By Rebecca L. Fahey, MD, PhD, MBA
Integrative Medicine Epidemiologist, Wheeling, WV
Dr. Fahey reports no financial relationships relevant to this field of study.
SUMMARY POINTS
- This study found no evident association between cannabis use and stroke, including stroke before 45 years of age.
- Tobacco smoking showed a clear, dose-response shaped association with stroke across multivariable models.
SYNOPSIS: No associations between cannabis use in young adulthood and strokes later in life were found in multivariable models. An almost doubled risk of ischemic stroke was observed in those with cannabis use > 50 times; this risk was attenuated when adjusted for tobacco usage. Smoking ≥ 20 cigarettes per day was clearly associated both with strokes before 45 years of age and with strokes throughout the follow-up.
SOURCE: Falkstedt D, Wolff V, Allebeck P, et al. Cannabis, tobacco, alcohol use, and the risk of early stroke. A population-based cohort study of 45,000 Swedish men. Stroke 2017;48:265-270. doi: 10.1161/STROKEAHA.116.015565.
Stroke is a prominent global public health problem and its increasing incidence in young adults is alarming. It is the third leading cause of death in developed countries.1 The total number of people having a stroke every year has increased because of the improvement of acute stroke care, and more people are living with the devastating after effects.1 Increasing evidence has shown that diet and lifestyle changes can decrease the modifiable risk factors of stroke by more than 90%.1
These modifiable risk factors (tobacco, alcohol, poor diet, sedentary lifestyle, hypertension) appear in late adolescence, allowing for early intervention and prevention opportunities.2 Falkstedt et al found a noteworthy connection between cannabis and tobacco use in a recent study. A small number of cases of stroke occurred among men who mainly smoked cannabis and who reported occasional tobacco or alcohol use. Despite reports linking cannabis to cerebrovascular effects that could lead to stroke, there is a lack of epidemiological evidence to support these claims.3 Most of the strokes occurred in chronic cannabis users who also mixed it with tobacco or smoked tobacco after smoking cannabis.3 Most of the current information available on the association of cannabis and stroke comes from clinical reports and retrospective studies. The association of stroke and cannabis use has been examined in the literature, but separating the risk of stroke from cannabis as opposed to tobacco, alcohol, cocaine, and amphetamines has been difficult.4
With the increasing legalization of cannabis around the world and the large number of individuals estimated to be using the drug, about 180 million annual users,5 it is imperative to encourage more longitudinal and prospective studies on cannabis users. In this population-based cohort, Falkstedt et al examined a survey of 49,321 Swedish men who had enlisted in military service between 18 and 20 years of age, along with a two-day medical and psychological screening. These men also completed two questionnaires examining social and behavioral aspects of substance use.
The authors recorded the quantities of exposure to cannabis, alcohol, and tobacco. A thorough baseline was established by recording baseline health data on these men: height, weight, blood pressure, body mass (calculated), cardiorespiratory fitness levels, current medical diagnosis, educational level (estimated), parental history of CVD, and socioeconomic status during childhood. Stroke incidences for these individuals between the ages of 29 to 59 were followed from 1971 to 2009 using the National Hospital Discharge Register.
The Cox proportional-hazards regression was used to examine cannabis use in young adulthood as a possible risk factor for all strokes until 59 years of age. Hemorrhagic strokes associated with cannabis use and strokes occurring before 45 years of age were examined without dividing them into stroke type because of the low numbers. Ischemic strokes were examined separately. After crude models were computed, three models were estimated: 1) body mass index, cardiorespiratory fitness, migraine, diabetes mellitus, and early parental CVD; 2) socioeconomic status in young adulthood; and 3) tobacco and alcohol use. Analysis was performed by SAS version 9.4 for Windows.
