Review of evidence for relationship between incidence of cardiovascular disease and water hardness
DWI0844
October 2005

Executive summary
Summary statement
The literature examining the association between drinking water hardness and cardiovascular disease was identified and reviewed, however a comparatively small
proportion of these studies were considered of high quality. This review found evidence to support a protective effect of drinking water hardness against
cardiovascular disease from a number of studies. If a causal association is established, the comparatively small reduction in cardiovascular risk seen with higher
levels of water hardness, calcium and magnesium concentrations may translate to a substantial public health benefit at the population level. At present there is
insufficient evidence to elucidate the nature of this apparent effect, with significant inverse associations seen with both drinking water calcium and magnesium and
cardiovascular disease. There is also insufficient evidence to make any substantive conclusions regarding drinking water hardness and non-cardiovascular health
outcomes.

Background and purpose

A large body of literature has amassed over a 40 year period examining the apparent inverse association between drinking water hardness and cardiovascular disease in a number of countries. Cardiovascular disease is the leading cause of death in industrialised nations responsible for approximately 235,000 deaths in the UK in 2004. Furthermore, recent studies have begun to examine more diverse non-cardiovascular health outcomes, specifically cancer. Therefore the possible association between drinking water hardness and health outcomes is of great interest given the widespread exposure of the population and the capacity for modification of drinking water hardness levels. Renewed interest in the possible health effects of drinking water hardness has culminated in a series of recently commissioned reviews by the World Health Organisation (WHO).

This study was commissioned by the Drinking Water Inspectorate to review and critically assess the quality of available studies examining the health effects of soft
water, primarily the long standing apparent inverse association between water hardness and cardiovascular disease. This review exceeds that undertaken by the
WHO with regard to both the consideration of a wider range of primary data papers, and a greater focus upon a systematic assessment of the quality of each study  informing the conclusions of this review.

The scope of this review was restricted to an evaluation of the currently available data reporting upon aspects of drinking water quality, specifically hardness, calcium, magnesium, cadmium and lead, and cardiovascular health and other health outcomes. The purpose of this document is to provide an evaluation of the evidence base for policy makers, but not to comment upon any potential policy implications or to recommend any particular course of action.

Objectives

To this aim, the objectives of this study were to:
  1. Review and critically assess the merits of available studies concerning the health effects of soft and softened water and to categorise the identified studies based on  relevant features such as size, study design, conclusions, etc.
  2. Advise on the evidence relating to the incidence of cardiovascular disease, or other adverse health effects to consumption of soft or softened water and to comment on  the reliability and strength of any reported associations.
  3. Advise whether the studies indicate a “no effect” level in relation to water composition and whether a causal or protective agent relating to incidence of     illness is evident.
  4. To comment on whether the results indicate the need to consider re-hardening of softened water, or whether supplies of naturally soft water should be hardened and provide an indication of the scale of the health benefits of such action.
  5. To comment on the evidence relating to specific postulated causal (lead, cadmium) or protective (calcium, magnesium) elements and their importance with respect to cardiovascular disease
Methods

A standardised search strategy was devised encompassing drinking water hardness, calcium, magnesium, cadmium and lead together with all aspects of cardiovascular disease and cancer as major search terms. We searched available electronic databases including MedLine, PubMed, EMBASE, CINAHL, Toxline, Web of Science and Cochrane Reviews. We also searched the Grey literature using the SIGLE database and the National Research database. The initial search identified 2096 papers, the abstracts of which were then independently screened for relevance by two reviewers. Papers were retained if they presented primary data of human studies, were directly related to the research question and involved a comparison of populations or individuals at different levels of exposure. Experimental animal studies and human dietary studies were excluded from this review. Overall, 132 studies were identified as primary data papers, of which 17 papers were excluded due to their descriptive but non-analytical content. A total of 115 underwent full article appraisal by two independent reviewers.

Standardised forms for data extraction and study quality assessment were created to extract information including study population characteristics, exposure
characterisation, sample size, validity of the health outcome and quality of statistical analysis. Separate forms were constructed and used for assessment by
epidemiological study type (ecological, cross-sectional, case control and cohort).

Due to the significant level of clinical and methodological heterogeneity, no attempt was made to assess for evidence of statistical heterogeneity. Data were presented in tabular form with a narrative synthesis of the results presented with no formal meta analysis.

Results

Ecological studies
Most of the published data relate to the possible association between cardiovascular mortality and water hardness, calcium or magnesium levels. The majority of studies reviewed were of an ecological study design. Further study quality criteria were applied to categorise the ecological studies by high, medium or low quality. A total of 60 such papers were evaluated, of which 44 met the minimum quality criteria. Of the 12 high quality studies, 9 presented evidence for a significant inverse association between water hardness, calcium and/or magnesium levels and cardiovascular mortality. The remaining 3 studies found no significant association. Of the 32 medium and low quality studies, 22 found a significant inverse association.

