American Journal of Therapeutics 0, 1–6 (2015)

Raw Water Consumption Does Not Affect All-Cause or Cardiovascular Mortality: A Secondary Analysis Rohit S. Loomba, MD,1* Saurabh Aggarwal, MD,2 and Rohit R. Arora, MD2

Previous studies have examined water quality and its association with all-cause and cardiovascular mortality. However, there is a lack of data regarding association between the amount of water consumption and risk of mortality. We used the third National Health and Nutrition Examination Survey (NHANES III) database and its subsequent follow-up data. Only patients older than 45 years who reported amount of average water consumption and for whom follow-up mortality data were available were included in the study. Patients were stratified into following groups of average daily raw water consumption: (1) no water consumption, (2) #2 cups, (3) .2 to # 4 cups, (4) .4 to #6 cups, (5) .6 to #8 cups, and (6) $8 cups. End points studied were all-cause mortality, ischemia-related mortality, congestive heart failure–related mortality, and stroke-related mortality. Baseline characteristics were compared using t tests and Mann–Whitney U tests. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis using .6 cups to #8 cups of water a day group as reference. Multivariate analysis was then performed adjusting for various factors. P values of less than 0.05 were considered statistically significant. A total of 7666 patients were ultimately included in the study. Multivariate analysis demonstrated no significant differences in all-cause, ischemia-related, heart failure–related, or stroke-related mortality among various raw water intake groups when compared with the reference group. The significance noted for all-cause mortality in .2 glasses to #4 glasses a day group in the univariate analysis was not seen with multivariate analysis (odds ratio: 0.747; 95% confidence interval: 0.437–1.276; P 5 0.285). Daily raw water consumption does not seem to impact all-cause mortality or cause-specific cardiovascular mortality. Keywords: water, consumption, myocardial infarction, stroke, congestive heart failure, mortality, death

INTRODUCTION An association between water quality and mortality has been proposed since the 1950s, when Kobayashi1 demonstrated that increased water acidity in parts of Japan

1

Division of Cardiology, Children’s Hospital of Wisconsin/Medical College of Wisconsin Affiliated Hospitals, Wauwatosa, WI; and 2 Division of Medicine, Chicago Medical School, North Chicago, IL. The authors have no conflicts of interest to declare. All the authors listed have contributed to this article and are aware of its submission. *Address for correspondence: Children’s Hospital of Wisconsin/ Medical College of Wisconsin Affiliated Hospitals, 9000 Wisconsin Avenue, Wauwatosa, WI 53226. E-mail: [email protected]

was associated with increased mortality. Subsequent studies further explored the association between water quality and mortality. Nearly, 60 studies were conducted with various study data being pooled in several large reviews.2–6 After pooling individual study data, it was noted that water hardness was inversely associated with cardiovascular mortality, with harder water being associated with lower cardiovascular mortality. These findings, however, demonstrated variability in significance when various epidemiologic characteristics were altered between studies. Although many of the water quality studies did demonstrate a significant inverse relationship, significance was often noted only in subsets of the study population such as a particular gender. Some of these early studies also acknowledge that significance of association was lost as study populations were

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expanded to a larger geographic area. Additionally, inconsistencies in associations were noted even at the city level, leading Sharrett4 to conclude that individual cities may not represent independent sample units since they represent data from a geographically clustered area that is bound to have an element of homogeneity. Although this initial work focused on water hardness, little has been done to delineate the effect of the amount of water consumed on all-cause and cardiovascular-related mortality. The objective of this study is to determine whether the amount of raw water consumed per day impacts mortality.

METHODS The National Health and Nutrition Examination Survey (NHANES) is a national effort aimed at assessing the health and nutrition status of children and adults in the United States, with the patient population being representative of the US population. The NHANES database consists of demographic information as well as information drawn from questionnaires, physical examination, and laboratory testing. There are several iterations of NHANES, which have been assembled during various years. For this study, data from NHANES III were used, which consists of data regarding 33,994 patients collected from 1988 to 1994. This specific iteration of NHANES was selected as it was the most recent data set that also included linked mortality data. Mortality data were collected on patients included in NHANES III through December 31, 2006 and includes mortality status as well as cause of mortality among other parameters. Specifics regarding the design and implementation of the questionnaires used to collect the data in NHANES can be found in previous publications that have described the logistical aspects of the NHANES database. The NHANES database was reviewed and approved from the institutional review board, and written consent was obtained from participants. Patients older than 45 years were identified in the NHANES III database. Only patients with a response to the following questionnaire item were eligible for inclusion: “How much plain drinking water do you usually drink in a 24-hour period?” Those with no mortality data available were excluded. Included patients were stratified into the following groups of average daily raw water consumption: (1) no water consumption, (2) #2 cups, (3) .2 to #4 cups, (4) .4 to #6 cups, (5) .6 to #8 cups, and (6) $ 8 cups. American Journal of Therapeutics (2015) 0(0)

