We hypothesized that cannabis use is associated with cardiovascular disease (CVD) risk factors. This could explain the reported link between cannabis and cardiovascular events including stroke and myocardial infarction. This analysis included 7,159 participants (age 37.8 ± 12.4 years, 48.6% men, and 61.5% Caucasian) from the National Health and Nutrition Examination Survey years 2011 to 2018. Cannabis use was defined by self-report. Participants with a history of stroke or myocardial infarction were excluded. Composite CVD risk was assessed using the American College of Cardiology/American Heart Association 10-year atherosclerotic cardiovascular risk (ASCVD) score. Participants were classified based on their ASCVD risk levels as low (<5.0%), borderline (5.0% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20.0%). Multinomial logistic regression was used to examine the association between cannabis use and ASCVD risk category using low-risk ASCVD category as the reference level. About 63.9% (n = 4,573) of participants had ever used cannabis. Ever cannabis use was associated with 60% increased odds of high-risk ASCVD score (odds ratio [OR] 95% confidence interval [CI] 1.60 [1.04 to 2.45], p = 0.03). We also observed a dose-response relation between increased use of cannabis and a higher risk of ASCVD. Those reporting ≥2 uses per month had 79% increased odds of high-risk ASCVD score (OR [95% CI] 1.79 [1.10 to 2.92], p = 0.02) and those reporting ≥1 use per day had 87% increased odds of high-risk ASCVD score (OR [95% CI] 1.87 [1.16 to 3.01], p <0.001]. In conclusion, cannabis use is associated with elevated CVD risk. Individuals using cannabis should be screened for CVD risk, and appropriate risk reduction strategies should be implemented.
Despite improvements in atherosclerotic risk factor modification and treatment of clinical atherosclerotic cardiovascular disease (ASCVD), recreational drug use remains one of the key modifiable risk factors. , With a growing prevalence of cannabis use in the young population in the setting of widespread legalization, the importance of risk stratification is paramount. The connection between cannabis use and ASCVD has several proposed pathophysiologic mechanisms including thrombosis, vasospastic and tachycardia-mediated oxygen supply/demand mismatch, , hyperadrenergic state, , and oxidative stress/endothelial injury; all of which are frequently implicated with atherosclerotic cardiovascular events. We hypothesized that cannabis use is associated with cardiovascular disease (CVD) risk factors. We tested this hypothesis using a composite of CVD risk factors assessed using the American College of Cardiology/American Heart Association 10-year ASCVD risk score in the National Health and Nutrition Examination Survey (NHANES).
Methods
The NHANES is a survey of the US population. Data in NHANES were collected from 2011 to 2018 through a series of interviews and evaluations at an independent examination center.
Participants <18 years of age or with a history of myocardial infarction or stroke were excluded from the analysis. Those with any missing data regarding cannabis use, ASCVD components, and any other variables analyzed were excluded. Age, gender, race, tobacco smoking status, and cannabis use were defined by self-report. Ever cannabis users answered affirmative to the question, “Have you ever, even once, used marijuana or hashish?” Users who reported using cannabis at least once per month for a period of at least 12 months answered affirmative to the question, “Have you ever smoked marijuana or hashish at least once a month for more than a year?” Current users listed an integer in response to the question, “During the last 30 days, on how many days did you use marijuana or hashish?” Light users were defined as those who reported using ≤4 days/mo; heavy users were defined as those who reported using ≥5 days/mo. These metrics have been used in previous studies of NHANES. ,
Composite cardiovascular risk was assessed using the American College of Cardiology/American Heart Association 10-year ASCVD score. The ASCVD score is a validated risk assessment tool that estimates cardiovascular risk using a pooled cohort equation that uses age, race, gender, cholesterol, blood pressure (BP), and co-morbidities to provide a 10-year estimate of risk for major cardiovascular events. ASCVD scores were reported as percentages. When modeled categorically, the following risk intervals were used: low (<5.0%), borderline (5.0% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20.0%).
Diabetes was defined as use of an antihyperglycemic medication, fasting serum glucose ≥126 mg/dl, or hemoglobin A1c ≥6.5%. Hypertension was defined as use of an antihypertensive medication or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg according to American Heart Association/American College of Cardiology guidelines. Hyperlipidemia was defined as total cholesterol ≥200 mg/dl, serum triglycerides ≥150 mg/dl, low-density lipoprotein ≥190 mg/dl, or use of lipid-lowering medications. Obesity was defined as body mass index ≥30 kg/m 2 .
Population characteristics were compared based on ever cannabis use. Continuous variables were reported as mean ± SD. Categoric variables were reported as frequency and percentage. Chi-square test was used to compare categoric variables and Student t test was used to compare continuous variables.