Within the cohort follow-up period until 59 years of age, there were 1,037 first-time strokes (48% ischemic, 23% hemorrhagic), and before 45 years of age, there were 192 first-time strokes (40% ischemic, 27% hemorrhagic). Interestingly, cannabis use had no association with stroke before 45 years of age found in multivariable models: cannabis use > 50 times (hazard ratios [HR], 0.93; 95% confidence interval [CI], 0.34-2.57). Alcohol and tobacco use showed clear dose-response associations with stroke before 45 years of age. (See Table 1.) There was no significant association between cannabis use in young adulthood and overall incidence of stroke until 59 years of age (HR, 0.95; 95% CI, 0.59-1.53). Clear, dose-response association was demonstrated between cigarettes smoked and stroke (HR, 5.04; 95% CI, 2.80-9.06), and with strokes throughout the follow-up (HR, 2.15; 95% CI, 1.61-2.88). A link between alcohol use and stroke was suggested by crude models (HR, 1.56; 95% CI, 0.60-4.03) and adjusting for alcohol and tobacco use (HR, 1.39; 95% CI, 0.91-2.13), none of the cannabis groups showed an increased hazard of stroke.
Table 1: Pooled Results for Adjusted HR for Cannabis, Tobacco, and Alcohol Consumption |
||
|
Stroke < 45 y of Age |
Hazard ratio |
95% CI |
|
Cannabis > 50 times |
0.93 |
0.34-2.57 |
|
Smoking tobacco > 20 cigarettes per day |
5.04 |
2.80-9.06 |
|
Alcohol > 25 drinks per week |
1.56 |
0.60-4.03 |
COMMENTARY
According to the Global Burden of Disease 2010 study, worldwide age-standardized stroke mortality has decreased over the last two decades; however, deaths and disability from stroke are increasing.1,6 This means the number of individuals who survive stroke and live with disability is increasing.2 Cigarette smoking showed a clear dose-response relationship with increased stroke risk, while the authors found no clear association between cannabis and stroke risk. They were unable to confirm previous research4,8 on the increased risk of stroke with cannabis consumption. Few cases of stroke were reported in this study among heavy users of cannabis who only used tobacco and alcohol sparingly. In addition, the authors had difficulty controlling for confounding variables, such as separating tobacco and alcohol users from those who used only cannabis.
This speaks more of the importance, as emphasized by the World Health Organization, on the growing use of cannabis around the world4 and the co-use of cannabis and tobacco. Hemachandra et al performed a cross-sectional study, based on self-reported data, and did not differentiate the amount of tobacco smoked.9 Westover et al found an increased risk of ischemic stroke with cannabis use and an even bigger risk with tobacco.10 Research has shown that more than 90% of the disabilities caused by strokes are attributable to modifiable risk factors: smoking tobacco, alcohol consumption, unhealthy diet, sedentary lifestyle, and hypertension.6 These modifiable risk factors may be present as early as late adolescence and clearly represent a public health problem.1
The scope of global stroke epidemiology is shifting.1 Increasing clinical,11 retrospective, and case studies have linked smoking cannabis to stroke, especially in people younger than 45 years of age.5 Marijuana is the most commonly used illegal drug in the world.6 Interestingly, most cannabis users consider smoking marijuana to be relatively harmless to their health. They also routinely mix cannabis with tobacco and smoke them together7 or smoke a cigarette after smoking cannabis.8 This complicates the research on cannabis and stroke. It is a well-known fact that smoking tobacco has been linked to stroke. The relationship between cannabis and stroke is multifaceted and includes many confounding variables, such as smoking tobacco and consuming other drugs, including alcohol, while smoking cannabis.9 Heavy alcohol consumption has been shown to increase the relative risk of stroke, while low or moderate consumption has been shown to be protective.12 Many studies have shown the effect of cannabis on the cardiovascular system and the risk of cerebrovascular complications.13
Despite the research linking cannabis with stroke, it has been difficult to separate cannabis from these confounding14 factors, and very little epidemiological data have been produced in support of it.3,17 The case reports that link cannabis to acute strokes11 and ischemic strokes16 have shown a clear indication that more research is needed in this area.11 More research is needed on the mixing of cannabis with tobacco and smoking them together, too.18 In the future, more epidemiological evidence, in the form of prospective studies examining the link between cannabis and stroke, is needed to establish a clear risk of stroke in cannabis smokers.19 More evidence is needed to prove cannabis independently affects stroke.10,16
Recommendations include increasing longitudinal epidemiological prospective studies on all groups of cannabis smokers17 because of the growing popularity of cannabis inhalation. These studies should include both those who use other drugs, such as tobacco, and those not using other drugs. Primary prevention remains the key to stroke prevention, and one should focus on the modifiable risk factors mentioned earlier.4 Future research should be centered on primary prevention and continue to explore possible risk factors,20 as well as on the increasing number of strokes in young adults21 associated with the increased consumption, legalization, and decriminalization of cannabis.5
Until proven otherwise, all patients should be warned about possible dangers of marijuana use in combination with tobacco and other drugs causing an increased risk for stroke.
