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:
- 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.
- 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.
- 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.
- 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.
- 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 'Find Completed Research' heading on the DWI website.