Water pipe smoking and stroke: A systematic review and meta‐analysis

Abstract Objective Despite the damaging effects of water pipe on physical health, there is little information about the potential harmful effects of this tobacco on stroke. This study aims to investigate the relationship between water pipe smoking and stroke. Method A systematic review was conducted including Ovid SP, Embase, Pubmed, Web of Science, Scopus, and Google Scholar databases with focus on cohort, case–control, and cross‐sectional studies. We reviewed all studies reporting on water pipe smoking and stroke. The funnel plot and the Egger regression test were used to assess publication bias. Results In the four eligible studies, there were a total of 2759 participants that 555 patients had at least once experienced stroke. Meta‐analysis revealed positive association between water pipe smoking and stroke with pooled adjusted OR 2.79 (95% CI: 1.74–3.84; I2=0,p=.741) and the funnel plot shows asymmetry publication bias. Conclusions We found a higher effect of water pipe smoking on stroke compared to cigarette smoking and concluded that water pipe increases the risk of stroke by 2.79. Hence, because most of the water pipe consumer society is young, especially women, policies and decisions need to be taken to control the supply of this tobacco to the market and more provide education on the health problem of water pipe smoking. Implications This study provides a higher effect of water pipe smoking on stroke. Physicians and researchers who intend to study in the field of stroke should better examine the effects of water pipe (including time of use, dose–response, long‐term effects, and risk factors) on stroke.


INTRODUCTION
Stroke, the second leading cause of mortality worldwide, exerts a profound impact on global public health, contributing significantly to both premature death and the burden of disability-adjusted life years (Zhang et al., 2019).In developed countries, the annual death toll from stroke ranges from 50 to 100 per 100,000 individuals (Donnan et al., 2008).This multifaceted health crisis is influenced by a constellation of risk factors, which encompass tobacco smoking, high blood pressure, obesity, high blood cholesterol, hyperlipidemia, coronary heart disease, heavy episodic alcohol consumption, low physical activity, and diabetes (Aigner et al., 2017;Donnan et al., 2008;Zhang et al., 2019).
Among these risk factors, tobacco usage stands as a prominent global contributor to premature mortality (Jassem, 2019).
One particular method of tobacco consumption that has gained popularity worldwide is the water pipe, known by various names as hookah, hubble-bubble, narghile, shisha, and qalyan (in Persian) (Montazeri et al., 2017).Its origins trace back approximately 500 years to the regions of Persia (present-day Iran), Pakistan, and India, from where it gradually diffused across the Middle Eastern (Blachman-Braun et al., 2014;Montazeri et al., 2017).In recent years, there has been a substantial surge in water pipe use among youth in European, American, African, and Asian (Blachman-Braun et al., 2014;Momenabadi et al., 2016).Alarmingly, a report from the World Health Organization reveals that the average water pipe smoking session lasts between 20 and 80 min, which is equivalent to or even surpasses the nicotine intake of smoking more than 100 cigarettes a day (Blachman-Braun et al., 2014;Kim et al., 2016).Remarkably, the volume of smoke generated by water pipe usage is greater that of traditional cigarettes by a factor of 4400-4500 units (Momenabadi et al., 2016).
This context underscores the magnitude of the issue at hand and the need for a comprehensive examination.Notably, the concentration of nicotine in the bloodstream of a daily cigarette smoker is just a fraction of that found in a daily water pipe user (0.1 times) (Kim et al., 2016).
Therefore, this study endeavors to present a meta-analysis of observational studies that delves into the relationship between water pipe smoking and the risk of stroke, an area of research that, though limited, merits attention

METHODS
We performed the current systematic review and meta-analysis according to the PRISMA checklist (Moher et al., 2015).

