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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other: Reliability scoring for regulatory purposes is not applicable

Data source

Reference
Reference Type:
publication
Title:
Magnesium and calcium in drinking water and death from acute myocardial infarction in women.
Author:
Rubenowitz, Axelsson G & Rylander R
Year:
1999
Bibliographic source:
Epidemiology 10 (1) 31 - 36.

Materials and methods

Study type:
case control study (retrospective)
Endpoint addressed:
repeated dose toxicity: oral
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Case-control study investigating the levels of calcium in drinking water and death from acute myocardial infarction among women. The study population encompassed 16 municipalites in southern Sweden. Cases were women who had died from acute myocardial infarction between the ages of 50 and 69 years during 1982-1993 (N = 378) and control were women who had died from cancer (N = 1368). Magnesium and calcium concentrations of the individual water sources were obtained. The subjects were divided into quartiles and odds ratios were calculated.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : Calcium present in drinking water

Method

Type of population:
general
Ethical approval:
not specified
Details on study design:
The study was conducted in an area of southern Sweden where the water magnesium and calcium levels vary between and within municipalities. A questionnaire was sent to all municipal offices asking about drinking water hardness, acidity and water treatment quality. 16 municipalities were identified in which the water quality had been basically unchanged since 1980.
Data was obtained from the National Central Bureau of Statistics on all women in the study area who had died between the ages of 50 and 69 years during the period 1982 - 1993, considering women with a diagnosis of acute myocardial infarction as cause of death. Controls were women with a diagnosis of cancer as the underlying cause of death.
Parish population registers were used to obtain the addresses of the study subjects. Information was obtained from the municipalities on the waterworks that supplied the drinking water to each of the addresses or whether the person used a private well, which gave 378 cases and 1368 controls.
Within the municipalities the number of waterworks included in the study varied between 1 and 17, and the total number was 80.
The subjects were divided into quartiles according to the levels of magnesium, calcium and calcium/magnesium ratio in the drinking water. The crude odds ratios with 95 % confidence intervals, as well as the odds ratios adjusted for age and calcium and magnesium respectively.



HYPOTHESIS TESTED: The relationship between water magnesium and calcium levels, and death from acute myocardial infarction in women.

METHOD OF DATA COLLECTION
- Type: Record review and Questionnaire.
- Details: A questionnaire was sent to all 37 municipal offices in two of the counties in the area (Skane and Blekinge excluding the city of Malmo) on drinking water hardness, acidity, and water treatment procedures. Sixteen municipalities were identified in which the water quality and treatment was unchanged (change of hardness, < 10 %, and change of pH, < 5 %) since 1980. Information on all women in the study area who had died between the ages of 50 and 69 years during the period of 1982-1993 was obtained from the National Central Bureau of Statistics. Parish population registers were used to obtain the addresses of the study subjects. Information was obtained from the municipalities on the waterworks that supplied the drinking water to each of the addresses or whether the person used a private well.

STUDY PERIOD: 1982-1992

SETTING: Southern Sweden

STUDY POPULATION
- Total population: 492 cases and 1706 controls
- Selection criteria: Women were selected based on their cause of death and their age. Women in the municipalities who's underlying cause of death was acute myocardial infarction (ICD 410), aged between 50 and 69 who had died during the period of 1982-1993 were selected for study. Women were excluded from the study if their water was sourced from a private well or neither the address nor the water source could be traced.
- Total number of subjects participating in study: 378 cases and 1368 controls
- Sex/age: All subjects were women aged between 50 and 69 at their time of death.

COMPARISON POPULATION
- Type: Control or reference group
- Details: The controls consisted of women with the diagnosis of cancer (ICD codes 140-239) but were matched on the other parameters.

HEALTH EFFECTS STUDIED
- Disease(s): acute myocardial infarction
- ICD No.: 410
- Year of ICD revision: 1997, 9th Revision
- Diagnostic procedure: Diagnoses were based on death certificates. Autopsies were carried out on 41 % of cases and 16 % of controls; hospital examination before death occurred in 47 % of cases and 83 % respectively; and medical examination outside the hospital before death or examination after death occurred in 8 % and 3 % of cases respectively.
Exposure assessment:
estimated
Details on exposure:
TYPE OF EXPOSURE: Oral exposure, through drinking water

TYPE OF EXPOSURE MEASUREMENT: Questionnaire to municipalities (37 offices)

EXPOSURE LEVELS: Please refer to table 1 for calcium and magnesium levels in drinking water

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: The subjects were divided into quartiles according to the levels of magnesium, calcium, and magnesium/calcium ration in the drinking water.
Statistical methods:
The crude odds ratios (ORs) with 96 % confidence intervals (CIs), as well as the ORs adjusted for age and calcium and magnesium respectively. The latter were calculated using a logistic regression model.

