Table 1.

Characteristics of systematic reviews on the cardiovascular health risks of e-cigarettes.

Author, Year	Funding/COI Disclosures of Review Authors	Review Objectives	Date Range of Literature Search	Evidence Type	Health Outcome Measures		Study Designs	Population	Number of Included Studies	Exposure	Vaping Devices
					Acute	Chronic
Garcia et al., 2020 [30]	The authors declare no conflict of interest. The work was supported by the Tobacco-Related Disease Research Program (TRDRP)	Synthesize studies that have investigated the autonomic CV effects of ECs in humans: (1) Acute effects of ECs vs. TCs. (2) Comparison of acute effects by nicotine vs. non-nicotine containing ECs. (3) Chronic Effects of ECs (in non-TC smokers). (4) Relative chronic effects of ECs compared to TCs (switching).	Through December 2019	Human	Acute (minutes to hours after EC use) changes in heart rate variability (HRV), heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP).	Chronic * (days or longer) changes in HRV, HR, SBP, and DBP	Experimental (control trials)	Aim 1: TC smokers. Aim 2: TC smokers and nicotine-naive participants. Aim 3: chronic EC users (no TC or dual use). Aim 4: chronic TC smokers.	19 in total. Eight on acute effects of TC versus EC (with or without nicotine). Five on acute effects of EC with vs. without nicotine. Two on chronic effects of EC. Six on switching from chronic TC to chronic EC use.	Acute and chronic EC use (with or without nicotine).	Earlier generation EC devices
Skotsimara et al., 2019 § [22]	The authors declare no conflict of interest.	Meta-analysis and systematic review of studies that have investigated: 1. Acute effects of ECs. 2. Effects of switching from TC use to chronic EC use on a CV system.	January 2000–November 2017	Human, in vitro	Acute (5–30 min after EC use) changes in HR, SBP, and DBP	Chronic * (assessment time range 5 days–1 year) changes in HR, SBP, and DBP. Secondary outcomes: Arterial stiffness, endothelial function, myocardial function, and risk of cardiovascular events.	Experimental (randomized and non-randomized control trials) for meta-analysis. Experimental bench studies and clinical trials for Systematic Review.	Studies included healthy smokers (10), hypertensive smokers (1), healthy non-smokers (1) and EC users (or dual users) (2).	26 studies included in a systematic review, 14 studies in the meta-analysis. Of 14, 11 studied acute effects (of them 11 on HR and 7 on BP); three studied chronic effects.	Acute and chronic EC use. Duration of exposure in in vitro studies not reported.	In meta-analysis, a classic tobacco EC in rechargeable cartomizer 2.4% nicotine, 75% glycerin vehicle was the commonest type used across studies. When different nicotine EC types were used, the higher nicotine type was included. Where relevant, only non-flavored EC type was used.
Kennedy et al., 2019 [15]	N/A	Summarize of physiological and pathophysiological cardiovascular effects after direct exposure to EC.	1996 to June 2019	Human, Animal, in vitro	Sympathetic nerve activation (HR, HRV, SBP, and DBP), oxidative stress, endothelial function, and platelet activation.	N/A	Experimental (randomized control trials, non-randomized control trials, randomized crossover studies, and non-randomized crossover studies).	Adults with or without cardiovascular disease, independent of smoking status or age.	38 studies total. Of them, 24 human studies (18 measured HR, 17 measured BP); six animal studies, and eight cardiovascular cell culture studies.	Direct EC use (human studies), Inhalation of EC vapor (animal studies); Cellular exposure to EC vapor (range 4 to 72 h).	Devices varied across studies, predominantly first and second generation EC devices.
Glasser et al., 2017 [28]	N/A	Synthesize empirical studies on electronic nicotine delivery systems across a broad range of topics, including the health effects.	Through 31 May 2016	Human, in vitro	Physiologic health effects, such as HR and blood pressure (time of assessment unspecified). Anti-inflammatory process, oxidative stress, and changes in cell apoptosis.		Experimental, quasi-experimental, observational (case control, cohort, and cross-sectional studies), case reports, case series, qualitative studies, mixed methods, and in vitro.	N/A	129: 116 articles on the impact of vaping on human health and 13 on animal health.	Exposure to vapor (duration not specified).	N/A
Pisinger & Dossing, 2014 [21]	The authors declare no conflict of interest.	(1) Systematic and critical review of the existing literature on the health consequences of ECs and discuss the implications of our findings for public health; (2) to investigate how many of the published articles have a conflict of interest.	Through 24 August 2014	Human	HR, blood pressure, oxygen saturation, and cardiac function.	N/A	Experimental	Not specified.	Eight studies on cardiovascular health effects.	Short-term EC use (minutes).	N/A
