Abstract
Introduction:
Observational studies have reported associations between cannabis use and coronary heart disease. Since diabetes is a coronary heart disease equivalent, we hypothesized that cannabis use would be associated with prevalent angina among individuals with diabetes.
Methods:
This analysis included 1314 participants with diabetes (age 47.4±9.0 years, 49.5% male, 28.3% Caucasians) from the National Health and Nutrition Examination Survey years 2011–2018. Cannabis use was self-reported. Prevalent angina was defined by self-reported physician diagnosis. Multivariable logistic regression models were used to examine the association between prevalent angina and cannabis use.
Results:
Approximately 3.3% (n=43) of participants had prevalent angina and 45.7% (n=601) were ever cannabis users. After adjustment, ever cannabis users did not have significantly increased odds of prevalent angina compared with never users (odds ratio: 3.29, 95% confidence interval [95% CI]: 0.88–12.22, p=0.08). However, those who had used cannabis at least once per month for at least 1 year had greater than fivefold increased odds of prevalent angina (odds ratio: 5.73, 95% CI: 1.26–26.04, p=0.03). Current cannabis users had greater than fivefold increased odds of prevalent angina (odds ratio: 5.35, 95% CI: 1.26–22.70, p=0.03), with a dose–response increase based on level of use. Effect modification was present among those with history of cocaine use (interaction p-value <0.001).
Conclusion:
Among individuals with diabetes, cannabis use is associated with prevalent angina with apparent dose response. This finding supports emerging evidence that cannabis may have negative cardiovascular (CV) health effects, and an individualized CV risk assessment should be pursued among those with diabetes.
Keywords: cannabis use, marijuana use, angina, coronary artery disease, cardiovascular disease
Introduction
Cannabis is the most commonly used substance in the United States behind alcohol and tobacco.1 Numerous observational studies have shown associations between cannabis use and coronary heart disease, with a predilection for younger populations.2–4 Cannabis use has also been linked to several other cardiovascular (CV) diseases, including stroke, arrhythmia, peripheral artery disease, cardiomyopathy, and cardiometabolic disease.5 Recent policy changes regarding cannabis legalization for both medical and recreational use have made cannabis consumption almost as conventional as cigarette use.6 Thus, understanding the long-term effects of cannabis, whether harmful or beneficial, is imperative. Despite its prevalence, few studies have examined the longitudinal CV effects of cannabis, especially among groups with elevated baseline risk for CV disease such as diabetes.
Diabetes is one of the most common medical conditions in the United States and a significant cause of overall morbidity and mortality.7 It is also a major risk factor for CV disease7 and is considered a coronary heart disease risk equivalent.8,9 Since cannabis use is emerging as a potential risk factor for CV disease, it would follow that it would also have a deleterious effect on populations with high baseline risk for CV disease. Therefore, we hypothesized cannabis use would be associated with prevalent angina among individuals with diabetes.
Methods
The National Health and Nutrition Examination Survey (NHANES) is a survey of a representative sample of the U.S. civilian population that estimates disease prevalence and overall health. Data from NHANES years 2011–2018 were collected from individuals ages 18–59 through an in-home interview process and subsequent appointments at a mobile examination center. NHANES is a fully public-access and anonymized data set, so no institutional ethics review board approval was sought and no further permissions were required before use.
We excluded participants <18 years of age. Only participants with responses to the cannabis use questions and history of angina questions were included. Age, gender, race (Caucasian, African American, Hispanic, or other), cocaine use, alcohol use, and tobacco smoking status were defined by self-report. Tobacco smoking status was defined as current, past, or never. Cocaine use was defined as ever use. Alcohol use was defined as never, moderate (≤1 drink per day for women and ≤2 drinks per day for men), or heavy (>1 drink per day for women and >2 drinks per day for men). 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 use ≤4 days per month and heavy users were defined as those who reported use ≥5 days per month as has been done in prior studies.10,11 Prevalent angina was defined as an affirmative answer to the question, “Has a doctor or other health professional ever told you that you had angina?” Chronic obstructive pulmonary disease (COPD) was defined as affirmative answers to either of the following questions: “Has a doctor or other health professional ever told you that you had emphysema?” or “Has a doctor or other health professional ever told you that you had chronic bronchitis?”
