Epidemiological evidence on drinking water salinity and blood pressure: a scoping review

In addition to diet, drinking water can be an important contributor to the total body burden of salts. Water salinity (defined as the amount of dissolved salts in a body of water) has been associated with adverse health effects. We mapped the current research on drinking water salinity and its effects on blood pressure (BP). We aimed to identify knowledge gaps in the methodology and tools used in the epidemiological literature to address water salinity effects on BP. We performed a scoping review of epidemiological studies by searching PubMed and Web of Science databases from 1980 to 2022. Reviews, study comparisons, meta-analyses, commentaries, viewpoints, correspondence, protocols, studies in clinical settings, animal or in vitro studies, or not in English, were excluded. Epidemiologic studies including systolic/diastolic BP and/or the risk of hypertension as the main health outcome and drinking water salts (sodium, potassium, calcium, magnesium, including electrical conductivity and total dissolved solids) as the main exposures were included. After screening 246 articles, 29 articles were retained. Most studies were conducted in Bangladesh and USA ( n = 9 and n = 9, respectively). The majority of studies were cross-sectional ( n = 18; 62%). The study populations were adults (55%) or children (35%) or both (10%). Only eight (28%) studies did not collect urine samples and only three studies (10%) did not record participant BP. About half of the studies ( n = 15, 52%) reported a positive significant ( p < 0.05) association between salts in drinking water and higher BP and/or risk of hypertension; while 24% and 24% reported non-significant ( p > 0.05) and significant ( p < 0.05) negative associations (with lower BP mainly attributed to higher Mg, Ca, and K (rather than Na) levels in drinking water).


Introduction
High blood pressure (BP) is a modifiable chronic condition affecting millions of people around the world and it is a key WHO global target to prevent a suite of non-communicable diseases (Nguyen and Chow 2021). Hypertension is responsible for about 50% of all deaths from stroke and heart disease, worldwide (National Organization of Public Health 2021). The systematic consumption of high sodium (Na) diets is a well-known risk factor for the development of hypertension (He and MacGregor 2009, Huang et al 2020, Filippini et al 2021, while high dietary intake of other salts (e.g. magnesium (Mg), calcium (Ca) and potassium (K)) can reduce BP (Houston and Harper 2008, Schutten et al 2018, Wabo et al 2022. Drinking water is an underestimated source of salts, contributing to the total body burden of salts. Nevertheless, the possible contribution of water salinity to the risk of hypertension is unknown. Salinity is the collective term used to characterize the amount of dissolved salts in a body of water (EPA 2022). The major dissolved inorganic solutes in water are Na, Mg, Ca, K, among others. The total concentration of dissolved inorganic solutes in water can be measured using either electrical conductivity (EC) measurements, or with its filtered residue weight upon evaporation to dryness (Rhoades 1996).
The salinity of drinking water associated with groundwater aquifer sources is anticipated to increase in the coming years due to the increased extraction of groundwater for agricultural demand, the increased salinity of surface waters from anthropogenic sodium sources, and the manifestations of global climate change (e.g. rising temperatures and sea level, persistent droughts, etc) (Werner and Simmons 2009, Khan et al 2011, Ramya Priya and Elango 2018, Guimond 2021. Therefore, it is essential to understand the effect of increasing salinity of drinking water on BP. Earlier studies relying upon proxies of drinking water salinity (mainly the metrics of total dissolved solids, TDS, and EC) have demonstrated their association with increased risk of heart disease (Schroeder 1960(Schroeder , 1966. More recent epidemiological studies on the association between drinking water salinity and BP changes have reported mixed results. Some of them have observed a significant positive association between salinity of drinking water and BP (Talukder et al 2016, Talukder et al 2018, while others reported a significant negative association (Rylander and Arnaud 2004, Naser et al 2019b, Naser et al 2020. Consequently, the topic of drinking water salinity changes and their effects on BP is by no means settled or thoroughly explored. An earlier systematic review and meta-analysis found a small association between water Na and BP in epidemiological studies, but it did not include other water salts (Talukder et al 2017).
We conducted a global scoping review to assess the potential size of the current epidemiological research in the area of drinking-water salinity, including Na and other salts (Ca, Mg, and K) and their effects on BP; and to identify the nature and extent of the environmental epidemiological literature relating to drinking water salinity effects on the risk of hypertension.