Search strategy
The present study was conducted using the six databases (PubMed,

Inclusion and exclusion criteria
Studies should meet (1) the observational study (cohort, case-control, and cross-sectional), ( 2) study provided the relationship between water pipe and stroke, and (3) reported the odds ratio (OR) and 95% confidence interval (CI) of relationship between water pipe and stroke, criteria to enter the study.
Exclusion criteria included (1) the stroke patients without a history of water pipe smoking, (2) did not report OR, and (3) irrelevant studies (such as correspondence, letter, review, editorial, ecological, experimental, etc.).

Data extraction
For included studies, the following information was extracted by two authors (DP and BM) independently after reviewing the studies based on the inclusion/exclusion criteria: the first author's name, the publication years, the sample size, the average age and standard deviation of stroke patients, the number of water pipe smokers with a history of stroke, OR and corresponding 95% CI stroke patients based on water pipe smoking, and covariates adjusted for relationship.
Any disagreements were resolved by discussion with a third author (HM).

Statistical analysis
The ORs and 95% CIs of stroke in water pipe smokers considered measures of effect size, which was analyzed by the metan package (Harris et al., 2008) in the STATA software version 14.2 (https://www.stata. com) based on standard error and OR from each study.The Q-test and I 2 statistics (Michael Borenstein & Rothstein, 2007) were used to assess the homogeneity between the studies.According to results from these statistics, we applied the fixed (or random) effect model to obtain the pooled OR for stroke patients who have consumed water pipe.Also, to assess publication bias, funnel plot and Egger's regression test for funnel plot asymmetry were used (Begg & Mazumdar, 1994;Egger et al., 1997).The threshold area to reject results was set as 0.05.

Study selection
After implementing the search strategy, a total of 1514 studies were identified.The initial survey showed that 163 studies were duplicated and 1351 studies needed to be further evaluated.A total of 1272 studies were removed after the screening of the study title and abstract.In the next step, 68 excluded for the following reasons: 65 studies were irrelevant or there was no full text, 5 studies were in animal fields, and 2 studies reported the relationship between stroke and water pipe in person year that according to the data presented, OR could not be evaluated.Finally, out of the remaining seven studies, 3 studies were excluded from the study due to the non-extractability of the data or the lack of an appropriate control group.For the final meta-analysis, four studies were included (Figure 1).

Characteristics of studies
In the four eligible studies, there were a total of 2759 participants that 555 patients had at least once experienced stroke.Among the include studies, three studies (El- Hajj et al., 2019Hajj et al., , 2020;;Tabriz et al., 2020) were case-control studies and one study (Farah et al., 2015) was a cross-sectional study.The publication year of one study (Farah et al., 2015) was 2015 and the other three studies (El-Hajj et al., 2019, 2020;Tabriz et al., 2020)  F I G U R E 2 Forest plot of the adjusted relationship between stroke and water pipe smoking.
participants.In all selected studies, the samples included males and females, but the suggested information was not expressed separately for gender.Also, the information was reported in such a way that the ability to calculate the OR between stroke levels (ischemic, hemorrhagic, and transient) and hookah levels (non-smoker, former smoker, and current smoker) were not possible.All of the included studies used a logistic model for analysis and adjusted for confounding factors (age, sex, behavior factors, etc.).Further details are present in Table 1.

Water pipe and overall odds of stroke
From the four eligible studies, the result of the meta-analysis indicated a significant positive relationship between water pipe smoking and stroke (OR = 2.79, 95% CI: 1.74-3.84).Heterogeneity between studies was not statistically significant (I 2 = .00%;p-value = .714),and a fixed-effect model was used in this meta-analysis (Figure 2).

Publication bias
To identify the publication bias funnel plot and Egger regression test were used.The funnel plot shows asymmetry publication bias between the four studies (Figure 3).In other words, there was no statistically significant publication bias between studies based on Egger's regression test for funnel plot asymmetry (t = 2.70; p-value = .114).These results suggest no publication bias existed in this meta-analysis.

