Serum Parameters in Hard and

Transcription

1 A comparison is made of serum parameters in two similar populations in the hard water communities of Omaha, Nebraska, and London, England, and the soft water communities of Salem, North Carolina, and Glasgow, Scotland. Serum cholesterol levels were diet related and higher in Omaha ( ) and London ( ) than in their soft water counterparts, Salem (228 ± 46) and Glasgow ( ). Serum triglycerides were 14% higher in London than in Glasgow. Nevertheless, lower cardiovascular mortality rates were found in the hard water areas than in the soft water areas and were inversely related to the serum Mg and Ca. Serum Parameters in Hard and Soft Water Communities Introduction The relationship between cardiovascular disease and the mineral content of drinking water has received attention from investigators throughout the world with increasing frequency and interest. Following the stimulating monograph by Kobayashi,' Schroeder2 in 1960 reported a negative correlation between cardiovascular disease mortality rates in the United States and the level of hardness of water. This negative correlation-the harder the water the lower the mortality rate from cardiovascular disease-was confirmed by Morris et al.3 in England and Biorck et al.4 in Sweden. An analysis by Crawford and Crawford5 of autopsy data in London and Glasgow suggested that there was an increased susceptibility of the myocardium to arteriosclerosis among men living in Glasgow, the soft water area. Robertson6 subsequently found that the effect of softening on part of a water supply by replacing calcium ions with sodium ions was significant enough after seven years to see a higher cardiovascular mortality rate in the community receiving the softened water, and suggested that this might be related to the lower calcium content. Morris3 had found earlier an association more with calcium than with hardness. In addition, Fleischman et al.7 showed that calcium in a poorly absorbable form has a significant hypolipemic effect, possibly the result of interference with absorption of fat and cholesterol and the fecal excretion of bile acids. An alternative or additional mechanism was offered by Anderson,8 who suggested that the higher cardiovascular mortality in the soft water area was primarily related to sudden death and might have resulted from lower serum calcium levels leading to increased myocardial irritability, arrhythmia, and death. This intriguing possibility received considerable support from the report of Rodstein et al.9 which showed the higher sudden death rate of members of an insured population previously demonstrating premature ventricular contractions on the electrocardiogram at the time of initial examination. In an extensive review, Masironi'0 suggested several additional mechanisms including the possibility of some toxic factors in the soft water supply which might be Marvin L. Bierenbaum, M.D.; Alan 1. Fleischman, Ph.D.; J. P. Dunn, M.D.; Thomas Hayton, Ph.D.; David C. Pattison, M.D.; and Portia B. Watson, M.S. responsible for the increase of cardiovascular mortality. In a further review of the problem, Schroederl' proposed that the only state that could unfavorably affect all of the various conditions set forth was arterial hypertension. In addition, cadmium, which is found above allowable limits in tap water from soft water areas, can reproduce in rats the clinical and pathological picture of hypertensive disease, and should be carefully considered in attempting to solve the water factor. With all of the epidemiological data relating lipids to coronary heart disease, a logical question was whether or not men living in a hard water area have lower levels of serum lipids than their counterparts in a soft water area, particularly since the calcium content of the hard water consumed might make an important contribution to the overall calcium intake. With this in mind, a sampling study was done, choosing two hard water areas in different settings with varied social factors (Omaha, Nebraska, USA, and London, UK), and two soft water areas ( Salem, North Carolina, USA, and Glasgow, UK). This is a report of the findings from the four areas. Methods Since it is not possible to assign individuals to the areas planned for any survey, advantage must be taken of existing populations which are as similar as possible for other pertinent variables which might affect serum lipid or ion levels. The use of employees of companies having similar plants in hard and soft water areas offers obvious advantages both in study design of the experiment and in the mechanism of executing it, and this was done in this case. In Table I is shown the values of the chemical quality of the drinking water in the areas surveyed, Omaha, Salem, London and Glasgow. Some variation of SERUM PARAMETERS 169