Methods
A scoping review protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for scoping reviews (PRISMA-ScR) (Tricco et al 2018).

Search strategy and screening
We performed a global literature search of PubMed and Web of Science databases using the following broad search keywords/phrases: "'Sodium OR Magnesium OR Potassium OR Calcium OR Electrical conductivity OR Salinity" AND " drinking water" AND "Hypertension OR BP"' focusing on human species for PubMed and ' (Sodium OR Magnesium OR Potassium OR Calcium OR Electrical conductivity OR Salinity) AND drinking water AND (Hypertension OR BP)' focusing on human for Web of Science. The search strategies were prepared by the lead researcher and finalized through study team discussion. The most recent search was executed on 30 November 2022 in both databases. Also, backward hand-searching of the references cited in the selected articles was conducted.
Eligible articles for inclusion were those human studies published between 1980 and 2022 (30 November 2022) and written in English. Review articles, study comparisons, meta-analyses, commentaries, viewpoints, correspondence, protocols, animal or in vitro studies, studies published before 1980, studies that recruited patients from clinics/hospital settings, and all studies not in English were excluded (figure 1). Both reviewers went through all potential studies (not excluded) and evaluated the titles, abstract and the full text (when necessary) to decide whether they were eligible or not. The search hits were summarized in an excel file by source (PubMed, Web of Science, and cited references in the hits), reviewers, author names, publication year, title, abstract (where available).
The main outcomes considered were the systolic and diastolic BP (SBP and DBP) and/or risk of hypertension, and the main exposures for BP-related outcomes were drinking-water salts (Na, Mg, Ca, K, including EC and TDS). For the selected (eligible) studies, the following columns in the excel were completed: study design, sample size, country, age of participants, study population (specific feature), water sample (collected or not), measurements in water (Na, Mg, Ca, K, EC and TDS), which biological matrices were collected, measurements in biological matrix (Na, Mg, Ca, and K concentrations), BP (recording method and time), temperature (human or ambient air), diet (recording method), other covariates, and main results (excel file, supplementary file).
Selected articles were grouped by their results: positive significant (p < 0.05) association between some salts of drinking water and BP and/or risk of hypertension (table 1); negative significant (p < 0.05) association between some salts of drinking water and BP and/or risk of hypertension (table 2); and non-significant (p > 0.05) association between some salts of drinking water and BP and/or risk of hypertension (table 3), including the study population age groups (adults, both adults and children, or children, <18 years old) (see supplementary information file).
Descriptive summaries of the studies focusing on the aforementioned age groups were prepared on the basis of: study design, publication year, age, sex, and special features of study population (e.g. pregnant), the country where the study took place, type of statistical analysis used (individual-level or group/ecological), the use of water and/or biospecimen samples, the number of BP measurements and time of recording, the participants dietary salt intake, information about the body or ambient air temperatures, and the reported main results. Regarding cohort and randomized controlled trial (RCT) studies, the repeated measures in time/range were also recorded.

Results
In total, 246 hits were identified using the PubMed, Web of Science databases and combined with backward hand-searching in the references of the selected articles. After removing duplicates, 241 articles were retained. A total of 212 publications were excluded, because the eligibility criteria were not met (figure 1), i.e. 13 studies were published before 1980, six were not written in English, five were commentaries, one was viewpoint, one was a study protocol, 37 were review/articles/study comparisons/meta-analysis, 102 were animal studies; a total of 47 studies were not related to the topic: either the main outcomes of these studies were other than systolic and diastolic BP, or the main exposure for BP-related outcomes was not the drinking-water salts, or the main objective was not the association between salts in drinking water and BP, or included patients from clinics/hospital settings. The inter-rater reliability among the two reviewers was satisfactory with correlation coefficient being > r = 0.80. Ultimately, a total of 29 articles were retained and reviewed in detail.