Cross-sectional studies
Five cross sectional studies were identified, of which only 2 sampled the drinking water quality at the individual level with the remainder using an ecological measure of the drinking water parameters. These papers examined individual level cardiovascular risk factors with an inverse association between drinking water
calcium and/or magnesium and blood pressure and serum lipids observed in some, but not all studies.

Case control studies
Six case control studies examined both drinking water magnesium and calcium and risk of death from cardiovascular disease. Of these, 4 found a significant inverse association with magnesium concentrations.

Cohort studies
Of 3 cohort studies reviewed, 2 were of medium/poor quality and used an ecological measure of drinking water factors and limited or non-existent controlling for possible confounders. The third study was conducted in Great Britain and found no association between drinking water hardness and cardiovascular disease. However this study also suffered from poor exposure characterisation.

Sudden death
It has been suggested that the inverse association seen between cardiovascular disease mortality and water hardness may be due to an increase in the proportion of sudden deaths in areas of soft water. Few studies specifically examined sudden death. Our study quality assessment identified only one high quality case control study which demonstrated a protective effect of drinking water magnesium against the risk of death following a heart attack, but not for the risk of a heart attack overall. This is suggestive of a decreased risk of cardiovascular mortality rather than cardiovascular disease incidence overall with increasing drinking water magnesium. To date there is insufficient evidence available upon which to base any conclusion regarding the possible role of sudden death in the inverse association described between drinking water hardness and cardiovascular disease.

There was no evidence to suggest a differential effect of the association between drinking water quality and heart disease or stroke. Whilst evidence has been reviewed supporting a protective role of drinking water quality against atherogenesis, high blood pressure and possibly electrical instability, too few studies have sufficiently examined the possible biological mechanism of association as it may relate to existing major cardiovascular risk factors. The evidence to date is therefore too weak and inconsistent to allow any firm conclusions to be drawn regarding the possible biological mechanism linking drinking water quality and cardiovascular disease. Furthermore, the evidence at present does not support a ‘no effect’ level.

Non-cardiovascular health outcomes
A total of 15 studies examined the association between drinking water hardness, calcium or magnesium and non-cardiovascular health outcomes. Of these, 13
considered cancer as the health outcome of interest and provided evidence for a possible protective effect of drinking water hardness, calcium and magnesium against several malignancies. However, of these 15 studies, 12 were case control studies conducted by a single group in Taiwan. Therefore replication of the results in other settings and centres will be necessary before causal inference can be attempted. As yet, no substantive conclusions can be made in this emerging area of research.

‘Protective’ vs ‘harmful’ effect of drinking water hardness
A number of biologically plausible hypotheses have been reported attempting to identify a single protective factor (dominantly calcium or magnesium) or harmful
factor (dominantly cadmium or lead) associated with varying drinking water hardness to explain the apparent inverse association between hardness and cardiovascular disease. The current evidence based upon the epidemiological studies reviewed here shows a weight of evidence to support the role of a ‘protective’ factor in drinking water. However it must be acknowledged that the small numbers of studies examining possible ‘harmful’ factors may be influenced by publication or reporting bias. A significant inverse association between both drinking water calcium and magnesium was reported by a number of studies considered in this review. However, at present there is not enough evidence of a sufficient quality to identify any factor responsible for the apparent cardioprotective effect of hard drinking water.

Study quality

This review found that although there was a large volume of literature examining drinking water hardness and cardiovascular disease, only a small proportion of the studies were deemed to be of high quality. Therefore even though the methodologically superior cohort and case control studies have examined the
association between drinking water hardness and cardiovascular disease, a common criticism of study quality was poor characterisation of the actual exposure of interest. The majority of individual level studies, including the cohort studies, applied an ecological measure of drinking water quality to the individual level data in the analysis of exposure and outcome. Furthermore, some cohort studies were limited in their examination of potential confounding factors.

Prospective cohort studies are the methodological ideal for the examination of a causal association between an exposure and a health outcome. However, the lack of well designed cohort studies in the literature means that the conclusions of this review must be informed by high quality, but methodologically inferior, studies.

Future directions

This assessment highlights that although there is a large body of literature examining the association between drinking water hardness and cardiovascular health, there has been a lack of focus upon examination of key issues such as temporality and investigation of a possible dose-response relationship on scales of health effects. Epidemiological studies to date are therefore deficient in their ability to contribute to an assessment of causality. A major challenge for future studies attempting to establish a causal association between drinking water parameters and cardiovascular health is the accurate quantitative and qualitative characterisation of individual exposure and the biologically relevant dose. More focused research at the individual level is required to address the deficiencies of the studies to date.

Whilst prospective cohort studies are the ideal for examining causal associations, they are also resource intensive and costly. Other possible options for future study include those able to consider the direction of association, such as those examining a change in the hardness of a public drinking water supply and subsequent changes in health outcomes in a defined population.


Copies of this report may be available as an Acrobat pdf download under the 'Post 2000 Reports' heading on the DWI website.