To our knowledge, this is the largest population-based analysis to date reporting the burden and impact of CUD+ on HC and associated in-hospital outcomes in young adults using the nationwide cohorts in the US. Among the total hospitalizations in this age group, 3.2% were CUD-related admissions. This study revealed higher odds of HC in overall young population (aOR 1.22) and young adults with known benign hypertension (aOR 1.17) when adjusted for comorbid conditions, tobacco use disorder and alcohol abuse. Furthermore, the higher risk still persisted in overall young adult hospitalizations even after additional adjustment with cocaine abuse and stimulant use but young adults with known benign hypertension showed non-significantly higher odds of HC.

Unmatched CUD+ cohort often consisted of males (61.2% vs. 25.5%), blacks (29.0% vs. 18.8%), Medicaid enrollees (49.9% vs. 39.2%) and patients from the lowermost income quartile (40.8% vs. 31.8%) consistent to recent data from the 2015 National Survey that showed that individuals in poverty were three times more likely to suffer from CUD after controlling for gender, age, tobacco, and alcohol use [9]. Tobacco use, alcohol, drug abuse, depression, psychosis, history of previous myocardial infarction, valvular heart disease, chronic pulmonary disease, pulmonary circulation disease, and liver disease were more prevalent in CUD+ cohort than CUD- cohort.

The crude prevalence of the HC was higher in the CUD+ cohort as in comparison with the CUD- cohort. Similarly, when adjusted for demographics, hospital characteristics, and comorbid conditions, our analysis revealed higher odds of HC admission with CUD+. Available evidence on the effects of cannabis on blood pressure appears to be conflicting. Courts et al. reported that synthetic cannabinoid toxicity in young males is connected to cardiovascular symptoms, including tachycardia and hypertension [4]. In a study using a cross-sectional national survey, Vidot et al. reported that cannabis users had a higher prevalence of hypertension than non-users, especially heavy users having 80% higher chances of hypertension [10]. In addition, Yankey and colleagues concluded, with similar national outpatient data, that increase in marijuana use each year was not only significantly associated with hypertension but with metabolic syndrome as well [11]. In addition, Fong et al. reported a 1.6-fold increase in malignant hypertension among individuals with CUD and a rising trend in the frequency of admissions between 2007 and 2014, especially among young patients (18–44 years) with CUD+ compared to elderly patients [3]. Adrenergic stimulation, alongside parasympathetic nervous system inhibition, causing a positive chronotropic effect, vasoconstriction, and increased blood flow might be the best plausible explanation of hypertension in cannabis users [12,13]. On the other spectrum of HC+ and CUD+ relation, Spindle et al. recounted acute effects of cannabis in healthy infrequent-cannabis users as a transient increase in heart rate and a significant decrease in systolic BP with 10 mg of smoked cannabis [14]. In the elderly (with mean age of 70 years), a reduction in 24 h systolic and diastolic BP has been demonstrated after cannabis use [15]. In another large-population observational study, Haleem et al. showed no association between hypertension and cannabis use [7].

In this study from 2015 to 2017, the propensity matched CUD+ cohort admitted for HC consisted of a higher proportion of black patients (64.8%), and patients with a greater prevalence of smoking, alcohol, and drug addiction vs. CUD- cohort. Consistently, Kennedy et al. from a national survey revealed that African American young adults were more likely than whites to use cannabis before tobacco [16]. In an NHANES survey, non-Hispanic white people (55.7%) had considerably higher hypertension control rates than non-Hispanic black adults (48.5%), non-Hispanic Hispanic (43.5%), and Hispanic (47.4%). Furthermore, concomitant substance abuse may play a vital role in predicting the risk of future cardiovascular events in young adults with CUD+. Prior reports suggested a link between cigarette smoking and earlier onset and increased frequency of cannabis use, as well as a higher incidence of cannabis use disorder symptoms [17]. The combination of both alcohol use disorder and CUD+ was linked to heavier drinking habits and more marijuana difficulties than each substance’s disordered use alone [18].