Characteristics of selected studies
The eligible articles were published in English  and examined the association between salts in drinking water (Na, Mg, Ca, K, including EC and TDS) and BP and/or the risk of hypertension in the general population (Hofman et al 1980, Hallenbeck et al 1981, Tuthill and Calabrese 1981, Armstrong et al 1982, Faust 1982, Pomrehn et al 1983, Robertson 1984, Lackland et al 1985, Tuthill 1985, Welty et al 1986, Yang and Chiu 1999, Pomeranz et al 2000, 2002, Nerbrand et al 2003, Rylander and Arnaud 2004  Six articles studied the association between the risk of hypertension and salts in drinking water (Yang and Chiu 1999, Khan et al 2014, Scheelbeek et al 2017, Naser et al 2019b, Shuvo et al 2020, Rosinger et al 2021. Specifically, four of them (Khan et al 2014, Scheelbeek et al 2017, Naser et al 2019b, Rosinger et al 2021 examined both the association between the salts in drinking water and BP and the association between the salts in drinking water and the risk of hypertension, while the rest two articles (Yang andChiu 1999, Shuvo et al 2020) focused solely on the association between the salts in drinking water and the risk of hypertension.

Characteristics of selected studies reporting a positive significant (p < 0.05) association between salts in drinking water and BP and/or risk of hypertension
Overall, 15 studies (52%) reported a positive significant (p < 0.05) association between specific salts of drinking water and BP (either SBP or DBP or both) and/or risk of hypertension (Hofman et al 1980, Hallenbeck et al 1981Tuthill and Calabrese 1981, Tuthill 1985, Pomeranz et al 2000, 2002, Nerbrand et al 2003, Brown et al 2005, Khan et al 2014, Scheelbeek et al 2016, 2017, Talukder et al 2016, Shuvo et al 2020, Naser et al 2021 (table 1). Specifically, the majority of these studies (n = 10; 67%) reported a significant positive association between water Na and BP. One study reported a positive significant association between EC and BP (Naser et al 2021) one study observed a positive significant association between water Ca and SBP (Nerbrand et al 2003). Also, one study observed positive significant association between EC of drinking water and risk of hypertension (Shuvo et al 2020); another study observed that odds of hypertension were lower by 14% with decreasing drinking-water sodium concentrations (100 mg l −1 reduction) (Scheelbeek et al 2017). Finally, one study (Khan et al 2014) showed a positive significant association between water Na and the odds of hypertension 3.30 (95% CI 2.00-5.51), 4.40 (2.70-7.25) and 5.48 (3.30-9.11).
Some studies reported differences in Na levels between study groups/communities. Half of the studies assessed the association between BP and salts in drinking water at the individual level, i.e. the statistical analyses were performed using water salt data obtained for each participant. The rest of studies used drinking water samples collected at the community/school level. The maximum average Na difference in drinking water between study groups was 401 mg l −1 , the minimum difference was 99 mg l −1 , while the average differences was 174 mg l −1 .
In one of the studies which did their analysis at group level, the Na concentration in drinking water in the three study groups was not specified/quantified, but qualitatively reported (long-term low vs long-term high vs short-term high) (Hofman et al 1980).

