Appendix Table 2.

Studies That Examined Exposure to MJ and CVD

Study, Year (Reference) Design	Study Population	Sample Size, n	Age, y	Cannabis Form/Route of Exposure	MJ Exposure Assessment*	Follow-up	Findings†	Risk of Bias	Funding Source
Cardiovascular and all-cause mortality
Yankey et al, 2017 (40) Retrospective	Participants from NHANES	1213	Mean: 37.7 ± 11.2	Plant/smoke	Assessed once at baseline	20 y	MJ users had higher risk for HTN-related mortality (AHR, 3.42 [95% CI, 1.2–9.79]) vs. nonusers but no increase in risk for heart disease mortality (AHR, 1.09 [CI, 0.63–1.88])	High	None
Reis et al, 2017 (35) Prospective cohort	MJ users from CARDIA study	5113	18–30	NS/smoke	Cumulative lifetime exposure was 0.51 MJ-years	26.9 y	≥5 MJ-years (HR, 0.95 [CI, 0.2–4.59]) and recent MJ use (HR, 1.2 [CI, 0.23–6.16]) had no association with CVD mortality In addition, ≥5 years’ MJ use had no association with composite outcome of stroke, CVD mortality, and CAD (AHR, 0.72 [CI, 0.35–1.50])	Moderate	NHLBI, NIA
Frost et al, 2013(39) Prospective cohort	Patients hospitalized with AMI (MIOS)	2097	Mean: 43.7 ± 8.2 (users) and 52 ± 7.7 (nonusers)	NS/NS	Exposure assessed only once. 5.2% of population reported MJ use in the year preceding Ml	18 y	No association between any MJ use and all-cause mortality (HR, 1.29 [CI, 0.81–2.05]; P = 0.28)	High	NIH, Harvard Medical School Scholars in Medicine Office
Mukamal et al, 2008 (38) Prospective cohort	Patients hospitalized with AMI	1913	Mean: 42.6 ± 8.8 (users) and 62.0 ± 12.3 (nonusers)	NS/NS	Users classified as less than weekly and weekly or more. 2.7% of participants reported MJ use in the year preceding Ml	3.8 y	Exposure to any form of MJ was associated with a nonsignificant increased CVD mortality rate (HR, 1.9 [CI, 0.6–6.3]) among patients vs. nonusers MJ use was associated with increased risk for all-cause mortality (HR, 3.0 [CI, 1.3–7.0]; P = 0.009)	High	NHLBI, NlAAA, AHA
AMI
Mittleman et al, 2001 (34) Case-crossover	Patients hospitalized with AMI	3882	Mean: 43.7 ± 8 (users) and 62.0 ± 12.5 (nonusers)	Plant/smoke	Frequency over the past year and most recent use of MJ assessed to estimate exposure within 1 h prior to Ml onset, 3.2% of participants reported MJ use in the year preceding Ml	Median: 4 d	First hour after smoking MJ associated with higher risk for AMI onset (RR, 4.8 [CI, 2.4–9.5];P< 0.001) Association lost in the second hour (RR, 1.7 [CI, 0.6–5.1]; P = 0.34)	Moderate	NHLBI, AHA
Stroke/TIA
Falksted et al, 2017 (36) Prospective cohort	Healthy MJ users	49 321	18–59	NS/NS	Collected once at baseline Exposure status quantified never, 1–10 times, 11–50 times, and >50 times	39 y	Overall, no association between MJ use and stroke (HR, 0.93 [CI, 0.34–2.57]) In addition, MJ use >50 times had no association with ischemic stroke (HR, 1.47 [CI, 0.83–2.56]) after adjustment for tobacco use	High	The Research Council for Health, Working Life and Welfare
Reis et al, 2017 (35) Prospective cohort	Healthy MJ users from CARDIA study	5113	18–30 at baseline	NS/smoke	Cumulative lifetime exposure was 0.51 MJ-years	26.9 y	MJ use had no association with ischemic stroke ATI A (AHR, 0.65 [CI, 0.16–2.66]; P = 0.76) after adjustment for baseline factors	Moderate	NHLBI, NIA
