Acta Medica Scandinavica. Vol. 178, fasc. 2, 1965
From the Department of Medicine, Karolinska Institutet, at Serafimerlasarettet, Stockholm, Sweden
The marked geographic variation in the distribution of cardiovascular diseases is well-known and often emphasized (4, 10, 11). It has been the impetus to many studies on the possible influence of various environmental factors. One of these factors is the chemical composition of drinking water. Thus, epidemiologic investigations in Japan, the United States and Great Britain have indicated a higher death rate from cerebrovascular and cardiovascular diseases in areas with soft water than in hard water regions (1, 3, 5, 7, 9, 12, 13, 14). High sulphate concentration in the river water in Japan (5, 12) has also been positively correlated to death rate in cerebrovascular disease. In some studies, however, no correlation has been found (6, 8). The matter has been discussed by Schroeder (15), Dingle et al. (2) and others. Gastric cancer has been found more commonly in areas where the water is soft and has a low pH (16). In the present paper we will briefly report on results obtained from Sweden.
The study is based on material from all Swedish towns with more than 25,000 inhabitants, 33 in number, and in addition Visby on the island of Gotland. The distribution within the country is seen in fig. 1, in which also areas with primitive rocks (white) and sedimentary rocks (shaded) are indicated in table I information is given for each town about number of inhabitants, geology, type of water source and some chemical parameters in drinking water as supplied.
From the local water-works we have obtained the available annual mean values for 23 chemical analyses of the finished drinking water supply from 1940 to 1962. Sixteen of these analyses on at least 1 sample a year are required by law for all works. The period thus covered varies from 5 to 24 years (mean 16), the number of samples subjected to routine analyses from 1 to about 50 a year. Some parameters have been excluded because the values are near or below the limit of the analytical method or because they have been determined at too few works. The remaining water parameters are listed in table II.
From Statistiska Centralbyrån, Stockholm, we have obtained the number of inhabitants in the censuses 1950 and 1960, the absolute number of deaths from 19 specific groups of causes and from all causes, for both sexes and the age groups 25—44, 45—64 and 65—74 years separately, for each year during the period 1951—60 in the respective towns, and the mean age-adjusted death rate for the period. The groups of diagnoses are given in table III.
1. Correlations between the various water parameters, and between death rates from various causes and each of the water parameters, were calculated with the aid of a computer.
2. For the age group 25—74 years the death rates from causes 420 and 422 were plotted separately as well as jointly versus total water hardness and concentration of Ca2+. The equations of the corresponding regression lines and the significance of the slope (t-coefficients) were calculated.
3. For the age groups and sexes separately, multiple regression analyses of the death rate from causes 420 and 422 versus six water parameters which were considered to have little interdependence, were made in unselected order with a computer.
4. The ratios of death rates from causes 420/422 were calculated for the 3 largest cities for each year during the period, from the absolute number of deaths in the age group 25—74 years. The same ratios were also calculated for 9 towns with a mean water hardness less than 3 mg CaO/l00 ml and 6 towns with more than 14 mg CaO/l00 ml.
5. The mean death rates from cause 422 were calculated for the periods 1950—55 and 1956—60 and correlated to the mean concentration of Ca2+ for the whole period. The 10-year mean number of inhabitants was, an approximation taken to be the value for 1955.
6. The death rates from causes 420 and 422 in Stockholm for each year were calculated after interpolation of the number of inhabitants between censuses undertaken in 1950, 1955 and l960.
In the tables the following symbols for the degree of significance will be used: * = probably significant, p < 0.05; ** = significant, p < 0.01; *** = highly significant, p < 0.005.
The correlation between the various water parameters is indicated in table IV. Evidently, there is a large group of water parameters varying together; total solids, ignition residue, total water hardness, concentrations of Mg2++, HCO3-, SO42-, Cl-, SiO2, and F-. The concentration of Ca2+ is correlated to total water hardness and concentration of HCO3-, but not significantly related to other factors, MnO4-consumption, an expression of the amount of reducing substances (mainly organic) in the water, tends to vary inversely with the large group of inorganic constituents mentioned above. The pH is significantly correlated only to the concentration of marble-attacking HCO3-.
The results of the correlation between death rates and water parameters (r coefficients) are summarized in table V (males) and table VI (females). Total mortality — death rates from causes not here specified as well as from most of the specified causes — were not significantly related to any of the water parameters. For certain groups of causes, however, e. g. malignant tumours of the upper digestive tract (140—150), vascular diseases (450—468) in the males, and breast cancer (170) in the females, highly significant positive correlations to the inorganic group of water parameters were found (p <0.005). For death rate from cerebrovascular diseases in the females, a probably significant negative correlation was found to the same group of water parameters (p < 0.05). The concentration of Ca was significantly negatively correlated to the death rate from “other degenerative heart diseases” (422) both in males and females. Similar patterns were to some extent obtained in the other age groups.
In the present investigation only the group of cerebrovascular and cardiovascular diseases was studied in some detail. Table VII summarizes the correlation (r-coefficients) to water hardness for all the sex- and age groups. In the youngest male group a highly significant negative correlation (p < 0.005) for water hardness was found with “other degenerative heart diseases” (422), mainly so-called “cardiosclerosis” or “myocardial degeneration”. A significantly negative correlation (p <0.01) was found for cerebrovascular diseases in the middle age group of women. In addition, scattered significances at the p < 0.05 level were seen.