Characteristics of selected studies reporting negative significant (p < 0.05) association between salts in drinking water and BP and/or risk of hypertension
A total of seven (24%) studies reported significant negative (p < 0.05) association between drinking water salts (Na, Mg, Ca, K, including EC) and BP and/or risk of hypertension (Lackland et al 1985, Yang and Chiu 1999, Rylander and Arnaud 2004, Rasic-Milutinovic et al 2012, Naser et al 2019b, Naser et al 2019a, Naser et al 2020 (table 2). One (Lackland et al 1985) study measured Na in drinking water, one (Naser et al 2019b) measured the EC of drinking water; two studies (Yang andChiu 1999, Rasic-Milutinovic et al 2012) measured levels of Ca and Mg in drinking water; two (Rylander andArnaud 2004, Naser et al 2020) measured all salts in drinking water (Na, Mg, Ca, K) and one study (Naser et al 2019a) used data available for 11 ground water salts, including Na, Mg, Ca, and K.
In detail, two studies reported negative association between Mg in drinking water and BP (Rylander andArnaud 2004, Naser et al 2019a) and one study (Lackland et al 1985) observed negative association between Na in drinking water and BP. Also, one study (Naser et al 2019b) observed that mild salinity of water using EC (EC: 0.7-2 mS cm −1 ) would reduce BP. The same study observed that the adjusted odds ratio of stage 1 and stage 2 hypertension among mild-salinity water drinkers was 0.60 (95% CI: 0.43,0.84) and 0.56 (95% CI: 0.46-0.89). At the same time, a cohort study (Naser et al 2020) observed that the consumption of low-salt water (Na = 2.36; K = 1.8; Ca = 2.30; Mg = 1.21 mg l −1 ) was associated with worsening cardiometabolic health outcomes. An RCT study (Rylander and Arnaud 2004) showed that the BP of participants was reduced for those consuming natural mineral water (Na = 9.1; K = 3.1; Ca = 486; Mg = 84 mg l −1 ), but this was not the case for the groups consuming low in minerals water (Na = 1.9; K = 0.2; Ca = 68; Mg = 2 mg l −1 ) and for the group consuming Mg-enriched water (Na = 2.4; K = 0.1; Ca = 4; Mg = 82 mg l −1 ). Finally, one study observed significant protective effect of magnesium intake from drinking water on the risk of hypertension (Yang and Chiu 1999).
About half of them used analysis at individual level (n = 4; 57%) and were cross sectional (n = 3; 43%). Three studies (Rylander and Arnaud 2004, Naser et al 2019b, Naser et al 2020 (43%) collected urine samples (24 h). Except for one (Naser et al 2019b), none of these studies (86%) recorded the time of the day that BP measurements took place. Also, no study collected data about air temperature (human or ambient air) and only two studies (Lackland et al 1985, Naser et al 2020 (29%) included information about dietary sodium intake.
3.4. Characteristics of selected studies reporting non-significant (p > 0.05) association between salts in drinking water and BP and/or risk of hypertension A total of seven (24%) studies reported no significant (p > 0.05) association between some salts in drinking water and BP and/or risk of hypertension (table 3) (Armstrong et al 1982, Faust 1982, Pomrehn et al 1983, Robertson 1984, Welty et al 1986, Rosinger et al 2021. Most of these studies (Armstrong et al 1982, Faust 1982, Pomrehn et al 1983, Robertson 1984, Welty et al 1986) (n = 6; 86%) observed non-significant association between Na in drinking water and BP, they were published before 2000 and they were cross sectional. There was a single study that looked into the association between drinking-water salinity and BP, albeit non-significant (Rosinger et al 2021). Except for one study (Welty et al 1986), all studies (86%) assessed the association between BP and salts in drinking water at the group level. Interestingly, a non-significant (p > 0.05) association between drinking-water salinity and systolic and diastolic BP was observed in linear regression models for each additional 100 mg l −1 of drinking water salinity, but instead a significant (p-value = 0.010) association was observed when the risk of hypertension was used in logistic regression models (Rosinger et al 2021).
One study did not collect urine samples  and two studies (29%) collected urine samples only from boys (specimen of urine and 24 h urine samples) (Armstrong et al 1982, Robertson 1984. The rest of the studies collected either overnight urine samples (n = 2; 29%), 24 h urine samples (n = 1; 14%), or spot urine sample (n = 1; 14%). Except for one (Rosinger et al 2021), all studies (86%) collected data on diet. The time window of the day during which BP measurements were taken was reported by four studies (57%) (Pomrehn et al 1983, Robertson 1984, Rosinger et al 2021. Three studies (43%) included information about temperature (human or ambient air) in their analysis (Armstrong et al 1982, Pomrehn et al 1983, Rosinger et al 2021. The association between BP and Na in drinking water was examined using stepwise multivariable regression models of SBP/DBP (Pomrehn et al 1983) (Welty et al 1986), correlation analyses (Armstrong et al 1982, Faust 1982, or analysis of covariance  and F-test (Robertson 1984). Notably, the methodology of these studies was not elaborated in adequate detail.