Loomba et al

Baseline characteristics were then compared for included patients between the various water intake groups using x2 analysis, t tests, and Mann–Whitney U tests. Next, odds ratios with 95% confidence intervals and P values were calculated to compare the prevalence of all-cause mortality, ischemiarelated mortality, congestive heart failure–related mortality, and stroke-related mortality. After this univariate analysis, a multivariate analysis was done to adjust for the following covariates: race, gender, total cholesterol, low-density lipoprotein levels, and highdensity lipoprotein levels. These specific covariates were selected as per the Framingham criteria. The .6 to #8 cups of free water intake group was used as the reference group for the univariate and multivariate analysis. All statistical analyses were performed using SPSS statistical software version 20.0 (Chicago, IL). A P value of less than 0.05 was considered statistically significant. A power analysis was also conducted.

RESULTS In this study, 7666 patients were ultimately included to analyze the effect of daily free water intake on mortality. Baseline characteristics demonstrated statistically significant differences in the number of males, age at initial screening, and body mass index between the various groups (Table 1). Univariate analysis did not demonstrate any significant differences in all-cause, ischemia-related, heart failure–related, or stroke-related mortality among various raw water intake groups when compared with the reference group. The exception to this, however, was with all-cause mortality and the group having reported more than 2 cups of water a day to less than or equal to 4 cups a day, which demonstrated an odds ratio of 1.221 (95% confidence interval: 1.045–1.427; P 5 0.012) (Table 2). Multivariate analysis with adjustments made for race, gender, total cholesterol, low-density lipoprotein levels, and high-density lipoprotein levels demonstrated no significant differences in all-cause, ischemia-related, heart failure–related, or strokerelated mortality among various raw water intake groups when compared with the reference group. The significance noted for all-cause mortality in the more than 2 glasses to 4 glasses a day group in the univariate analysis did not persist with multivariate analysis, which demonstrated an odds ratio of 0.747 (95% confidence interval: 0.437–1.276; P 5 0.285). www.americantherapeutics.com

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0.054 0.089 0.071 0.001 0.647 141.0 38.5 16.5 5.8 22.5 6 6 6 6 6 127.8 37.8 16.5 5.8 23.6 164.2 133.3 50.9 27.8 135.3 6 6 6 6 6

114.2 38.1 16.9 5.1 23.4

DISCUSSION

LDL, low-density lipoprotein; HDL, high-density lipoprotein; BMI, body mass index.

163.9 139.5 51.3 27.5 137.4 114.5 41.3 16.7 5.3.8 21.9 6 6 6 6 6 160.1 138.4 52.0 27.0 137.3 138.4 38.8 16.0 4.9 23.1 6 6 6 6 6 164.5 141.6 49.5 27.0 135.1

114.0 40.1 15.0 5.4 22.0

159.1 140.0 51.4 26.6 136.5 6 6 6 6 6

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Power analysis was conducted to determine the power of analysis between the defined groups and the reference group. Pearson correlation statistics of 0.5 and 0.6 were assumed for the experimental and reference groups, respectively, and a static sample size of 1001 for the reference group. It was determined that 370 patients in the experimental group would allow for a power of 90% in detecting a statistically significant difference with a P value of 0.05. For this study, the smallest group (those who reported a daily average of no raw water consumption) had 465 patients, which results in 94% power of this analysis detecting a statistically significant difference.