REFERENCES
- Feigin VL, Krishnamurthi RV, Parmar P, et al. Update on the global burden of ischemic and hemorrhagic stroke in 1990-2013: The GBD 2013 study. Neuroepidemiology 2015;45:161-176.
- Högström G, Nordström A, Eriksson M, Nordström P. Risk factors assessed in adolescence and the later risk of stroke in men: A 33-year follow-up study. Cerebrovasc Dis 2015;39:63-71.
- Wolff V, Armspach JP, Lauer V, et al. Cannabis-related stroke: Myth or reality? Stroke 2013;44:558-563.
- World Health Organization (WHO). The health and social effects of nonmedical cannabis use. Available at: http://www.who.int/substance_abuse/publications/cannabis_report/en/. Accessed March 15, 2017.
- World Drug Report 2015. United Nations Office on Drugs and Crime (UNODC). Available at: http://www.unodc.org/wdr2015/. Accessed March 15, 2017.
- Strong K, Mathers C, Bonita R. Preventing stroke: Saving lives around the world. Lancet Neurol 2007;6:182-187.
- O’Donnell MJ, Xavier D, Liu L, et al; INTERSTROKE Investigators. Risk factors for ischaemic and inter cerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): A case-control study. Lancet 2010;376:112-123.
- Agrawal A, Budney AJ, Lynskey MT. The co-occurring use and misuse of cannabis and tobacco: A review. Addiction 2012;107:1221-1233.
- Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: Evidence from a general population survey. N Z J Public Health 2016;40:226-230.
- Westover AN, McBride S, Haley RW. Stroke in young adults who abuse amphetamines or cocaine; A population-based study of hospitalized patients. Arch Gen Psychiatry 2007;64:495-502.
- Hackam DG. Cannabis and stroke, systematic appraisal of case reports. Stroke 2015;46:1-5.
- Patra J, Taylor B, Irving H, et al. Alcohol consumption and the risk of morbidity and mortality for different stroke types A systematic review and meta-analysis. BMC Public Health 2010;10:258-270.
- Thomas G, Kloner RA, Rezkalla S. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: What cardiologists need to know. Am J Cardiol 2014;113:187-190.
- Rumalla K, Reddy AY, Mittal MK. Recreational marijuana and acute ischemic stroke: A population-based analysis of hospitalized patients in the United States. J Neurol Sci 2016;364:191-196.
- Rumalla K, Reddy AY, Mittal MK. Association of recreational marijuana use with aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis 2015;25:452-460.
- Barber PA, Pridmore HM, Krishnamurthy V, et al. Cannabis, ischemic stroke, and transient ischemic attack: A case-control study. Stroke 2013;44:2327-2329.
- Wolff V, Armspach JP, Lauer V, et al. Ischaemic strokes with reversible vasoconstriction and without thunderclap headache: A variant of the reversible cerebral vasoconstriction syndrome? Cerebrovascular Dis 2015;39:31-38.
- Rabin RA, George TP. A review of co-morbid tobacco and cannabis use disorders: Possible mechanisms to explain high rates of co-use. Am J Addict 2015;24:105-116.
- Esse K, Fossati-Bellani M, Traylor A, Martin-Schild S. Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Brain Behav 2011;1:44-54.
- Peters SA, Huxley RR, Woodward M. Smoking as a risk factor for stroke in women compared with men: A systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke 2013;44:2821-2828.
- Smajlovic D. Strokes in young adults: Epidemiology and prevention. Vasc Health Risk Manag 2015;11:157-164.
No associations between cannabis use in young adulthood and strokes later in life were found in multivariable models. An almost doubled risk of ischemic stroke was observed in those with cannabis use > 50 times; this risk was attenuated when adjusted for tobacco usage. Smoking ≥ 20 cigarettes per day was clearly associated both with strokes before 45 years of age and with strokes throughout the follow-up.
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