Bozier et al., 2020 [18]	The authors declare no conflict of interest.	(1) To provide a comprehensive update of data on the potential health effects of ECs since the NASEM report. (2) To provide a focused discussion of the scientific literature that will help inform the general public, health-care practitioners, and policy makers of the effects of EC use on health.	February 2017 through May 2019	Human, Animal	HR, HRV, blood pressure, and arterial stiffness (time of assessment unspecified).		Experimental, observational, and case reports.	Not specified.	Eight studies on cardiovascular health effects.	EC use and exposure to EC vapor (no data on the duration).	N/A
Harrell et al., 2014 [19]	The authors declare no conflict of interest. One co-author reports to be receiving research support from a pharmaceutical company, a manufacturer of a stop smoking medication.	To have a summary of the current, relevant literature on EC safety and efficacy.	Through November 2013	Human	Acute changes in HR, inflammatory markers, myocardial function, and arrhythmia (no definition of “acute”).	N/A	Case series and case reports.	Not specified. The results show that some studies included smokers and never smokers. No information on their health.	Eight studies on acute physiological effects.	EC use (no data on the duration).	EC devices reported partially in a Table with study characteristics. No summary or discussion provided.
Ioakeimidis et al., 2016 [20]	N/A	To highlight the efficacy for smoking cessation and the potential hazards of EC use.	Through June 2015	Human	Acute and long-term cardiovascular outcomes (SBP, DPB, arrhythmia, aortic stiffness, and myocardial relaxation) (No definition of “acute” or “long-term”).		Not specified. Original studies as well as review articles and statements are included.	N/A	20 original studies and eight review articles and statements.	EC use (no data on the duration).	N/A
NASEM, 2018 [16]	N/A	To evaluate the available evidence of the health effects related to the use of electronic nicotine delivery systems (ENDS) and identify future federally funded research needs.	1 February 2017–31 August 2017	Human	Acute CV outcomes: HR, SBP, DBP, oxidative stress, endothelial function, arterial stiffness, and cardiac geometry and function.	Long-term CV outcomes: clinical (coronary heart disease, stroke, and peripheral artery disease) and subclinical atherosclerosis (carotid intima-media thickness, and coronary artery calcification).	Experimental, observational	In acute effects studies: a range of 23 to 39 y.o. In longer-term effect studies: a range of 33 to 54 y.o Generally healthy participants, one study included participants with hypertension.	13 studies on acute and three studies on longer-term cardiovascular effects.	Acute (minutes to hours) and long-term (not further defined) vaping.	A tank-style device in one study; second-generation devices in three studies; cigalikes in six studies; one leading brand of an unspecified device in one study; and the personal devices of the study participants in two studies.
Goniewicz et al., 2020 [24]	First author received research grant from Pfizer and personal fees from Johnson & Johnson outside of this work. The other authors had nothing to declare.	To conduct a systematic review of epidemiological studies that estimated the odds of key cardiovascular outcomes among EC users who formerly smoked, compared with current smokers who do not use ECs.	Through September 2020	Human	Cardiovascular outcomes (e.g., stroke, myocardial infarction, coronary heart disease).		Observational	Adult former smokers who transitioned to EC use and current exclusive TC smokers (as a comparator).	Three cross-sectional studies.	EC use (no data on the duration).	N/A
Larue et al., 2021 § [29]	No competing interests for this work were declared. The review protocol declares that a family member of the lead author works in tobacco industry.	To assess the immediate cardiovascular effects of acute EC use.	Through 20 May 2021	Human	SBP, DBP, HR	N/A	Experimental	Mostly healthy participants. Current smokers and non-smokers.	22 cross-over and randomized trial studies.	Duration of EC use (with and without nicotine) ranged from 3 to 30 min. Assessment time occurred between 1 and 30 min post use.	Different brands of ECs with varying nicotine content.
Martinez-Morata et al., 2020 [26]	The authors declare no conflict of interest.	To summarize the available studies on the short-term effects of ECs on blood pressure in experimental studies, and the association between ECs and blood pressure endpoints in observational studies.	2003 through April 2020	Human	SBP, DBP	N/A	Experimental, observational	Healthy adult participants with no prior diagnosis of hypertension.	13 randomized trials and one prospective study.	EC use with outcome assessment up to 4 h post use.	Information was collected and presented in a tabular format. No stratified analysis by device type or discussion of the impact of device type on the outcome was provided.

§ Meta-analysis. COI = conflict of interest; EC = electronic cigarettes; TC = traditional cigarettes; SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate; HRV = heart rate variation; and N/A = not available. * Chronic effects were described as those measured in chronic EC users (non-TC smokers) and in TC smokers after switching to chronic EC.