Multinomial logistic regression was used to estimate the association between cannabis use and ASCVD score when ASCVD score was modeled categorically; the low risk ASCVD score category was used as the reference level. Because ASCVD score is calculated using age, gender, ethnicity, diabetes status, hypertension status, tobacco smoking status, and hyperlipidemia, these variables were not adjusted for in the regression models. Associations were also measured in subgroups stratified by race, gender, hypertension, obesity, and hyperlipidemia. In the subgroup analyses, a linear regression model was used to test for interaction with the addition of the interaction term between ever cannabis use and subgroup stratification.
All statistical analyses were conducted using RStudio version 1.3.1093 (Boston, Massachusetts) and p values were considered significant if <0.05.
Results
In this analysis, there were 7,159 participants (age 37.8 ± 12.4 years, 48.6% men, 61.5% Caucasian) after exclusions. About 63.9% (n = 4,573) of participants had ever used cannabis. Population characteristics stratified by cannabis use status are shown in Table 1 . Participants who had ever used cannabis were more likely to be male, white, and current tobacco users. Never cannabis users were more likely to have obesity and diabetes. Ever cannabis users had higher mean ASCVD risk scores.
| Characteristics | Cannabis user status | |
|---|---|---|
| n=2586 (36.1%) | n=4573 (63.9%) | |
| Never | Ever | |
| Age (years) | 37.8 ± 12.5 | 37.8 ± 12.3 |
| Men | 1070 (41.4%) | 2411 (52.7%) * |
| White | 1493 (57.7%) | 2907 (63.6%) * |
| Non-White | 1093 (42.3%) | 1666 (36.4%) * |
| Hypertension | 941 (36.3%) | 1693 (37.0%) |
| Obesity | 1135 (43.9%) | 1802 (39.4%) * |
| Diabetes mellitus | 290 (11.2%) | 359 (7.9%) * |
| Total cholesterol (mg/dL) | 187 ± 40.3 | 188 ± 42.6 |
| LDL (mg/dL) | 112 ± 34.8 | 111 ± 34.9 |
| HDL (mg/dL) | 53.4 ± 15.7 | 53.4 ± 16.0 |
| Current tobacco smoker | 275 (10.6%) | 1585 (34.7%) * |
| ASCVD risk score (%) | 3.0 ± 4.1 | 3.6 ± 4.6 * |
⁎ p <0.05 compared with never users. LDL = low-density lipoprotein; HDL = high-density lipoprotein; ASCVD = atherosclerotic cardiovascular disease; Obesity = body mass index ≥ 30 kg/m 2 .
Table 2 shows the results of the multinomial logistic regression. Ever cannabis use was associated with increased odds of borderline (odds ratio [OR] (95% confidence interval [CI] 1.51 [1.23 to 1.84], p <0.001), intermediate (OR [95% CI] 1.49 [1.26 to 1.78], p <0.001), and high (OR [95% CI] 1.60 [1.04 to 2.45], p = 0.03) ASCVD scores (reference group: low ASCVD score). Current cannabis use was associated with increased odds of borderline (OR [95% CI] 1.32 [1.01 to 1.72], p = 0.04) and intermediate (OR [95% CI] 1.37 [1.09 to 1.73], p = 0.007) ASCVD scores (reference group: low ASCVD score). Current cannabis use was not associated with increased odds of high (OR [95% CI] 1.41 [0.80 to 2.51], p = 0.24) ASCVD scores (reference group: low ASCVD score).
| Cannabis use | Reference level | ASCVD risk category | ||
|---|---|---|---|---|
| Borderline OR (95% CI) | Intermediate OR (95% CI) | High OR (95% CI) | ||
| Ever user | Never User | 1.51 (1.23-1.84, p<0.001) | 1.49 (1.26-1.78, p<0.001) | 1.60 (1.04-2.45, p=0.03) |
| Current user | Never User | 1.32 (1.01-1.72, p=0.04) | 1.37 (1.09-1.73, p=0.007) | 1.41 (0.80-2.51, p=0.24) |
| Every month for ≥ 1 year | Never User | 1.73 (1.38-2.16, p<0.001) | 1.96 (1.62-2.37, p<0.001) | 1.87 (1.16-3.00, p=0.01) |
| ≥ 2 uses per month | Never User | 1.78 (1.43-2.23, p<0.001) | 1.90 (1.56-2.30, p<0.001) | 1.79 (1.10-2.92, p=0.02) |
| ≥ 1 use per day | Never User | 1.72 (1.38-2.16, p<0.001) | 1.94 (1.60-2.35, p<0.001) | 1.87 (1.16-3.01, p<0.001) |
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