Barber et al, 2013(37) Case-control	Case patients: patients hospitalized for ischemic stroke/TIA	218 case patients and 160 control participants	18–55	Plant/NS	Urine drug screens used to verify exposure	NA	Cannabis use had no association with ischemic stroke/TIA (OR, 1.59 [CI, 0.71–3.70])	High	The Auckland District Health Board A+ Trust provided funding for drug screens
Cerebrovascular mortality
Yankey et al, 2017 (40) Retrospective	Participants from NHANES linked to NCHS	1213	Mean: 37.7 ± 11.2	Plant/smoke	Assessed once at baseline, and one-time users counted as exposed during follow-up	20 y	MJ use was not significantly associated with cerebrovascular mortality (IRR, 1.32 [CI, 0.54–3.43])	High	None
Irregular pulse/arrhythmia
Khiabani et al, 2008 (42) Cross-sectional	Drivers with suspected DUIs	502 case patients and 125 control participants	Mean: 26 (case patients) and 32.5 (control participants)	NS/NS	Exposure status determined from database Frequency, duration, lifetime exposure not measured	NA	THC-positive drivers had a higher mean pulse rate and irregular pulse rate, but no ECGs were recorded to identify the nature of the irregular pulse	High	The Norwegian Institute of Public Health
PVD
Bérard et al, 2013(41) Case-control	Nondiabetic patients with PAD	113 case patient and 241 control participants	Mean: 39 ± 7.8 (case patients) and 33.1 ± 6 (control participants)	NS/smoke	Exposure status determined via questionnaire and urine testing Frequency, duration, lifetime exposure not measured	NA	MJ use had no association with PAD among nondiabetics, but the models were not adjusted for current smoking	High	Fondation de France
MIS
Wolffetal, 2011 (43) Prospective cohort	Patients hospitalized for acute ischemic stroke	48	Mean: 35.5 ± 8	NS/smoke	A questionnaire on drug use was used but no detail given	2 y	Cannabis use had an association with MIS (OR, 113 [CI, 9–5047]; P < 0.001)	High	NS
SAH
Rumalla et al, 2016(44) Cross-sectional	Patients hospitalized for aneurysmal SAH	2104 users and 91 948 nonusers	15–54	NS/NS	Exposure status assessed using ICD-9 codes	NA	Cannabis use was an independent predictor of SAH (OR, 1.18 [CI, 1.12–1.24])	High	NS

AHA = American Heart Association; AHR = adjusted hazard ratio; AMI = acute myocardial infarction; CAD = coronary artery disease; CARDIA = Coronary Artery Risk Development in Young Adults; CVD = cardiovascular disease; DUI = driving under the influence; ECG = electrocardiogram; HR = hazard ratio; HTN = hypertension; ICD-9 = International Classification of Diseases, Ninth Revision; IRR = incidence rate ratio; MI = myocardial infarction; MIOS = Determinants of Myocardial Infarction Onset Study; MIS = multifocal intracranial stenosis; MJ = marijuana; NA = not applicable; NCHS = National Center for Health Statistics; NHANES = National Health and Nutrition Examination Survey; NHLBI = National Heart, Lung, and Blood Institute; NIA = National Institute on Aging; NIAAA = National Institute on Alcohol Abuse and Alcoholism; NIH = National Institutes of Health; NS = not specified; OR = odds ratio; PAD = peripheral arterial disease; PVD = peripheral vascular disease; RR = relative risk; SAH = subarachnoid hemorrhage; THC = Δ9-tetrahydrocannabinol; TIA = transient ischemic attack.

^*Cumulative lifetime exposure listed if presented in study.

^†Reported findings are adjusted for baseline factors unless otherwise indicated.