Waterpipe smoking has developed into a major and rapidly growing global tobacco
epidemic affecting more than 100 million people worldwide. This study identifies
and analyzes comprehensively all available data on the cardiovascular effects of
waterpipe smoking. Databases PubMed, EMBASE, Web of Science, and the Cochrane
Library were searched for studies published until December 2019 assessing
cardiovascular effects of waterpipe smoking. We included experimental, cohort,
cross-sectional and case-control studies and excluded systematic reviews, case
reports/series and qualitative studies. Studies not conducted in humans or not
distinguishing waterpipe smoking from other forms of smoking were also excluded.
A total of 42 studies with 46 cardiovascular parameters were eligible for
analysis. The meta-analysis included 31 studies with 38,037 individuals. Results
showed that one waterpipe smoking session leads to immediate increases in heart
rate and blood pressure (P
Waterpipe smoking (WPS) has developed into a major and rapidly growing global tobacco epidemic worldwide (Maziak et al., 2015). Several factors have hindered recognition of the harmful effects of WPS especially the flavored smoke and the fashionable aspect. In addition, the water gives the impression that it clears most of harmful substances in the smoke. A single WPS session lasts 30-90 minutes of uninterrupted smoking, producing a large volume of smoke which contains up to 80 times more of toxicants than those which found in the smoke of a single cigarette and carried through the water in the bubbles, so the assumption of users that the smoke is ”filtered” by the water is incorrect (El-Zaatari et al., 2015; Shihadeh, 2003). Potential adverse cardiovascular effects of WPS have been reported in several scattered studies with varied results based on different estimation criteria. However, the overall clinical effect of WPS on the cardiovascular system is not clear yet. The few available systematic reviews on this topic were not specifically focused on cardiovascular outcomes or synthesis of the results were not performed, being of limited validity (El-Zaatari et al., 2015; Marshall et al., 2018; Rezk-Hanna and Benowitz, 2019; Waziry et al., 2018). We aimed to explore the clinical cardiovascular effects of WPS quantitatively and qualitatively and to compare them with those of cigarette smoking (CS) by combining all available related data in order to provide a better understanding of the relationship between WPS and cardiovascular disease (CVD) risk.
The analyses were conducted according to a prespecified, non-registered protocol. A systematic literature search was performed for all published original studies on adults with no limitation on the number of participants. The exposure of interest was WPS and the outcomes of interest were any cardiovascular parameters. We included experimental studies assessing the acute effects of WPS and observational studies (i.e. cohort studies, cross-sectional studies and case-control studies) that compared waterpipe smokers to cigarette smokers or non-smokers. Systematic reviews, case reports/case series and qualitative studies were considered not appropriate for inclusion. Furthermore, studies not conducted in humans or not distinguishing WPS from other smoking forms were also excluded (Fig. 1).
PRISMA Flow diagram showing the process of the sytematic search and study selection including eligibility against the inclusion and exclusion criteria. The number of studies is the bottom of the flowchart represents that of the selected studies that were considered eligible for inclusion in this meta-analysis.
Until December 2019, two investigators (R.A., D.V.) independently searched PubMed, EMBASE, Web of Science, and the Cochrane Library using free search text terms combined with Medical Subject Heading (MeSH). The search was performed using variant terms and spellings for waterpipe used in different languages in the title or abstract, or as keywords. Eligibility assessment was performed independently by two investigators (R.A., L.K.). Disagreements were resolved by consulting a third investigator (M.B.).
One investigator extracted the following data from included studies and a second investigator checked the extracted data: 1) study characteristics including study design and settings and sample size; 2) characteristics of study participants including age, gender, health status, smoking status and settings; 3) data concerning outcome measurements for each cardiovascular parameter.
Risk of bias was assessed by two investigators independently (R.A., L.K.) using ROBINS-I (Sterne et al., 2016), a tool recommended from Cochrane Bias Methods Group for assessing the risk of bias in non-randomized interventions. In case of disagreements a third investigator (M.B.) was consulted.