Diabetes was defined as fasting serum glucose ≥126 mg/dL, hemoglobin A1c ≥6.5%, or use of an antihyperglycemic medication. Hypertension was defined as systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg or use of an antihypertensive medication according to AHA/ACC guidelines.12 Hyperlipidemia was defined as total cholesterol ≥200 mg/dL, serum triglycerides ≥150 mg/dL, low-density lipoprotein ≥190, or use of lipid-lowering medications. Obesity was defined as body mass index ≥30 kg/m2.
Population characteristics were compared based on cannabis use. Continuous variables were reported as mean±standard deviation. Categorical variables were reported as frequency and percentage. A Student's t-test was used to compare continuous variables and a chi-square test was used to compare categorical variables.
Multivariable logistic regression was used to estimate the association between cannabis use and prevalent angina. Two models were used: model 1 was adjusted for age, gender, and race, and model 2 was adjusted for model 1 plus hypertension, obesity, hyperlipidemia, COPD, tobacco smoking status, cocaine use, and alcohol use.
To examine the consistency of the results among subgroups, the association between cannabis use and prevalent angina was evaluated in subgroups stratified by race (Caucasian vs. non-Caucasian), gender, hypertension, obesity, COPD, hyperlipidemia, tobacco smoking status, cocaine use, and alcohol use. The interaction was tested for using variables similar to those in model 2 with addition of the interaction term between ever cannabis use and subgroup stratification. NHANES mobile examination center survey weights were used in all analyses.
All statistical analyses were conducted using RStudio version 1.3.1093 (Boston, MA) and p-values were considered significant if <0.05. All p-values reported are unadjusted.
Results
A total of 1314 participants with diabetes (age 47.4±9.0 years, 49.5% male, 28.3% Caucasians) were included in the analysis. About 3.3% (n=43) of participants had prevalent angina and 45.7% (n=601) were ever cannabis users. Population characteristics stratified by prevalent angina are depicted in Table 1. Those with angina were more likely to be older, white race, obese, and current tobacco users. Those with angina were also more likely to have hypertension, COPD, and hyperlipidemia. Ever cocaine use and ever cannabis use were more common in individuals with angina. Heavy alcohol use was more common in those without angina.
Table 1.
Population Characteristics
| Characteristics |
Prevalent angina
|
p | |
|---|---|---|---|
| Absent | Present | ||
| n (%) | 1271 (96.7) | 43 (3.3) | |
| Age, years, mean±SD | 47.3±9.1 | 51.7±6.8 | <0.001 |
| Men, n (%) | 628 (49.4) | 22 (51.1) | 0.94 |
| Race, n (%) | |||
| White | 351 (27.6) | 21 (48.8) | 0.02 |
| Black | 351 (27.6) | 10 (23.2) | |
| Hispanic | 362 (28.5) | 6 (14.0) | |
| Other | 207 (16.3) | 6 (14.0) | |
| Hypertension | 792 (62.3) | 35 (81.4) | 0.02 |
| Obesity | 831 (65.4) | 38 (88.4) | 0.004 |
| COPD | 115 (9.0) | 15 (34.9) | <0.001 |
| Hyperlipidemia | 907 (71.4) | 39 (90.7) | 0.01 |
| Tobacco smoking status, n (%) | |||
| Past | 279 (22.0) | 9 (20.9) | 0.004 |
| Current | 250 (19.7) | 18 (41.9) | |
| Never | 742 (58.3) | 16 (37.2) | |
| Heavy alcohol use | 671 (52.8) | 19 (44.2) | 0.01 |
| Ever cocaine use | 189 (14.9) | 14 (32.6) | 0.003 |
| Ever cannabis use | 569 (44.8) | 32 (74.4) | <0.001 |
Heavy alcohol use=>2 drinks per day for men and >1 drink per day for women.
COPD, chronic obstructive pulmonary disease; SD, standard deviation.