DISCUSSION
This meta-analysis represents the first systematic attempt to explore the association between water pipe smoking and the risk of stroke.
Stroke causes 9% of all deaths around the world, which is heavily influenced by various risk factors, including high blood pressure and tobacco use (Donnan et al., 2008).A mere 10 mm Hg increase in systolic blood pressure (or 5 mm Hg in diastolic pressure) can escalated the risk F I G U R E 3 Funnel plot for eligible studies include in meta-analysis.
of stroke by 40% (Law et al., 2009).Consequently, high blood pressure is estimated to account for a significant portion, ranging from 35% to 50%, of the overall risk of stroke (Whisnant, 1996).Moreover, smoking leads to a rise in blood pressure, a consequence attributed to the presence of nicotine and carbon monoxide in tobacco smoke (Omvik, 1996).
Carbon monoxide, a component of smoke, binds to blood hemoglobin, forming carboxyhemoglobin, which subsequently reduces blood oxygen levels (Fauci et al., 2012).Evaluated carboxyhemoglobin levels are associated with increased levels of inflammation-sensitive proteins, such as fibrinogen, haptoglobin, and ceruloplasmin, all of which have established links with cardiovascular disease and stroke.
Specifically, heavy smokers with high inflammation-sensitive protein levels are at a 3.05-fold higher relative risk of stroke compared to non-smokers with low inflammation-sensitive proteins levels (Lind et al., 2004).
The present meta-analysis, drawing from four eligible studies, reveals a substantial impact of water pipe smoking on the risk of stroke (OR = 2.79, 95% CI: 1.74, 3.84).In each of these studies, individuals who suffered strokes had histories of water pipe and cigarette smoking, hypertension, obesity, and diabetes mellitus.Adjusted OR s in these studies considered factors such as sex, age, and underlying diseases.
Furthermore, the absence of heterogeneity and publication bias across these studies lends strength to our findings.
However, it is crucial to acknowledge the limitations of our study.
Notably, the available data did not allow for a dose-response analysis, and we did not assess the long-term effects of water pipe smoking.
Additionally, demographic factors, such as age, sex, and education, were not reported in connection to water pipe smoking in some studies.Moreover, in certain instances, cigarette smoking and water pipe smoking were collectively categorized as "smoking," despite the welldocumented disparities in harm between these two forms of tobacco consumption.Furthermore, there were instances of insufficient detail regarding exposure to water pipe smoke.Finally, all four eligible studies were conducted in the Middle East, which imposes geographical limitations on the scope of our findings.It is essential to recognize that the regional homogeneity of these studies may influence the generalizability of our results.
The popularity of water pipe use, particularly among young individuals, including women, underscores the significant of this issue (Baalbaki et al., 2019).Recent studies indicate a slightly higher prevalence of stroke among women (women: 2.7% and men: 2.6%; about 60% of stroke deaths were attributed to women), and specific factors contributing to strokes in women encompass the use of oral contraceptive pills, pregnancy, preeclampsia, and gestational diabetes among younger women, whereas older women may be at risk due to factors like migraine headaches with aura, atrial fibrillation, diabetes mellitus, and hypertension (Lundberg & Volgman, 2016;Mirzaei, 2017).

CONCLUSION
In conclusion, our analysis revealed that water pipe smoking has a more substantial effect on stroke risk compared to cigarette smoking, with an OR of 2.79.Given the prevalence of water pipe use, particularly among young people, and considering the high risk it poses, particularly to women, we recommend the implementation of policies aimed at controlling the supply of water pipe products in the market and intensifying educational efforts about the health risks associated with water pipe smoking (Lundberg & Volgman, 2016).Additionally, we encourage researchers to differentiate between cigarettes and water pipe smoking in their analyses, and in light of the increasing popularity of water pipes, we advocate for further comprehensive studies to investigate Characteristics of the included studies.
were related to the last 2 years.The sample size of four studies ranged from 174 to 1515 TA B L E 1 Abbreviations: HS, hemorrhagic stroke; IS, ischemic stroke; NR, not reported; SD, standard deviation; TIA, transient ischemic attack.