Each analysis was conducted by pooling the appropriate data which could be
extracted from at least three studies that we considered to be sufficiently
similar in their design and comparison groups. Data from experimental studies
were used to assess the acute effects of WPS. Combining data from observational
studies and baseline data from multigroup experimental studies which have similar
control groups were used to assess the non-acute effects of WPS by comparing
waterpipe smokers to non- or cigarette smokers. Using a random-effects model, we
pooled data from each study including sample size with both average value and
standard deviation to estimate pooled mean difference or with prevalence rate to
estimate pooled odds ratio. Results for tested parameters were presented using
Forest plots along with their respective 95% confidence interval (CI). Relevant
statistical heterogeneity was considered as Cochran’s Q test P
After duplicates were removed, the literature search identified 2,141 studies, of which 149 studies investigated WPS effects. We excluded literature reviews, qualitative studies, case reports/series, and studies conducted among teenagers or on animals or machines. Finally, a total of 42 studies were eligible for inclusion in the systematic review. These included 23 observational (case-control and cross-sectional cohort) studies, which compared waterpipe to non- or cigarette smokers, and 19 experimental studies, all of which were non-randomized and investigated the acute effects of WPS, mostly using one-group pretest-posttest design (Fig. 1). One or more potential longitudinal effects of regular WPS were reported in three of these identified studies (Al Suwaidi et al., 2012; Wolfram et al., 2003; Wu et al., 2013).
Forest plots demonstrating individual (squares) and pooled (rhombus) acute changes (mean difference) in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), with corresponding 95% confidence intervals (horizontal lines), obtained after one waterpipe smoking session. WPS: Waterpipe smoking
In all experimental studies each parameter was measured at least twice; at start and end of a 15-90-minute WPS session after 12-72-hour smoking abstinence. In the observational studies, waterpipe smokers were in general those who reported regular WPS, mostly twice a week at least. Time since the last WPS session before measurements was rarely reported. Most the included participants were healthy male adults especially in the experimental and case-control studies, except for 7 studies which conducted on patients with coronary heart disease (CHD) (Table. 1). Generally, the search yielded 46 cardiovascular parameters.
Meta-analysis was conducted on 13 parameters including a total of 31 studies with 38037 participants. Most of this analysis showed a significant heterogeneity, which we considered by pooling the data using a random effects model. Based on ROBINS-I criteria we judged 29 studies with moderate and only 2 studies with serious risk of bias. According to the funnel plots there were no signs of publication bias.
To assess the acute effect of WPS on each of heart rate (HR), systolic blood
pressure (SBP) and diastolic blood pressure (DBP), meta-analysis was conducted
for each of these parameters including 18, 14 and 13 experimental studies with
1814, 1460 and 1386 participants; respectively. Results showed that one WPS
session led to acute increases in mean HR by 10.14 beat/min (95% CI: 8.41 to
Potential WPS effects on cardiac autonomic regulation were investigated in three
experimental studies (Al-Kubati et al., 2006; Cobb et al., 2012; Nelson et al., 2016), revealing markedly impaired HR/BP variation and baroreflex sensitivity
after one WPS session (P
|Study||Study design||Sampling||Participants||N||Male||Age, years Mean
||WPS||CS||NS||Pre-session abstinence||WPS session, min.||Smoking setting||Tobacco used|
|Al-Kubati et al., 2006||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||20||20||27.2
||20||n.s.||n.s.||-||-||12 h||45||Laboratory||5 g moassal|