2 these values exists within each area, but the variation is not significant in terms of the overall differences between the hard and the soft water areas. Also, Glasgow has about oneand-one-half times the cardiovascular mortality of London,5 and North Carolina about one-and-one-half times the cardiovascular mortality of Nebraska. Assuming a 5% difference in serum parameters, it was estimated that between 150 and 200 volunteers from each location would be sufficient to provide significantly different data in the four populations surveyed. In order to maintain comparability of the groups for such factors as age, sex, etc., only subjects between the ages of 30 and 50 who had worked and resided in the specific area for at least five years were accepted into the study. In the two groups from the United States, 200 men were selected in each location. The number of non-whites was approximately the same in each group. The response rate at both locations was over 95%, giving 196 men in Omaha (mean age 37 years) and 191 in Salem (mean age 38 years). Heights and weights were also similar. In the United Kingdom, a sample of 150 subjects (largely female to provide experience for this sex also) was selected from each area and all volunteers were Caucasian. The mean age in the London area was 41 years, with 85% being female, and in the Glasgow area 40 years with 86% being female. Once again heights and weights were similar. The response rate in the London area was 99%, giving 149 subjects, but in the Glasgow area it was only 71 %, giving 107 subjects. The higher drop-out rate after selection in Glasgow was apparently related to the somewhat longer delay in initiation of the study after selection of subjects and anxiety related to the bloodletting procedures. A review of the characteristics of the non-volunteer group showed no significant differences from those of the volunteers and in order not to add any selection bias to the study, all of the serum data from both areas was subsequently utilized. The subjects completed a history form which asked for information pertaining to diet, smoking habits, physical activity, use of a water softener, and medical history. They were brought to the medical departments where height and weight were measured and a fasting blood specimen drawn. The blood samples were immediately separated, frozen and stored until analyzed for serum total lipid, phospholipids, cholesterol, triglycerides, free fatty acids, and serum ions. Results Despite the fact that subjects had been drawn from similar industrial complexes in which the nature of the work was quite comparable, as were many of the other socioeconomic factors, and because serum lipids may be affected by so many factors, a review of some of the more important variables is in order, particularly since local cultural and environmental effects most certainly exist. Since much has been said about the noxious effects of smoking, the smoking patterns of the subjects were evaluated. Comparison of the smoking patterns in Salem and Omaha shows no significant difference; however in Glasgow there is a somewhat increased and heavier smoking pattern than in London, but the difference between the two locations is not significant and a comparison of all four areas shows only minor variation. (Table 2) Table 1-Chemical Characteristics of Water Supplies Total hardness, CaCO3, mg/liter Calcium, mg/liter Magnesium, mg/liter Copper, ug/liter N.D. N.D Zinc, ug/liter N.D Chromium N.D. N.D. N.D. N.D. Cobalt N.D. N.D. N.D. N.D. 'N.D. = Not detectable Table 2-Cigarette-Smoking Patterns No. % No. % No. % No. % Never smoked Quit Less than 1 pack/day pack/day or more packs/day Totals AJPH FEBRUARY, 1973 Vol. 63, No. 2

3 The amount of fat in the diet had to be estimated from a series of questions asking about average consumption of meat and dairy products. An experienced dietitian reviewed the questionnaires and assigned each subject an arbitrary value of low, medium or high fat intake. The results are presented in Table 3, and show a significantly higher (P<0.01) number of subjects with moderate fat intake in London than in Glasgow. Omaha volunteers showed a slightly greater proportion with high fat intake than Salem, but not significantly so. Acknowledging the limitations of such dietary histories, and realizing that the data may not reflect actual values, fatty acid analysis of the serum triglycerides was done to add some objectivity to the fat intake evaluation since the determined linoleate accurately reflects the dietary linoleate for the previous three weeks.12 These results are also presented in Table 3, and show a suggestively higher linoleate intake (.10> P >.05) in the London area (less saturated) as compared to Glasgow, but this is of course not statistically significant. However, comparing Salem to Omaha, there is a