Discussion
This scoping review builds upon the epidemiological evidence of association between drinking water salts (Na, Mg, Ca, K including EC and TDS) and BP that were earlier captured in a systematic review and meta-analysis (Talukder et al 2017). The earlier review studied the association between water Na and BP in ten human studies published in English from 1960 to 2015; they documented a small positive association between water Na and BP (Talukder et al 2017). This current scoping review went a step further and updated such findings with more recent studies, while including other drinking water salts in the search strategy (Mg, Ca, K, EC and TDS).
The total number of selected studies (n = 29) was relatively small, if we consider that the period that these studies were published, spanned a range of >40 years. The majority of them used a cross-sectional study design or outcomes were evaluated over very short timescales highlighting the need for longitudinal data with extensive spatiotemporal coverage. Overall, there was limited methodological and statistical description in the studies published before 2000, while important confounders of BP and drinking water salts (e.g. ambient air temperature and timing of BP measurements) were missing in most studies. Also, most of the publications were conducted in the Bangladesh and the USA; however, water salinization is a global environmental change process and there are other affected settings and populations, particularly in coastal areas where salinization perturbations have been reported, and/or associated health evidence is lacking.
No children's health studies on this topic were found after 2002. During the period 2001-2022, a total of 16 studies were published with only two of these studies focusing on children's health. The remaining 14 studies were conducted among either adults or both adults and children, with more than half (n = 9, 56%) of them being carried out in Bangladesh. Although most studies included both sexes, less than half of the studies conducted stratified analysis to assess the effect of sex on the association between BP and salts in drinking water. Also, the majority of the studies conducted analysis at the group level (n = 16).
Significant positive association (p < 0.05) between some salts of drinking water and BP was observed in most studies. Specifically, 15 of the 30 studies observed positive significant association between either Na (n = 11), EC (n = 3), or Ca (n = 1) in drinking water and BP. These studies were conducted in Sweden, USA, Israel, Switzerland, Netherlands and in coastal Bangladesh. Seven studies observed a negative significant association (p < 0.05) between salts in drinking water and BP. Except for one study that measured the Na concentration of drinking water and observed a negative significant association between the Na concentration of drinking water and BP, all studies suggested that the significant negative association between salts in drinking water and hypertension risk was attributed to higher Mg, Ca, and K levels in drinking water. A non-significant association between drinking water salts (Na and TDS) and BP was observed in seven studies. Most of these studies used simple descriptive statistics and did not describe their methodology and tools in detail.
From 2014 onwards, a total of nine studies conducted in coastal areas (Bangladesh, n = 7; Kenya, n = 1) mentioned in-text the role of climate change in altering drinking water salinity levels. Four of these eight studies measured the EC in drinking water, one study measured the salinity in drinking water, and three studies measured only the Na in drinking water. The studies that measured the EC and TDS in drinking water showed mixed results, with three of them reporting a positive significant association between increased of EC and BP. One study observed that mild salinity in drinking water could reduce the BP level. One study reported non-significant association between TDS and BP. At the same time, the studies that measured all salts in drinking water suggested that the consumption of low-salt water would affect BP levels. All studies that measured Na in drinking water observed positive significant association with BP, but did not take into account the concentrations of other salts (Mg, K, Ca).
Ambient air temperature measurements in the selected studies was used as confounder in the relationship between water salinity and BP. It is well known that low temperature may increase BP (Radin et al 2018): low temperatures cause vasoconstriction, while high temperatures cause vasodilation (Johnson et al 2014). Also, water salinity levels may increase as a result of enhanced evapotranspiration phenomena during the warmer periods of the year. Heat stress is a major manifestation of climate change impacting the body's physiological functions, such as the ability to regulate its internal temperature (Hajat et al 2017). Increased ambient air temperatures have been associated with premature mortality for a series of renal, cardiovascular, respiratory, and infectious disease outcomes (Basagana et al 2011).
This work showed the limitations and research gaps of the global literature in the field of water salinity and BP effects. First, we identified large knowledge gaps relating to the relationship of drinking water salinity and BP with significant ramifications for public health. Second, it became apparent that this is a relatively new area of research; all included studies were published between 1980 and 2022, with one third of them being published during the last 7 years (2016-2022). The recent increase in research on the cardiovascular effects of drinking water salinity under a changing climate is worth mentioning, but more work is needed. Third, most studies in this scoping review were conducted in the Bangladesh and the USA, documenting a gap of knowledge for such salinity-DP associations in other areas of the globe.
A recent systematic mapping of research on climate and health revealed that air quality and heat stress were the most frequently studied exposures, with all-cause mortality and infectious disease incidence being the most frequently studied health outcomes (Berrang-Ford et al 2021). Also, the recent systematic mapping showed a gradient of increasing focus on chronic disease rather than on infectious diseases in high income countries; whereas in lower-, and middle-income countries, infectious diseases seem to dominate the literature on climate and health (Berrang-Ford et al 2021). More robust, independent research examining the cardiovascular effects of increasing drinking water salinity and its major components (Na, Mg, K, Ca) are greatly needed for coastal populations and large urban centers in the coastline around the globe.