|Alomari et al., 2014||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||53||34||22.7
||53||n.s.||-||-||n.s.||30||A well-ventilated room||10 g flavoured tobacco|
|Azar et al., 2016||Three-Group Pretest-Posttest||Convenience sampling||Healthy subjects||194||112||35.6 (> 18)||101||n.s.||n.s.||-||42||12 h||15||Restaurants||n.s.|
|Bentur et al.,2014||Two-Group Pretest-Posttest||Convenience sampling||Healthy subjects||62||33||24.9
||47||n.s.||n.s.||-||-||24 h||30||Indoor environment||10 g moassal|
|Blank et al.,2011||One-Group Pretest-Posttest, Two-condition crossover||Convenience sampling||Healthy subjects||37||29||20.5
||37||≤ 5 cig/month||2-5 WP/month||-||-||Overnight||45||Laboratory||10 g flavoured tobacco|
|Cobb et al.,2011||One-Group Pretest-Posttest, Two-condition crossover||Convenience sampling||Healthy subjects||54||36||21.2
||54||54||-||12 h||43.3 (CS 6.1)||Laboratory||n.s.|
|Cobb et al.,2012||One-Group Pretest-Posttest, Two-condition crossover||Convenience sampling||Healthy subjects||32||16||21.6
||32||≤ 5 cig/month||32||-||12 h||45||Laboratory||10 g flavoured tobacco|
|Eissenberg and Shihadeh,2009||One-Group Pretest-Posttest, Two-condition crossover||Voluntary response sampling||Healthy subjects||31||21||21.4
||31||31||-||45 (CS 5)||Laboratory||15 g flavoured tobacco|
|Elias et al.,2012||Two-Group Pretest-Posttest||Convenience sampling||Healthy subjects||100||n.s.||29.5
||70||70||weekly WPS, (6.9
|Hakim et al.,2011||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||45||30||32.3
||45||37||Regularly||-||-||24 h||30||An outdoor environment.||10 g moassal|
|Hawari et al.,2013||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||24||24||20.4 (18-25)||24||n.s.||4 (0.5-14) WP/week||-||-||45||Laboratory||n.s.|
|Kadhum et al.,2014||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||61||49||(18-25)||61||61||n.s.||-||-||45-90||Cafes||n.s.|
|Layoun et al.,2014||Three-Group Pretest-Posttest||Convenience sampling||n.s.||132||87||33.4 (
||42||42||48||42||n.s.||45||Restaurants||20 g moassal|
|Nelson et al.,2016||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||28||20||27
||28||28||¿ 12 times in the past year||-||-||72 h||30 (102
|Rezk-Hanna et al.,2019||Two-Group Pretest-Posttest||Voluntary response sampling||Healthy subjects||55||10||26
|Shafagoj and Mohammed,2002||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||18||18||27
||18||18||-||-||84 h||45||Laboratory||20 g moassal|
|Shaikh et al.,2008||One-Group Pretest-Posttest||Cluster sampling||Healthy subjects||202||202||33.2 (¿ 17)||202||202||n.s.||-||-||20 min||30-45||Café||n.s.|
|Shishani et al.,2014||One-Group Pretest-Posttest Two-condition crossover||Voluntary response sampling||Healthy subjects||22||n.s.||23
||22||22||-||-||24 h||45–60||Outdoor laboratory||n.s.|
|Wolfram et al.,2003||One-Group Pretest-Posttest||Convenience sampling||Healthy subjects||7||7||7||7||occasionally||-||-||3 months||55 (45-70)||Laboratory||15 g of tobacco|
|Al-Amri et al.,2019||Case-control hospital-based||Convenience sampling||Cases are myocardial infarction, controls from dermatology and surgery departments||296||203||47.8
|Al-Numair et al.,2007||Case-control||Convenience sampling||Healthy subjects||200||200||(19-50)||100||100||Daily||-||100||n.s.||-||-||ma’ssel|
|Chami et al.,2019||Case-control community-based||Convenience and voluntary response sampling||Healthy subjects||345||233||53.7
|Chwyeed,2018||Case-control||Randomly selection||Healthy subjects||75||75||(30-60)||20||20||n.s.||20||35||n.s.||-||-||n.s.|
|Diab et al.,2015||Case-control||Convenience sampling||Healthy subjects||77||77||35.1
|Ghasemi et al.,2010||Case-control community-based||Convenience sampling||Healthy subjects||54||54||33.3
||27||27||Daily||-||27||n.s.||-||-||mostly of moassal|
|Hashem Sezavar et al.,2004||Case-control community-based||Convenience sampling||n.s.||450||450||(20-75)||150||150||Daily||150||150||n.s.||-||-||n.s.|