In a logistic regression model adjusted for demographic and comorbid covariates, ever cannabis use was not associated with increased odds of prevalent angina (odds ratio: 3.29, 95% confidence interval [95% CI]: 0.88–12.22, p=0.08) when compared with never users. Those reporting having used at least once per month for at least 1 year had greater than fivefold increased odds of prevalent angina (odds ratio: 5.73, 95% CI: 1.26–26.04, p=0.03) when compared with never users. Current users had greater than fivefold increased odds of prevalent angina (odds ratio: 5.35, 95% CI: 1.26–22.70, p=0.03) compared with never users. Light users did not have increased odds of prevalent angina (odds ratio: 3.73, 95% CI: 0.77–18.02, p=0.11), whereas heavy users did (odds ratio: 8.00, 95% CI: 1.18–54.28, p=0.04). These results are summarized in Table 2.
Table 2.
Association of Cannabis Use and Prevalent Angina in Diabetics
| Cannabis use | Reference level |
Model 1
|
Model 2
|
||
|---|---|---|---|---|---|
| Odds ratio (95% CI) | p | Odds ratio (95% CI) | p | ||
| Ever user | Never user | 3.94 (1.51–10.32) | 0.007 | 3.29 (0.88–12.22) | 0.08 |
| Every month for ≥1 year | Never user | 5.96 (2.27–15.69) | <0.001 | 5.73 (1.26–26.04) | 0.03 |
| Current user | Never user | 5.97 (1.84–19.42) | 0.004 | 5.35 (1.26–22.70) | 0.03 |
| Light user | Never user | 4.82 (1.24–18.67) | 0.03 | 3.73 (0.77–18.02) | 0.11 |
| Heavy user | Never user | 6.96 (1.69–28.61) | 0.001 | 8.00 (1.18–54.28) | 0.04 |
Model 1 adjusted for age, gender, and race.
Model 2 adjusted for model 1 plus hypertension, obesity, hyperlipidemia, tobacco smoking status, COPD, alcohol use (never, moderate, or heavy), and ever cocaine use.
95% CI, 95% confidence interval.
Table 3 shows the association of ever cannabis users and prevalent angina across subgroups when compared with never users. Significant effect modification was present among those with a history of ever cocaine use (interaction p-value <0.001).
Table 3.
Association of Ever Cannabis Use and Prevalent Angina Among Subgroups
| Subgroup | Angina, n (%) |
Model 1a
|
Model 2a
|
Interaction p-valueb |
|---|---|---|---|---|
| Odds ratio (95% CI) | Odds ratio (95% CI) | |||
| Race | ||||
| Non-White | 22/942 (2.3) | 3.93 (1.29–11.95) | 3.27 (1.05–10.17) | 0.95 |
| White | 21/372 (5.6) | 3.96 (0.98–15.84) | 3.31 (0.39–27.82) | |
| Gender | ||||
| Men | 22/650 (3.4) | 8.14 (2.07–31.94) | 8.81 (1.51–51.55) | 0.09 |
| Women | 21/664 (3.2) | 2.44 (0.60–9.99) | 1.78 (0.15–20.77) | |
| Hypertension | ||||
| Present | 35/827 (4.2) | 4.04 (1.28–12.80) | 3.59 (0.74–17.44) | 0.25 |
| Absent | 7/487 (1.4) | 4.94 (1.10–22.30) | 2.63 (0.06–108.9) | |
| Obesity | ||||
| Present | 38/869 (4.4) | 5.68 (2.34–13.83) | 6.93 (2.37–20.33) | 0.16 |
| Absent | 5/425 (1.2) | 0.96 (0.10–8.83) | 0.03 (0.01–2.29) | |
| COPD | ||||
| Present | 15/130 (11.5) | 0.73 (0.12–4.27) | 0.58 (0.04–9.56) | 0.06 |
| Absent | 28/1184 (2.4) | 10.77 (3.69–31.39) | 8.37 (2.28–30.69) | |
| Hyperlipidemia | ||||
| Present | 39/946 (4.1) | 3.69 (1.38–9.90) | 2.90 (0.73–11.51) | 0.06 |
| Absent | 4/368 (1.1) | 10.60 (0.99–113.00) | — | |
| Tobacco smoking status | ||||
| Current | 18/268 (6.7) | 0.61 (0.11–3.53) | 0.64 (0.14–3.03) | 0.09 |
| Past | 9/288 (3.1) | — | — | |
| Never | 16/758 (2.1) | 6.65 (1.52–28.99) | 9.46 (2.26–39.56) | |
| Alcohol use | ||||
| Current | 36/970 (3.7) | 3.80 (1.19–12.13) | 2.95 (0.66–13.15) | 0.87 |
| Never | 7/344 (2.0) | 3.07 (0.29–32.46) | 9.62 (0.75–124.01) | |
| Cocaine use | ||||
| Ever | 14/203 (6.9) | — | — | <0.001 |
| Never | 29/1111 (2.6) | 3.42 (1.11–10.07) | 3.20 (0.84–12.98) | |
Model 1 adjusted for age, gender, and race.