Limitations
The fact that we studied articles published in English language is an important limitation of our scoping review. Another limitation was the fact that we excluded studies where salts/BP were not included as a primary outcome. Also, although the end-point search date was 30 November 2022, some records would experience a delay before properly being indexed in databases, thus, missing some of them in our search. Another limitation would be the fact that studies recruiting patients from clinics/hospital settings were excluded.

Implications
The implications of this review analysis are very important, as ongoing climate change manifestations via sea level rise continue to threaten the resilience of groundwater bodies near coastal zones. The attainment of safe drinking water for all is challenged by global environmental change processes impacting water quality, particularly in coastal areas. About half of world population uses groundwater as a drinking water source, while about two-thirds of the world's cities with populations of over five million are in coastal areas at risk of sea level rise (United Nations 2017). This may be exacerbated in coastal areas where large urban centers are located. The issue of salinization is particularly relevant to the Sustainable Development Goal 6 and public health, including the contribution of the UN Decade of Ocean Science for Sustainable Development to the Achievement of the 2030 Agenda (UNESCO 2022).
In addition to USA, Bangladesh, Kenya and Vietnam where most selected studies for this scoping review took place, there are several other coastal areas around the globe that are vulnerable to climate change manifestations, such as seawater intrusion into groundwater aquifers (Cai et al 2021). This may be attributed to global climate change phenomena (e.g. rising temperatures, droughts and rising sea levels) coupled with the overexploitation of groundwater for agricultural purposes. Globally, the salinity of drinking water associated with coastal groundwater aquifers is anticipated to significantly increase in the coming years.
From a public health practitioner perspective, small BP changes at the population level matter. The BP reduction as a means to prevent and control hypertension at the population level has been demonstrated in large epidemiological studies and cost-effectiveness analyses as an effective public health intervention strategy (IOM 2010, WEF/WHO 2011). Even within normal BP ranges, population-level decreases in systolic BP may provide benefits for cardiovascular disease (Rahimi 2014, Cheng et al 2023. In effect, the large-scale analysis of randomized trials showed that a 5 mm Hg reduction of systolic BP reduced the risk of major cardiovascular events by about 10%, even at normal or high-normal BP values (Rahimi et al 2021).
In an analogy to the lead-IQ points association paradigm that led to the mass scale removal of lead (Pb) from gasoline, there is a similar story here as well; a small reduction in BP is associated with population-level benefits, even if clinically insignificant at individual level (Stamler 1991). In effect, data from five large epidemiological studies on salt reduction and cardiovascular risk have shown that for each 2 mm Hg difference in systolic pressure, the estimated difference was 4% in coronary mortality, 6% in stroke mortality, and 3% in all deaths (Stamler 1991); this 3% lower total mortality risk for the population aged 45-64 years of age would mean about 12 000 fewer annual deaths just in that age range. A Chinese study showed that a 4/2 mm Hg reduction in population BP changed the hypertension prevalence by 16.6% (Fan et al 2020).

Conclusions
The results of this scoping review call for more longitudinal research to better understand the effects of salinity (salinization) of drinking water on the risk of hypertension. Global ecological drivers of planetary health (including rising sea levels and ambient temperatures) may impact upon the coastal area/freshwater interface and the composition of nearby groundwater aquifers, including their water salinity content. To date, these important global environmental changes and their potential effects on human health have received little attention. This may be particularly important for vulnerable subpopulation groups residing in coastal areas, such as persons living in poverty, workers, children and the elderly, because the climate crisis disproportionately affects the most vulnerable sociodemographic groups.

Data availability statement
No new data were created or analyzed in this study.

Funding
K C M would like to acknowledge funding from internal funds of the Cyprus international Institute for Environmental and Public Health.