|Jabbour et al.,2003||Case-control hospital-based||Convenience sampling||Cases are CHD patients, controls recruited from 3 hospitals||525||n.s.||n.s.||49||n.s.||¿ 4/week||-||299||n.s.||-||-||n.s.|
|Koubaa et al.,2015a||Case-control community-based||Convenience sampling||Healthy subjects||43||43||43.6
||14||14||15||14||n.s.||-||-||10 and 25 g|
|Koubaa et al.,2015b||Case-control community-based||Convenience sampling||Healthy subjects||43||43||43.6
||14||14||15||14||n.s.||-||-||10 and 25 g|
|Muddathir et al.,2018||Case-control||Convenience sampling||Healthy subjects||120||80||29.2 (18-51)||40||40||Daily||40||40||n.s.||-||-||n.s.|
|Selim et al.,2013a||Case-control community-based||Convenience sampling||Healthy subjects||70||63||28.7 (25-35)||30||30||Daily||30||10||n.s.||-||-||n.s.|
|Al Suwaidi et al.,2012||Cross-sectional prospective hospital-based cohort||Convenience sampling||ACS patients||7930||6253||59.6||130||130||Regular||3605||3742||-||-||-||n.s.|
|Al-Safi et al.,2009||Cross-sectional population-based||Stratified cluster random sampling||Healthy subjects||14310||7400||31.4 (
|Islami et al.,2013||Cross-sectional prospective population-based cohort||Systematic clustering random sampling||Cases: participants with heart disease history, Controls: participants with no heart disease history||50045||21234||(40-75)||525||n.s.||Ever||-||49489||n.s.||-||-||n.s.|
|Khan et al.,2020||Cross-sectional community-based||Voluntary response sampling||Healthy subjects||73||41||39.8 (21-65)||12||12||Daily||26||25||n.s.||-||-||n.s.|
|Platt et al.,2017||Cross-sectional hospital-based||Convenience sampling||Coronary angiography patients||7705||5188||61.2
|Saffar Soflaei et al.,2018||Cross-sectional population-based||Stratified cluster random sampling||-||9690||n.s.||(35-65)||1067||1067||n.s.||864||6742||n.s.||-||-||n.s.|
|Selim et al.,2013b||Cross-sectional hospital-based||Convenience sampling||Coronary angiography patients||287||n.s.||n.s.||63||63||Regularly||100||109||n.s.||-||-||n.s.|
|Shafique et al.,2012||Cross-sectional population-based cohort||Voluntary response sampling||Healthy subjects||2032||1039||(30-75)||325||325||-||1707||n.s.||-||-||n.s.|
|Sibai et al.,2014||Cross-sectional hospital-based||Convenience sampling||Coronary angiography patients||1754||n.s.||(
|Ward et al.,2015||Cross-sectional population-based||Stratified cluster random sampling||-||2536||1220||25-65||286||n.s.||Regularly||-||2134||n.s.||-||-||n.s.|
|Wu et al.,2013||Cross-sectional prospective population-based cohort||Convenience sampling||n.s.||20033||1971||(18-75)||n.s.||n.s.||Ever regularly||n.s.||n.s.||n.s.||-||-||n.s.|
|WP: Waterpipe, WPS: Waterpipe smoking, CS: Cigarette smoking, ACS: Acute coronary syndrome. CHD: Coronary heart disease. n.s.: Not specified.|
Immediate effects of WPS on endothelial function was investigated through
oxidative stress in one study evaluated the acute effect of WPS on the oxidative
status (Wolfram et al., 2003), showing a significant increase in mean
malondialdehyde from 3.6
To investigate the potential acute effect of WPS on vascular function, different
clinical methods were used in three experimental (Alomari et al., 2014; Bentur et al., 2014; Rezk-Hanna et al., 2019) and two case-control (Diab et al., 2015; Selim et al., 2013a) studies. One WPS session led to a significantly
acute reduction in arterial blood flow by -8.8% (P = 0.035) and
increase in arterial vascular resistance by 16% (P = 0.003) using
strain-gauge plethysmography (Alomari et al., 2014), while no acute changes
were observed in arterial pulse wave amplitude using ”EndoPat” device (Bentur et al., 2014). However, an acute reduction in flow-mediated dilatation (FMD) by
28% was observed after one WPS session (P
Meta-analysis was conducted using data from 10 studies with 14909 participants
for HR, 12 studies with 17386 participants for SBP and DBP and 5 studies with
5742 participants for having hypertension. Results showed an increased mean HR by
2.12 (95% CI: 0.11 to 4.13; P = 0.04) with a tendency to have higher
blood pressure (BP) among waterpipe smokers compared to non-smokers (Fig. 3).