Results and discussion

Results:
FINDINGS

STATISTICAL RESULTS
- OR (Odds ratio): Odds ratios for the whole calcium group were lower in all three quartiles, compared to the referent quartile. Adjustments for age and magnesium altered the odds ratios only slightly. Odds ratios were farther from the null for those of lower age. For the quartile with the highest calcium values, the odds ratio was 0.45 (95 % CI = 0.14 - 0.87) for the younger group and 0.74 (95 % CI = 0.51 - 1.08) for the older group. Odds ratios in relation to the magnesium/calcium quotient showed no notable pattern nor any important difference in effect between the age groups.
The findings indicate that calcium in drinking water may prevent death from acute myocardial infarction among women.
Confounding factors:
The study had no data on other risk factors for acute myocardial infarction. It is unlikely that the amount of magnesium and calcium in drinking water would covary with other risk factors. This could have been the case if densely populated areas, which are usually associated with a higher presence of risk factors such as smoking and stress, had low levels of magnesium in the most densely populated areas varied between 1.3 and 18.6 mg/L, and calcium varied between 30 and 130 mg/L. The municipalites were all median sized and located within a relatively small geographical area, and the levels of magnesium and calcium were different not only between but also within the municipalities. The controls were women who had died from cancer to reduce confounders. For several common diseases such as cerebrovascular and respiratory disease, there are data showing a possible relation with magnesium. These were excluded as control diagnoses, as well as diseases of the digestive organs, because of possible interference with the absorption of magnesium and calcium. Accidental death was also excluded as many cases of accidental death are related to alcohol and alcohol affects magnesium status. Of the diagnoses that remained 85 % had some form of cancer. No clear evidence exists that magnesium affects the risk of death from cancer.
Strengths and weaknesses:
For the clinical diagnosis of acute myocardial infarction strict criteria have to be fulfilled, so the risk of misclassification should be small for those examined in the hospital before death.

Any other information on results incl. tables

Table 2: Calcium in drinking water in relation to number of myocardial infarction cases and controls*

Median calcium

concentrations

(mg/L)

Age

groups

No. of

cases

Number of

controls

OR

95 %

CI

OR †

95 %

CI

≤ 31 quartile‡

 

 

 

 

 

 

 

28

All

129

339

1.0

 

1.0

 

28

50 – 59 years

20

108

1.0

 

1.0

 

28

60 – 69 years

109

231

1.0

 

1.0

 

32 - 45 quartile

 

 

 

 

 

 

 

38

All

79

366

0.57

0.41 – 0.78

0.61

0.39 – 0.94

38

50 – 59 years

10

131

0.41

0.19 – 0.92

0.39

0.13 – 1.14

38

60 – 69 years

69

235

0.62

0.44 – 0.89

0.67

0.41 – 1.08

46 - 69 quartile

 

 

 

 

 

 

 

57

All

88

325

0.71

0.52 – 0.97

0.71

0.49 – 1.02

56

50 – 59 years

13

100

0.70

0.33 – 1.49

0.68

0.28 – 1.65

58

60 – 69 years

75

225

0.71

0.50 – 1.00

0.72

0.48 – 1.08

≥ 70 quartile

 

 

 

 

 

 

 

85

All

82

338

0.64

0.47 – 0.87

0.66

0.47 – 0.94

85

50 – 59 years

8

115

0.38

0.16 – 0.89

0.35

0.14 – 0.87

85

60 – 69 years

74

223

0.70

0.50 – 1.00

0.74

0.51 – 1.08

* ORs with 95 % CIs for death from myocardial infarction among women aged 50 - 69 years.

† ORs adjusted for age and magnesium.

‡ referrent quartile.

Table 3: Magnesium/calcium ratios in drinking water in relation to number of myocardial infarction cases and controls*

Median magnesium/calcium

concentrations

(mg/L)

Age

groups

No. of

cases

Number of

controls

OR

95 %

CI

≤ 0.075 quartile

 

 

 

 

 

0.067

All

76

308

1.0

 

0.067

50 – 59 years

12

111

1.0

 

0.067

60 – 69 years

64

197

1.0

 

0.076 – 0.118 quartile

 

 

 

 

 

0.103

All

122

367

1.35

0.97 – 1.86

0.103

50 – 59 years

15

108

1.28

0.58 – 2.87

0.103

60 – 69 years

107

259

1.27

0.89 – 1.82

0.119 – 0.205 quartile

 

 

 

 

 

0.140

All

86

338

1.03

0.73 – 1.46

0.144

50 – 59 years

10

113

0.82

0.34 - 1.97

0.140

60 – 69 years

76

225

1.04

0.71 – 1.53

≥0.206 quartile

 

 

 

 

 

0.275

All

94

355

1.07

0.77 – 1.51

0.361

50 – 59 years

14

122

1.06

0.47 – 2.39

0.262

60 – 69 years

80

233

1.06

0.72 – 1.55

* ORs with 95 % CIs for death from myocardial infarction among women ages 50 - 69 years.

† referent quartile.

Applicant's summary and conclusion

Conclusions:
The findings indicate that both magnesium and calcium in drinking water may prevent death from acute myocardial infarction among women, and the effect might be more pronounced for lower age groups.