statistically significant (P<0.01) higher intake of linoleate in the former indicating higher polyunsaturated fat intake than in the beef center of Omaha. The use of vitamin and mineral supplements was quite uncommon and could not play any significant role in the results. Water softeners were not used in London; however the use of water softeners was much higher among the men in Omaha than in Salem. Thirty subjects in Omaha reported using such equipment for periods of one to eight years. Only two subjects in Salem used water softeners. The use of well water was much more common in Salem. Over 50% of the subjects there obtained their water from wells as compared to nine in Omaha. The chemical values of water in such wells, however, are similar to those of treated water and the differences between location are still maintained. Table 3-Estimated Fat in Diet No. % No. % No. % No. % Low Moderate High Totals Dietary linoleate percentage, Mean + S.D Table 4-Comparison of Serum Cholesterol, Triglycerides and Phospholipids Cholesterol, mg/100 ml 241 ± 46* 228 ± ± Triglycerides, mg/l100 ml ±-52 Phospholipids, mg/100 ml 212 ± ± ± *Mean + S.D. Table 5-Comparison of Serum Free Fatty Acids and Total Lipids Free fatty acids, meq/liter 765 ± 36* 751 ± ± ± 18 Total lipids, mg/100 ml 805 ± ± ± *Mean + S.D. SERUM PARAMETERS 171

4 A comparison of the serum cholesterol, triglycerides and phospholipids in the four cities is shown in Table 4. The mean serum cholesterol level for the London group is 6% higher than for the Glasgow group (P <0.05). Since no statistically significant difference in linoleate intake was noted between the two groups, no correlation between the cholesterol level and the type of fat ingested could be made. The mean serum cholesterol level for the Omaha group was approximately 5% greater than for the Salem group (P <0.05), and, as expected, correlated inversely to the linoleate intake of the two areas. The mean values for serum triglycerides are not significantly different when comparing Omaha to Salem, but the mean values for the serum triglycerides showed that the London group had a 14% higher level than the volunteers in Glasgow (P <0.05) with the difference being statistically significant. Although no determination was made, this may reflect a higher carbohydrate intake by the London group. The comparison between the locations for the phospholipids shows that there is a 10% lower mean value for the Omaha group than for Salem, P <0.05. However, when comparing the same parameter in London and Glasgow, it is found that the latter group had a non-significant 4 mg/100 mg higher level, making it difficult to evaluate the importance of the phospholipid in this survey. The serum free fatty acids and total serum lipid levels are presented in Table 5. In Omaha, the free fatty acids were slightly higher than in Salem, but not significantly so. The same situation occurred in the United Kingdom with somewhat higher levels in Glasgow than in London, but the significance was borderline and difficult to interpret. As regards the total serum lipids, the mean level was 24 mg/i00 ml higher in Omaha than in Salem and 30 mg/100 ml higher in Glasgow than in London. Neither comparison was significantly different statistically. The comparison of the serum calcium and magnesium results is presented in Table 6. The serum calcium is 8% higher (P<0.01) and the serum magnesium is 5% higher (P<0.01) in Omaha than in Salem. In London, the serum calcium level was slightly lower than in Glasgow, but the difference was not statistically significant. However, in regard to the serum magnesium levels, in London the mean was 16% higher and this was significant at the 99% level. The finding of the higher calcium levels in the United States and the higher magnesium levels in both hard water areas is surprising in view of the numerous previous reports of stability of the two parameters. In Table 7 is shown a comparison of serum copper, chromium, zinc and cobalt levels. This data was only available for the United Kingdom portion of the study. The serum copper was 72% higher (P<0.01), the serum chromium more than 100% higher (P<0.01), and the serum cobalt 48% higher (P <0.05) in the London group than in the volunteers from Glasgow. The serum zinc was also somewhat higher in London but the difference was small and insignificant. Discussion It had been hoped that completion of this survey in several parts of the world would clarify many questions that had been raised in regard to the nature of the "water factor," However, a number of not easily explained results were obtained. The serum cholesterol was higher in both hard water areas, and inversely related to reported cardiovascular mortality rates for the areas. The serum triglycerides were also elevated in Omaha and London when compared to their respective soft water counterparts, and also inversely related to cardiovascular mortality, both results being opposite to numerous surveys correlating these parameters directly. Also, the serum calcium levels were not different in London and Glasgow, a finding that did not support the higher level noted in Omaha as compared to Table 6-Comparison of Serum Calcium and Magnesium Calcium, mg/i 00 ml ±0.02* ± 0.09 Magnesium, meq/liter ± 0.03 'Mean + S.D. Table 7-Comparison of Serum Copper, Chromium, Zinc and Cobalt London Glasgow Copper, mg/liter * 1.15 ± 0.03 Chromium, mg/liter Zinc, mg/liter ± ± Cobalt, mg/liter *Mean ± S.D. 172 AJPH FEBRUARY, 1973 Vol. 63, No. 2