No significant association between WPS and any of these hemodynamic parameters
was observed in meta-analysis after eliminating the statistical heterogeneity in
sensitivity analyses. However, a large population-based cross-sectional study
with 14310 participants (Al-Safi et al., 2009) showed a significant
correlation between hemodynamic status and frequency of WPS. Compared to
non-smokers, waterpipe smokers of 1-2 sessions/week had higher mean HR by
Forest plots demonstrating individual (squares) and pooled (rhombus) mean differences in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), with corresponding 95% confidence intervals (horizontal lines), obtained in waterpipe smokers compared to non-smokers. WPS: Waterpipe smoking. NS: Non-smoking.
The potential correlation of WPS with serum lipid levels was investigated by
conducting the meta-analysis for each of total cholesterol, low-density
lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol,
triglyceride and having dyslipidemia including 5, 6, 7, 6, and 5 observational
studies with 12120, 12320, 14352, 14007 and 13206 participants; respectively.
Results demonstrated increased mean LDL-cholesterol by 8.77 mg/dl (95% CI: 0.55
to 17.0; P = 0.04) and triglyceride by 30.6 mg/dl (95% CI: 14.4 to
Forest plots demonstrating individual (squares) and pooled (rhombus) mean differences in blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglyceride (TG), with corresponding 95% confidence intervals (horizontal lines), obtained in waterpipe smokers compared to non-smokers. WPS: Waterpipe smoking. NS: Non-smoking.
One case-control study (Al-Numair et al., 2007) compared apolipoproteins
(Apo) between waterpipe smokers and non-smokers, revealing decreased mean Apo-A1
Three case-control studies investigated the association between WPS and
fibrinogen (Hashem Sezavar et al., 2004; Khan et al., 2020; Muddathir et al., 2018), where significantly increased levels of fibrinogen by about 15-25% were
observed among waterpipe smokers compared to non-smokers (P
Factor-VII and VIII were investigated in one study (Muddathir et al., 2018),
showing higher levels by about 25% and 50%, respectively, in waterpipe smokers
than in non-smokers, especially in those who smoked waterpipe for more than 3
No significant long-term effect has been reported on Serpine1/Plasminogen activator inhibitor-1 (Khan et al., 2020).
One study investigated the longitudinal effect of WPS on the oxidative status (Wolfram et al., 2003). Blood levels of malondialdehyde, 11-DH-TXB2 and 8-epi-PGF2a continued to rise over two weeks of daily WPS and remained significantly elevated even before the initiation of a new WPS session.
Two (Al-Numair et al., 2007; Koubaa et al., 2015a) of three studies
(Al-Numair et al., 2007; Khan et al., 2020; Koubaa et al., 2015a) observed
significantly increased levels of malondialdehyde among waterpipe smokers
compared to non-smokers. These two studies also showed significantly reduced
levels of total antioxidant capacity (TAC) among waterpipe smokers compared to
In one study, Nitric oxide (NO) metabolites were measured in waterpipe smokers
(Ghasemi et al., 2010) demonstrating higher levels than in non-smokers (34.3
vs. 22.5 micromol/l; P
Two case-control studies evaluated the potential non-acute effect of regular WPS
on FMD, where lower FMD values by about 30-60% were observed in waterpipe
smokers than in non-smokers (P
Our meta-analysis showed that waterpipe smokers had a higher mean fasting blood
glucose (FBG) of 4.66 mg/dl (95% CI: 0.53 to 8.80; P = 0.03) than
non-smokers did, with no association between WPS and having diabetes mellitus
(DM). After removing the statistical heterogeneity in sensitivity analyses, a
significant correlation was revealed between WPS and both of DM (OR = 1.35; 95%
CI: 1.16 to 1.57; P
No difference was observed between waterpipe smokers and non-smokers regarding
body mass index (BMI) in our meta-analysis. However, two population-based
cross-sectional studies observed a significant association between obesity and
each of regular waterpipe smokers (OR = 1.44; 95% CI: 1.26 to 1.65; P
Two population-based studies (Saffar Soflaei et al., 2018; Shafique et al., 2012) assessed the potential correlation of WPS with metabolic syndrome (MS).
