independent associations between heavy marijuana use and increased WBC count (estimate 1.11, P = .01) and between cigarette smoking and increased WBC count (estimate 1.15, P < .0001).

Logistic regression models adjusted for age, smoking, viral load and two to three versus zero to one traditional cardiovascular risk factors linked heavy marijuana use to 2.5-fold higher odds of a cardiovascular event (95% confidence interval [CI] 1.2 to 5.3, P = .016). This model found even higher odds of a cardiovascular event in heavy marijuana users who also smoked cigarettes, compared with users of only one substance (odds ratio 4.8, 95% CI 1.8 to 12.7, P < .01). A separate model determined that the highest quartile of time-updated WBC count (versus the lowest quartile) was associated with 4.3-fold higher odds of a cardiovascular event (95% CI 1.45 to 12.89, P = .009).

This is the first study to link heavy marijuana use to cardiovascular events independently of cigarette smoking and other established risk factors. The authors note that elevated WBC count indicates systemic inflammation and has been tied to higher cardiovascular risk in the general population. They believe these findings "suggest that clinicians should consider heavy marijuana smoking as a modifiable risk factor when optimizing preventive care, particularly for individuals already at increased risk." The researchers propose that identifying heavy marijuana use as a nontraditional cardiovascular risk factor may help explain part of the elevated risk in people with HIV.