Model 2 adjusted for model 1 plus hypertension, obesity, hyperlipidemia, tobacco smoking status, COPD, alcohol use (never, moderate, or heavy), and ever cocaine use.
Comparison of ever cannabis users to never users.
Interaction p-value calculated from model 2.
—, Denotes estimates with extreme high values.
Discussion
In this racially diverse and nationally representative population of diabetics, we observed a significant association between cannabis use and prevalent angina after adjusting for traditional risk factors for coronary heart disease. There appeared to be significant effect modification with ever cocaine use, which is a well-documented risk factor for coronary artery disease.13 There also appeared to be a dose–response effect present with increasing amounts of cannabis use.
Cannabis is becoming more accepted among the general population for medicinal and recreational use, so it is critical to recognize its potential public health implications. Its status as a Schedule I drug in the United States makes the use of rigorously controlled trials challenging, so the majority of the data behind its potential health effects are based on weak evidence such as observational studies and case reports.5 The most robust of these data demonstrate a link between cannabis use and acute myocardial infarction.4 Since coronary heart disease is the most common cause of myocardial infarction,14 it would follow that cannabis use would also be associated with coronary heart disease and, consequently, prevalent angina. Our results support this notion and the strong associations we observed suggest that those with diabetes have high susceptibility to this effect. This is no surprise since diabetes is a considered to be a coronary heart disease equivalent,8,9 so these patients are at higher baseline risk for the cardiotoxic effects of this drug.
From a mechanistic standpoint, the cardiotoxic manifestations of cannabis use are thought to be similar to tobacco use since the two substances share many of the same chemical constituents.15 Specifically, similar mechanisms such as increased platelet activation, sympathetic nervous system activation, pro-inflammatory cytokine release, and increased low-density lipoprotein formation are all thought to contribute to its pathogenesis.5 Furthermore, the two substances are frequently used in parallel, so there may also be a component of concurrent toxicity.5 Since diabetes already predisposes the coronary vasculature to a state of accelerated atherosclerosis through disruption of endothelial function, accelerated plaque formation, and increased thrombosis risk,16 the combination of these two factors likely pose an additive or synergistic effect thus leading to the robust associations observed in our study.
Our study suffers from many limitations. The cross-sectional design is subject to residual and temporality confounding. Cannabis use was defined by self-report only and is thus subject to both recall and reporting bias, so the prevalence may be underestimated.17 We also do not have data regarding the route of administration of cannabis, dosage, or periods of abstinence. Cannabis is a heterogenous genus that comes in a variety of potencies, so differential composition may also influence its CV impact.18 In addition, concurrent tobacco use is a potential confounder given its known association with CV disease. Despite these limitations, our study offers a novel link between cannabis use and prevalent angina among participants with diabetes. Other strengths include a racially diverse study population as well as a relatively recent study cohort.
Conclusion
Among individuals with diabetes, there is a significant association between cannabis use and prevalent angina with apparent dose response. This finding supports emerging evidence that cannabis may have negative CV health effects, and an individualized CV risk assessment should be pursued among those with diabetes.
Abbreviations Used
- 95% CI
95% confidence interval
- COPD
chronic obstructive pulmonary disease
- CV
cardiovascular
- NHANES
National Health and Nutrition Examination Survey
- SD
standard deviation
Author Disclosure Statement
The authors whose names are listed certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this article.
Funding Information
Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001420 (Elsayed Z. Soliman). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Cite this article as: Skipina TM, Upadhya B, Soliman EZ (2023) Cannabis use is associated with prevalent angina in individuals with diabetes, Cannabis and Cannabinoid Research 8:4, 679–683, DOI: 10.1089/can.2021.0175.
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