Waterpipe smokers were more likely to have MS compared to non-smokers (OR = 1.29;
95% CI: 1.12 to 1.48; P
One case-control study (Chami et al., 2019) evaluated the 10-year CHD risk
in waterpipe smokers, showing higher mean risk score in waterpipe smokers than in
Coronary Artery Calcium (CAC) score was measured among waterpipe smokers in one
case-control study (Chami et al., 2019). Waterpipe smokers had higher mean
CAC score than non-smokers did (90.6
A significant correlation between WPS and the incidence of CVD was reported in
four out of seven differently designed studies (Al Suwaidi et al., 2012; Al-Amri et al., 2019; Chami et al., 2019; Islami et al., 2013; Jabbour et al., 2003; Platt et al., 2017; Saffar Soflaei et al., 2018). In a large
population-based cohort study with 50045 participants (Islami et al., 2013)
heart disease correlated to the consumption of
Two cross-sectional studies assessed the correlation between WPS and the
severity of coronary artery disease (CAD). Compared to non-smokers, waterpipe
smokers had a higher mean Duke Jeopardy score (DJS) of anatomical extension of
The relationship between WPS and CVD outcomes was investigated in two
cross-sectional studies (Al Suwaidi et al., 2012; Wu et al., 2013). Among
patients with ACS, waterpipe smokers were more likely to develop arrhythmias at
presentation (OR = 2.0; 95% CI: 1.08 to 3.69; P = 0.026) and
in-hospital complications (OR = 2.7; CI 95%: 1.85 to 3.88, P
Meta-analysis including data from seven observational studies with 7842
participants showed no differences between waterpipe and cigarette smokers
regarding HR, SBP or DBP (Fig. 5). After removing the statistical
heterogeneity in sensitivity analyses, significantly increased mean HR by 3.21
(95% CI: 2.31 to 4.11; P
Forest plots demonstrating individual (squares) and pooled (rhombus) mean differences in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), with corresponding 95% confidence intervals (horizontal lines), obtained in waterpipe smokers compared to cigarette smokers. WPS: Waterpipe smoking. CS: Cigarette smoking.
Pooled data from three observational studies with 5721 participants showed
higher mean total cholesterol of 6.80 mg/dl (95% CI: 3.23 to 10.38; P
Forest plots demonstrating individual (squares) and pooled (rhombus) mean differences in blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglyceride (TG), with corresponding 95% confidence intervals (horizontal lines), obtained in waterpipe smokers compared to cigarette smokers. WPS: Waterpipe smoking. CS: Cigarette smoking.
Meta-analysis showed no differences regarding mean BMI and prevalence of DM
between waterpipe and cigarette smokers. However, one of two studies (Saffar Soflaei et al., 2018; Selim et al., 2013b) reprted a higher obesity rat (OR =
4.19; 95% CI: 3.33 to 5.28; P
Meta-analysis showed no difference regarding FMD between waterpipe and cigarette smokers. Furthermore, the three studies that compared CRP levels (Diab et al., 2015; Khan et al., 2020; Saffar Soflaei et al., 2018) and the two studies that compared levels of malondialdehyde and TAC (Khan et al., 2020; Koubaa et al., 2015a) observed no differences between waterpipe and cigarette smokers.