Table VIII shows the correlation coefficients (r) for the death rates from these cerebrovascular and cardiovascular diseases to the concentration of Ca2+. For males a highly significant negative correlation was found to the group of “other degenerative heart diseases” (422) in all age groups (p <0.005). In the females a corresponding correlation increasing with age was noticed: in age group 45—64 years p <0.01, and in the group 65—74 years p <0.005. For none of the sex- and age groups was any correlation found between death rate from arteriosclerotic heart disease (420) and concentration of Ca2+.
The same relation is illustrated in figs. 2 and 3. The death rates from arteriosclerotic heart disease (420) and “other degenerative heart diseases” (422) for the age group 25—74 years, both sexes together, were plotted against total water hardness and concentration of Ca2+ respectively. The slopes of the calculated regression lines are highly significant (p <0.005) for 422 against both water parameters and significant (p <0.01) for 420 against water hardness, but not against concentration of Ca2+.
The multiple regression analysis showed no significant correlation between any of the water parameters (MnO4-consumption, concentrations of Ca2+, HCO3-, SO42, Cl-, and pH) and death rate from cause 420, with the exception of concentration HCO3- in the youngest males. The death rate from cause 422 was found to be significantly correlated to concentration of Ca2+ in all the male groups, and in the youngest group also to Cl- and pH. For the females the death from cause 422 was significantly correlated to pH and concentration of Ca2+ in the middle age group, and to the concentration of HCO3- in the oldest.
These rather startling findings forced us to analyze the group “other degenerative heart diseases” in greater detail.
Table IX shows the actual number and the number as a percentage total mortality, of patients in the various age groups and sexes whose causes of death were registered as arteriosclerotic heart disease and “other degenerative heart diseases”, respectively. On an average the ratio of the diagnoses 420 : 422 in males is 3 : 1, whereas in females it is closer to 3 : 2.
There is, however, a strong tendency in later years towards an increased assignment of 420 in preference to 422. This fact is indicated in figs- 4 and 5. The ratio for the number of deaths from 420/422 in the three biggest cities shows a three- to fourfold increase during the 10-year period, as seen in fig. 4. The plot of the death rate from causes 420 and 422 in Stockholm shows ( fig. 5) that the change in the assignment of the diagnosis numbers refers mainly to the males.
In view of this tendency, it seemed worth while to analyze whether the correlation of mortality from No 422 to low calcium concentration was more marked in the beginning or at the end of the period studied. The results are given in table X. This table substantiates the over-all negative correlation, but unfortunately does not give a definite answer to the said question. Farther studies, therefore, are necessary on this point.
The results presented in a general sense agree with those published from Japan, U.S. and England (5, 7, 12, 13, 14). Once more, in still another part of the world, in a country with a very homogeneous and stationary population, which is reasonably well organized as far as population statistics and water supply are concerned, the very strange fact has been revealed that “water hardness” and some constituents of drinking water associated with water hardness are in one way or another correlated to a specific fraction of the death rate in cardiovascular diseases.
The interpretation of this fact has been discussed in some detail by earlier investigators, and various suggestions e.g. concerning the possible role of certain trace elements deriving from soil or water pipes etc., have been made.
We have great difficulty in explaining why the calcium concentration in water should affect cardiovascular mortality, when the relationship between calcium content of water and of food is considered. It appears to us most reasonable to regard calcium as an “indicator” of something else, which might be a causal agent. Trace metals may be one type of factor that could be operating. Other environmental factors might also play a role. These problems will require further study.
Another aspect which has been brought out by this study is the question of the homogeneity of the statistical group 422 - “other degenerative heart diseases”. This group has long been regarded as a waste-paper basket into which doubtful and difficult diagnostic problems were thrown. Patients not suffering from clear-cut angina pectoris or myocardial infarction, but eventually dying unexpectedly or with heart failure in the absence of valvular heart disease or hypertension, have been referred to this group. Recent puritanism in the diagnostic nomenclature has caused a gradual giving up of that diagnosis in preference to 420 — arteriosclerotic heart disease. And now it turns out that — whatever the causal relationship involved may be — this group 422 repeatedly shows homogeneity in this statistical analysis of fairly large numbers. This is true of our study, but it is also true of the British study (7).
In both studies, the negative correlations with water hardness or calcium ion seem to be stronger for 422 than for 420. If we believe 420 to be a fairly homogeneous group, 422 would also have to be accepted in the same way. And if so — what, then, is the medical significance, the aetiology and the pathogenesis of “other degenerative heart diseases”?
A study has been made on the relationship between deaths from cardiovascular diseases and various parameters in drinking water in 34 Swedish towns during 1951-60.
The figures indicate a highly significant negative correlation between the calcium ion concentration and the statistical group 422 (“other degenerative heart diseases”).
Essentially the findings confirm results of similar studies from other countries. It does also raise the problem of the medical significance of the group 422.
We are indebted to the Swedish Association against Heart- and Lung Diseases for financial support and to Statistiska Centralbyrån for considerable aid in the statistical analysis of the material.
1 CRAWFORD, M. D.: Personal communication 1964.
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Submitted for publication February 23, 1965.
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