5 Salem. These findings may reflect the limited sample size, or possibly be a reflection of the presence of females in the United Kingdom portion of the study. In the case of the serum magnesium, however, the significantly higher level found in both the London and Omaha groups with the lower cardiovascular mortality rate suggests considerable importance for this parameter, and further detailed investigation of its potential importance appears to be in order. Goldsmith13 in an extensive review had suggested that higher serum magnesium levels were found in subjects with prolonged clotting times and might thus be related to blood coagulation and to the thrombotic process. The finding of the significantly higher mean serum copper, chromium and cobalt levels in London, while there were similar serum zinc levels in both London and Glasgow, is especially interesting, since the concentration of copper and zinc in the water supplies was identical in both areas. It suggests that in the case of copper, some concentration has occurred in the blood and that this ion may be of singular importance in protecting against cardiovascular disease. Of course, no detectable levels were available in this study for chromium and cobalt levels in the water supplies, and the possibility is raised that even in small concentrations these ions or some ions (either singly or in combination) not measured in blood or water may play a role of importance. It is obvious that more questions have been raised than have been answered by this survey. The accepted doctrines of (1) higher serum cholesterol and triglyceride levels being associated with higher area incidence of cardiovascular disease and (2) serum magnesium levels being stable appear to require further examination. Also the entire spectrum of trace metals which may be biologically important in the etiology of coronary heart disease has been largely overlooked to date and needs intensive careful epidemiological investigation. References 1. Kobayashi, J. Relationship between the chemical nature of river water and death rate from apoplexy. Ber. d. Ohara Inst. Land Biol. 11:12-21, Schroeder, H. A. Relationship between mortality from cardiovascular disease and treated water supplies. JAMA 172: , Morris, J. N.; Crawford, M. D.; and Heady, J. A. Hardness of local water supplies and mortality from cardiovascular disease in the county boroughs of England and Wales. Lancet 1: , Bi6rck, G.; Bostrom, H.; and Widstrom, A. On the relationship between water hardness and death rate in cardiovascular disease. Acta med. Scand. 178: , Crawford, T. and Crawford, M. D. Prevalence and pathological changes of ischemic heart disease in a hard water and in a soft water area. Lancet 1: , Robertson, J. S. Letter to Editor. Lancet 2: , Fleischman, A. I.; Yacowitz, H.; Hayton, T.; and Bierenbaum, M. L. Effects of dietary calcium upon lipid metabolism in mature male rats fed beef tallow. J. Nutr. 88: , Anderson, T. W.; le Riche, T. W.; and MacKay, J. S.; Sudden death and ischemic heart disease: correlation with hardness of local water supply. New Eng. J. Med. 280: , Rodstein, M.; Wolloch, L.; and Gubner, R. Prognostic significance of extra systoles in an insured population. Proceedings of Conference on CVD Epidemiology, March 1907, p Masironi, R. Trace elements and cardiovascular disease. Bull. Wld. Hlth. Org. 40: , Schroeder, H. A. Tne water factor. New Eng. J. Med. 280: , Holman, R. T.; Caster, W. O.; and Wiese, H. F. Estimation of linoleate intake of men from serum lipid analysis. Amer. J. Clin. Nutr. 14: , Goldsmith, N. F. and Goldsmith, J. R. Epidemiological aspects of magnesium and calcium metabolism Arch. Environ. Hlth. 12: , Dr. Bierenbaum, Dr. Fleischman, Dr. Hayton and Ms. Watson are affiliated with the Atherosclerosis Research Group, St. Vincent's Hospital, Montclair, New Jersey. Dr. Dunn is Staff Medical Director, Western Electric Company, New York. Dr. Pattison is Medical Adviser, Post Office, London EC4, England. This paper was submitted for publication in September, Reprint requests should be addressed to Dr. Bierenbaum, Atherosclerosis Research Group, 48 Plymouth St., Montclair, New Jersey. SERUM PARAMETERS 173