In two of the three case-control studies (Hashem Sezavar et al., 2004; Khan et al., 2020; Muddathir et al., 2018), waterpipe smokers had significantly higher
levels of fibrinogen than cigarette smokers did (P
Different aspects of CVD were compared between waterpipe and cigarette smokers
in three studies (Al Suwaidi et al., 2012; Saffar Soflaei et al., 2018; Selim et al., 2013b). No differences were observed regarding CVD incidence (Al Suwaidi et al., 2012; Saffar Soflaei et al., 2018). However, higher mean DJS
was also observed in waterpipe than in cigarette smokers in a cross-sectional
study conducted on CAD patients (P
The main findings of our analyses are: i) WPS leads to an acute increase in HR, SBP and DBP; ii) waterpipe smokers have increased HR, higher triglyceride and LDL-Cholesterol and lower HDL-Cholesterol levels compared to non-smokers; iii) the cardiometabolic profile in waterpipe smokers is not less worse than in cigarette smokers.
It is well known that increased HR and BP, the two most widely used hemodynamic parameters in assessment of cardiovascular system, negatively affect cardiovascular outcome. (Ettehad et al., 2016; Nikolovska Vukadinović et al., 2017). According to our results one WPS session causes acute increase in HR by about 11 beats/minute, SBP by 7 mmHg und DBP by 5 mmHg. This itself may lead to increased oxygen demand of the heart, augment shear stress of the blood vessel, which in some cases may provoke ACS, thereby increasing morbidity and mortality. Based on available data, it is not known how long these acute hemodynamic effects of WPS might last. The answer to this question needs more studies with serial measurements of these parameters. As waterpipe is mostly consumed regularly for several times a week, it could be expected that accumulation of these acute adverse effects negatively impacts prognosis over time. However, our results show that waterpipe smokers had slightly increased HR in comparison with non-smokers for about 2 beats/minute, while SBD and DBP tend to be higher among waterpipe smokers but without reaching the statistical significance. These results differ somewhat unexpectedly from those observed with the acute effects of WPS, which could be partially explained through large heterogeneity across the studies. Furthermore, frequency and duration of WPS sessions and years of smoking were not adjusted across the studies, which might affect the results. A significant positive correlation was previously observed between the number of weekly use of waterpipe and each of SBP, SBP and HR (Al-Safi et al., 2009). The acute hemodynamic changes revealed in our analyses may be attributed to some extent to nicotine exposure, which augments the sympathetic nervous system activity, leading to increases in HR, myocardial contractility and cardiac output (Salahuddin et al., 2012). Such an effect has been reported in the three cross-over design studies (Blank et al., 2011; Cobb et al., 2012; Shishani et al., 2014) comparing flavor-matched tobacco- with tobacco-free-WPS. However, an acute cardiac autonomic dysregulation was observed after a WPS session independently of nicotine content (Cobb et al., 2012). In addition, the high levels of exposed CO during WPS (Eissenberg and Shihadeh, 2009) can lead to decreased oxygen supply to tissues including the heart due to the formation of CO-Hb (Benowitz, 2003). In turn, it has been well established that hypoxia is a potent stimulator of several autonomic mechanisms leading to increases in resting HR, BP and cardiac output (Vigo et al., 2010). These findings contradict harm reduction claims of so-called “herbal” waterpipe-products and correspond to outcomes of non-clinical studies on such products using a human-mimic waterpipe-machine (Hammal et al., 2015). Owing to the lack of data from longitudinal studies, it is not possible to determine to what extent WPS can be hemodynamically harmful at the long-term.
Pooling data from available studies revealed a significant correlation between WPS and increased triglyceride and LDL-cholesterol and decreased HDL-cholesterol, which are recognized as CVD risk factors that promote atherosclerosis (Pedro-Botet et al., 2020). As is well known for CS, the mechanisms responsible are not clearly elucidated. However, the triglyceride/high-density lipoprotein abnormalities have recently been suggested to be related to insulin resistance. (Ambrose and Barua, 2004). This can be supported with our results that showed a significant increase in FBG in waterpipe smokers compared to non-smokers.