173.5 138.8 50.8 28.6 136.8 6 6 6 6 6

0.180 222.7 6 47.3 219.5 6 43.2 219.8 6 44.7

219.8 6 44.8

222.5 6 45.3

219.4 6 43.9

0.001 63.2 6 11.1 65.0 6 12.3 64.4 6 12.7

66.2 6 12.1

65.7 6 11.9

64.9 6 11.6

0.001 1329 627 (47.2) 1001 498 (49.8) 1677 779 (46.5) 1756 848 (48.3) 1438 673 (46.8) 465 240 (51.6)

N No. males, n (%) Age at initial screening Total cholesterol Triglycerides LDL HDL BMI Systolic blood pressure

More than 0 glasses to More than 2 glasses More than 4 glasses More than 6 glasses 2 glasses a day to 4 glasses a day a day to 6 glasses a day a day to 8 glasses a day No water a day

Table 1. Baseline characteristics.

More than 8 glasses a day

P

Lack of Association Between Water Consumption and Mortality

Findings from this study demonstrate that amount of water consumption does not affect all-cause, ischemiarelated, heart failure–related, or stroke-related mortality. Chan et al studied the association between fluid intake and coronary artery disease in an Adventist population. This study looked at fluid intake separated into water only and all other fluids. In respect to water, a significant negative association was noted between water intake and risk of coronary artery disease. Those who drank 5 or more glasses of water a day had lower risk of coronary artery disease. In respect to intake of fluids other than water, a significant positive association was noted. Men who drank 5 or more glasses of water a day compared with those who drank 2 or less glasses of water a day had a relative risk of 0.46 for fatal coronary heart disease. For women, the relative risk when comparing the same water intake levels was 0.59.7 Water hardness, specifically magnesium and calcium content, was the initial mechanism investigated by water quality studies. Magnesium is believed to be protective against acute myocardial infarction, as it helps to prevent the progression of atherosclerosis, aggregation of platelets, and calcification of soft tissue.8,9 Postmortem comparison of myocardial tissue demonstrates lower magnesium levels in those who died from cardiac causes when compared with myocardial tissue from those who died of noncardiac causes.10,11 Although these mechanisms account for associations between water quality and cardiovascular mortality, they do not account for possible associations between amount of water consumption and cardiovascular mortality. Increased water intake can help to regulate whole-blood viscosity, plasma viscosity, and hematocrit, all of which have been shown to alter risk of coronary artery disease and stroke.12–16 American Journal of Therapeutics (2015) 0(0)

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No water a day

More than 0 glasses to 2 glasses a day

More than 2 glasses to 4 glasses a day

More than 4 glasses a day to 6 glasses a day

More than 6 glasses a day to 8 glasses a day

More than 8 glasses a day

465

1438

1756

1677

1001

1329

1.006 (0.806–1.256)

0.992 (0.843–1.167)

1.221 (1.045–1.427)

1.115 (0.952–1.304)

Reference

0.974 (0.826–1.149)

0.954 1.927 (0.801–4.630)

0.923 1.437 (0.828–2.494)

0.012* 0.747 (0.437–1.276)

0.176 1.269 –(0.742– 2.174)

Reference Reference

0.759 1.221 (0.719–2.07)

0.143

0.198

0.285

0.384

Reference

0.460

0.749 (0.524–1.07)

0.830 (0.647–1.06)

1.022 (0.811–1.29)

0.971 (0.767–1.22)

Reference

0.933 (0.728–1.19)

0.112 2.793 (0.795–9.80)

0.142 1.805 (0.924–3.52)

0.849 1.414 (0.764–2.62)

0.807 1.739 (0.892–3.39)

Reference Reference

0.587 1.009 (0.523–1.94)

0.109

0.084

0.270

0.104

Reference

0.979

1.515 (0.573–4)

1.399 (0.651–3.00)

1.779 (0.870–3.65)

1.499 (0.717–3.13)

Reference

1.745 (0.827–3.68)

0.403 —

0.390 1.934 (0.221–16.94)

0.115 1.115 (0.162–7.69)

0.282 0.956 (0.157–5.84)

Reference Reference

0.144 0.334 (0.046–2.42)



0.552

0.912

0.961

Reference

0.278

1.319 (0.776–2.24)

0.856 (0.554–1.32)

0.959 (0.637–1.44)

1.038 (0.691–1.56)

Reference

0.685 (0.416–1.06)

(Continued on next page)

Loomba et al

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N All-cause mortality Unadjusted odds ratio and 95% confidence interval Unadjusted P Adjusted odds ratio and 95% confidence interval Adjusted P Ischemia-related mortality Unadjusted odds ratio and 95% confidence interval Unadjusted P Adjusted odds ratio and 95% confidence interval Adjusted P CHF-related mortality Unadjusted odds ratio and 95% confidence interval Unadjusted P Adjusted odds ratio and 95% confidence interval Adjusted P Cerebrovascular accident–associated mortality Unadjusted odds ratio and 95% confidence interval

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Table 2. Average water consumption and odds ratio.