Our propensity-score matched analysis showed a higher rate of comorbidities such as prior myocardial infarction, chronic pulmonary, liver disease, depression, and psychosis in HC + CUD+ admissions. Cannabis usage was linked to the prevalence of coronary artery disease, after accounting for established cardiovascular disease risk variables, in a national survey (2011–2018) [19]. Recent studies show that CUD+ is associated with depression, especially in young men during adolescence, while the depression is stronger in women during midlife [20]; serotonin may mediate a potential genetic correlation between CUD+ and major depression [21]. Forti et al. conducted a multi-center case–control study and found that daily use of high-potency cannabis can raise the risk of a psychotic disorder by up to five times [22]. Independent association of cannabis use with increased risk of arrhythmias has been reported in young adults with comorbid depression, however, data remains limited to define the long-term effect of depression and cannabis use on systolic or diastolic blood pressure [23]. A study on the elder population reported a greater risk of respiratory symptoms and chronic obstructive pulmonary disease (COPD) when smoking both tobacco and cannabis than tobacco alone [24]. Contrary to this, Gunasekaran et al. reported cannabis users had statistically significantly lower odds of in-hospital mortality in cannabis users than non-cannabis users, among hospitalized COPD patients [25]. Meanwhile, Adejumo et al. showed that cannabis use is associated with decreased incidence of liver disease in alcohol users [26]. Our study revealed lower rates of DM, PVD, hyperlipidemia, obesity, and renal failure in the CUD+ cohort.

Hypertensive crisis significantly increases the long-term risk of other acute cardiac events as established in a 10-year follow-up study by Lee and colleagues [27]. Therefore, it is important to evaluate the risk of major cardiac events in HC patients admitted with known CUD. In the adjusted multivariable analysis, we found significantly higher odds of all-cause mortality by 5.7 folds, the arrhythmia by 1.7 folds, and stroke by 1.4 folds in the CUD+ cohort admitted for HC compared to CUD- cohort. These results are consistent with previous studies showing an association of cannabis use with increased burden and risk of cardiac arrhythmias [28], including atrial fibrillation, atrial flutter, atrioventricular block, premature ventricular contractions, premature atrial contractions, ventricular tachycardia, and ventricular fibrillation that can be life-threatening. Our previous analysis has also confirmed the role of cannabis in higher correlation with arrhythmia and stroke irrespective of concomitant substance abuse [29]. A systematic analysis by Richards et al. highlighted the cannabis-associated increased risk of both acute coronary syndrome and chronic cardiovascular disease [30]. Endocannabinoids are detected in heart tissues and are suggested to be involved in the regulation of heart rate and blood [31]. Though our study did not show statistically significant acute myocardial infarction and cardiac arrest in CUD+, it did show higher odds for these events in CUD+ cohort without reaching a statistical significance. In our previous studies using the National Inpatient Sample and Behavioral Risk Factor Surveillance System (BRFSS) database from the CDC, we observed rising trends and positive associations of cannabis use with stroke events in young adults [32,33]. This is thought to be multifocal angiopathy in young individuals [34] or a cannabis-related consequence of arterial obstruction from a post-myocardial infarction left ventricular thrombus [35]. Though the frequency of tobacco use disorder, alcohol abuse, depression, history of previous myocardial infarction, valvular heart disease and pulmonary circulation disease were higher in HC hospitalizations for CUD+ cohort than CUD-, these comorbidities were not independently associated with higher MACCE in CUD+ compared to CUD-. As a result, according to our population-based study, these characteristics do not appear to operate as effect modifiers for HC-related MACCE for cannabis use status. The risk of the composite endpoint of major adverse cardiac and cerebrovascular events when controlled for confounders trended higher but did not reach a statistical significance (adjusted OR: 1.16, 95% CI: 0.91–1.47, p = 0.231).

This study has some limitations that should be considered while interpreting its results. First, there is a possibility of ICD-10 coding error and selection bias as the NIS is an administrative dataset even with the use of validated codes. Additionally, due to the retrospective nature of the dataset, we could not assess the duration, mode, and dose of administration, frequency of cannabis use, or specific cause of death. Moreover, anti-hypertensive medication history of the patients was not available in the NIS. The severity of HC events was not reported. However, this study offers the first perspective into this understudied subject using a large nationwide cohort and invites future prospective studies to further evaluate the association of CUD+ with HC and subsequent short-term risk of MACCE.