The association between CS and increased activity of coagulation factors and thrombotic risk has been previously reported (Eliasson, 1995). Likewise, WPS also correlates with increased levels of fibrinogen and factors VII and VIII (Hashem Sezavar et al., 2004; Khan et al., 2020; Muddathir et al., 2018), which may increase thrombogenicity, thus increasing the risk for cardiovascular events. The harmful effects of WPS are reflected by the increased CAC score (Chami et al., 2019) and the acute (Alomari et al., 2014; Rezk-Hanna et al., 2019; Wolfram et al., 2003) and long-term (Al-Numair et al., 2007; Diab et al., 2015; Ghasemi et al., 2010; Koubaa et al., 2015a; Selim et al., 2013a) endothelial dysfunction, which were established among waterpipe smokers, providing clinical evidence for the potential contribution of WPS to vascular disease. Our findings on WPS effects on cardiovascular system explain and support results of studies which reported a significant correlation between WPS and each of incidence (Al-Amri et al., 2019; Islami et al., 2013; Jabbour et al., 2003; Platt et al., 2017), worse clinical outcomes (Al Suwaidi et al., 2012) and estimated prognoses (Selim et al., 2013b; Sibai et al., 2014) of CVD.
As cardiovascular effects of CS are well known (Ambrose and Barua, 2004; Leone, 2003; Mons et al., 2015), the comparison between WPS and CS is of a great importance. Unfortunately, fewer studies could be included for this comparison. The lack of studies reporting the rate of cardiovascular and cerebrovascular events in waterpipe vs cigarette smokers may be the main limitation. However, based on our results, the non-acute effects of WPS on the vast majority of cardiovascular parameters of interest seem similar to those produced by CS. The few available studies showed no clear difference in the CVD incidence between WPS and CS (Al Suwaidi et al., 2012; Saffar Soflaei et al., 2018). Furhtermore, CVD complications (Al Suwaidi et al., 2012) and mortality (Al Suwaidi et al., 2012) tend to be of higher rates in waterpipe than in cigarette smokers. This might be explained due to prolonged WPS and, therefore, cumulatively higher amounts of inhaled toxic substances and consequently adverse effects on the cardiovascular system (Sibai et al., 2014).
A limitation of these analyses is the high heterogeneity of the available data. This can be attributed to the geographic diversity of the analyzed studies, the multiple study protocols, as well as different frequency and session duration of WPS. Furthermore, some parameters were reported in only few studies, which limits the explanatory power of this analysis. Therefore, some results should be interpreted with caution. As long-term follow-up studies on cardiovascular effects of WPS are scarce, chronic effect of WPS has been estimated in our analyses using data from available case-control and cross-sectional cohort studies that compared waterpipe smokers to non-smokers. Of note, the observed effects could be explained solely due to WPS, as limited number of waterpipe smokers may occasionally have also smoked cigarettes. Although the comparison between WPS and CS may be the most important part of systematic review, only few studies are available for this comparison, with the main limitation is the lack of studies reporting the rate of cardiovascular and cerebrovascular events. On the other hand, some waterpipe smokers could be ex-cigarette smokers. The time spent smoking cigarette are likely impacting, observed outcomes. Such information is missed in most observational studies. Thus, a meta-regression considering time from quitting of cigarette smoking in waterpipe smokers is not possible. This applies to the other results showed a worst cardiometabolic profile of waterpipe smokers compared to non-smokers, as many studies did not consider all potential confounders in the comparisons. To the best of our knowledge, our study provides the most comprehensive image of the potential cardiovascular effects of WPS based on scientific evidence and reflects the current magnitude of research efforts performed so far regarding this issue.
There is still a widespread believe that WPS is harmless and not real smoking. This wide-ranged systematic review and meta-analysis outlines the spectrum of acute and long-term cardiovascular effects of waterpipe smoking. Despite all the stated limitations, current level of evidence suggests that WPS is associated with substantial adverse effects on cardiovascular system, which seem to be similar to what reported for cigarette smoking. Further research is required especially longitudinal studies evaluating the long-term consequences of both waterpipe smoking and cessation to scrutinize the magnitude of these effects and to provide a strong evidence for a causal relationship.
Concept and design: RA and MB. Literature search for eligible studies: RA, DV, and LK. Data extraction and quality assessment: RA and LK. Data analysis and interpretation: RA, MB and DV. Writing of original draft: RA. Review and editing of article: all authors. Critical revision of article: RA, MB and DV. Approval of article: all authors.
The authors thank all the peer reviewers and editors for their opinions and suggestions.
Authors do not have any conflict of interest related to this study.