More than 8 glasses a day

0.089 1.761 (0.424–7.322)

0.436

More than 6 glasses a day to 8 glasses a day

Reference Reference

Reference

More than 4 glasses a day to 6 glasses a day

0.857 0.690 (0.224–2.12)

More than 2 glasses to 4 glasses a day

0.839 0.747 (0.243–2.30)

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Strengths of this study include use of a large nationally representative patient population. The patients included in this sample also exhibit geographic diversity within the United States, overcoming a limitation noted earlier in regards to previous water studies. A limitation of this study is the lack of data on water quality. This study also possesses limitations inherent to those of similarly designed studies, which include the difficulty in determining a causal relationship, particularly because of the difficulty in which to determine the homogeneity of the ecologic effect on the study population.

CONCLUSIONS 0.518

Amount of free water consumption did not affect allcause, ischemia-related, heart failure–related, or stroke-related mortality.

0.775 0.692

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* Significant P value. CHF, congestive heart failure.

0.485 1.206 (0.334–4.34) 0.306 0.719 (0.141–3.67)

0.612

REFERENCES

Unadjusted P Adjusted odds ratio and 95% confidence interval Adjusted P

No water a day

More than 0 glasses to 2 glasses a day

Table 2. (Continued) Average water consumption and odds ratio.

Lack of Association Between Water Consumption and Mortality

1. Kobayashi J. Geographical relationship between the chemical nature of river water and death-rate from apoplexy. Berichte d ohara inst f landwirtsch Biologie. 1957;11: 12–21. 2. Neri LC, Hewitt D, Schreiber GB. Can epidemiology elucidate the water story? Am J Epidemiol. 1974;99:75–88. 3. Neri LC, Mandel JS, Hewitt D. Relation between mortality and water hardness in Canada. Lancet. 1972;1: 931–934. 4. Sharrett AR. The role of chemical constituents of drinking water in cardiovascular diseases. Am J Epidemiol. 1979;110:401–419. 5. Sharrett AR, Feinleib M. Water constituents and trace elements in relation to cardiovascular diseases. Prev Med. 1975;4:20–36. 6. Comstock GW. Water hardness and cardiovascular diseases. Am J Epidemiol. 1979;110:375–400. 7. Chan J, Knutsen SF, Blix GG, et al. Water, other fluids, and fatal coronary heart disease: the Adventist Health Study. Am J Epidemiol. 2002;155:827–833. 8. Durlach J, Bara M, Guiet-Bara A. Magnesium level in drinking water and cardiovascular risk factor: a hypothesis. Magnesium. 1985;4:5–15. 9. Eisenberg MJ. Magnesium deficiency and sudden death. Am Heart J. 1992;124:544–549. 10. Chipperfield B, Chipperfield JR. Heart-muscle magnesium, potassium, and zinc concentrations after sudden death from heart-disease. Lancet. 1973;2:293–296. 11. Chipperfield B, Chipperfield JR, Behr G, et al. Magnesium and potassium content of normal heart muscle in areas of hard and soft water. Lancet. 1976;1:121–122. 12. Becker RC. The role of blood viscosity in the development and progression of coronary artery disease. Cleve Clin J Med. 1993;60:353–358. American Journal of Therapeutics (2015) 0(0)

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6 13. Lowe GD, Lee AJ, Rumley A, et al. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol. 1997;96:168–173. 14. Lee AJ, Mowbray PI, Lowe GD, et al. Blood viscosity and elevated carotid intima-media thickness in men and women: the Edinburgh Artery Study. Circulation. 1998;97:1467–1473.

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Loomba et al 15. Koenig W, Ernst E. The possible role of hemorheology in atherothrombogenesis. Atherosclerosis. 1992;94:93–107. 16. de Simone G, Devereux RB, Chien S, et al. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation. 1990;81:107–117.

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Raw Water Consumption Does Not Affect All-Cause or Cardiovascular Mortality: A Secondary Analysis.

Previous studies have examined water quality and its association with all-cause and cardiovascular mortality. However, there is a lack of data regardi...
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