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(Hypertension. 1997;29:930-936.)
© 1997 American Heart Association, Inc.

Articles

Nutrient Intake and Blood Pressure in the Dietary Intervention Study in Children

Denise G. Simons-Morton; Sally A. Hunsberger; Linda Van Horn; Bruce A. Barton; Alan M. Robson; Robert P. McMahon; Linda E. Muhonen; Peter O. Kwiterovich; Norman L. Lasser; Sue Y. S. Kimm; ; Merwyn R. Greenlick

From the National Heart, Lung, and Blood Institute, Bethesda, Md. (D.G.S.-M.); Northwestern University Medical School, Chicago, Ill (L. Van H.); Maryland Medical Research Institute, Baltimore (B.A.B., R.P.M.); Children's Hospital, New Orleans, La (A.M.R.); University of Iowa, Iowa City (L.E.M.); Johns Hopkins University, Baltimore, Md (P.O.K.); New Jersey Medical School, Newark (N.L.L.); University of Pittsburgh (Pa) (S.Y.S.K.); and Kaiser Permanente Center for Health Research, Portland, Ore (M.R.G.).

	Abstract

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Abstract Delineating the role that diet plays in blood pressure levels in children is important for guiding dietary recommendations for the prevention of hypertension. The purpose of this study was to investigate relationships between dietary nutrients and blood pressure in children. Data were analyzed from 662 participants in the Dietary Intervention Study in Children who had elevated low-density lipoprotein cholesterol and were aged 8 to 11 years at baseline. Three 24-hour dietary recalls, systolic pressure, diastolic pressure, height, and weight were obtained at baseline, 1 year, and 3 years. Nutrients analyzed were the micronutrients calcium, magnesium, and potassium; the macronutrients protein, carbohydrates, total fat, saturated fat, polyunsaturated fat, and monounsaturated fat; dietary cholesterol; and total dietary fiber. Baseline and 3-year longitudinal relationships were examined through multivariate models on diastolic and systolic pressures separately, controlling for height, weight, sex, and total caloric intake. The following associations were found in longitudinal analyses: analyzing each nutrient separately, for systolic pressure, inverse associations with calcium (P<.05); magnesium, potassium, and protein (all P<.01); and fiber (P<.05), and direct associations with total fat and monounsaturated fat (both P<.05); for diastolic pressure, inverse associations with calcium (P<.01); magnesium and potassium (both P<.05); protein (P<.01); and carbohydrates and fiber (both P<.05), and direct associations with polyunsaturated fat (P<.01) and monounsaturated fat (P<.05). Analyzing all nutrients simultaneously, for systolic pressure, direct association with total fat (P<.01); for diastolic pressure, inverse associations with calcium (P<.01) and fiber (P<.05), and direct association with total and monounsaturated fats (both P<.05). Results from this sample of children with elevated low-density lipoprotein cholesterol indicate that dietary calcium, fiber, and fat may be important determinants of blood pressure level in children.

Key Words: children • diet • nutrition • trace elements • child nutrition • blood pressure

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Diet has been implicated as one of many factors that can influence BP,¹ which is an important risk factor for cardiovascular disease and stroke.² Identification of factors that may cause the age-related increase in BP seen in the US population³ may contribute to methods for the prevention of such increases. Factors related to BP in children may be particularly important in this regard because BP levels have been seen to track from childhood to adulthood.^{4 5 6}

The literature on the relationships between micronutrients and BP is controversial, and the literature on macronutrients and BP is sparse, particularly in children. Inverse associations with dietary calcium and SBP in children have been reported,⁷ as has significant lowering of BP by calcium supplements in adolescents and young adults.⁸ Inverse associations have been seen between dietary magnesium and DBP in boys⁹ and girls¹⁰ and between dietary potassium and SBP in children.¹¹ Studies in adults have reported inverse associations between BP and calcium^{12 13 14} and between BP and magnesium.^{15 16 17} Inverse associations between BP and potassium also have been seen in adults.^{12 13 18} Other studies, however, have not found significant effects of these micronutrients on BP in children^{19 20} or adults.^{21 22} Reviewers have concluded that the evidence of an effect of calcium on BP is not conclusive²³ or that the effect is small^{24 25} and that the relationship between magnesium and BP is controversial.²⁴ Although reviews have concluded that potassium has an inverse effect on BP,^{26 27} results from randomized trials have been inconsistent.^{15 28 29}

Few studies of the relationships between BP and dietary macronutrients, cholesterol, or fiber in children have been reported. One study of diet and BP in 9-year-old children found inverse relationships between DBP and fiber in boys and between SBP and protein, cholesterol, and fiber in girls²⁰ ; another study found an inverse association between fiber and DBP in girls.¹⁰ A review of studies of dietary fats and BP in adults found inconsistent results across studies, although some controlled trials have shown modest BP-lowering effects of diets higher in the ratio of polyunsaturated to saturated fat.³⁰ One report suggested an inverse association between protein and BP in adults.³¹ Some studies have found inverse associations between dietary fiber and DBP^{16 32} as well as between vegetable protein and the ratio of polyunsaturated to saturated fat and SBP.³¹ A recent review of 46 publications of studies examining dietary nutrients and BP in children concluded that there is a paucity of studies examining the effects of multiple nutrients and/or macronutrients in children.³³

The purpose of this article is to present analyses of relationships between dietary micronutrients and macronutrients and BP in children enrolled in DISC, a clinical trial of a dietary intervention to reduce elevated LDL-C. DISC obtained detailed information on dietary intake over 3 years and annual BP measurements and therefore provides a longitudinal data set that allows exploration of nutrient-BP relationships in children.

	Methods

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Participants
DISC is a collaborative, six-center, randomized controlled trial to test the efficacy and safety of dietary intervention for lowering elevated LDL-C in pubescent children. The study was approved by the Institutional Review Boards of all participating institutions. Parents or guardians of the participating children provided informed consent.

DISC eligibility criteria, baseline characteristics, study design, and intervention are described in detail elsewhere.^{34 35} In brief, the eligibility criteria for the DISC trial required LDL-C levels from the 80th to less than the 98th percentiles based on age-gender distributions from the Lipid Research Clinics.³⁶ Eligibility ages for boys were from 8 years, 7 months to 10 years, 10 months and for girls from 7 years, 10 months to 10 years, 1 month at the first screening visit. Because of sex differences in maturation rates, eligibility ages for boys were about 1 year older than for girls to maximize the likelihood that the participants would be studied during their most rapid growth period. No evidence of pubertal development could be present, based on Tanner stage (ie, Tanner stage 1).³⁷ The children were required to have no major illness and not be taking medications that might affect blood lipids or growth.

The BP exclusion criterion for the DISC trial was SBP of 125 mm Hg or greater or DBP (phase IV) of 80 mm Hg or greater documented at both the second screening and baseline visits. The purpose of the BP eligibility cut points was to exclude children with hypertension at baseline as defined by the Second Task Force on Blood Pressure Control in Children.³⁸

DISC participants were randomly assigned to receive the intervention (n=334) or usual care (n=329). The DISC intervention is described in detail elsewhere.³⁵ Briefly, the intervention consisted of individual, group, and family education and counseling to achieve dietary changes to reduce LDL-C. The DISC dietary goals were 28% of calories from total fat, 8% of calories from saturated fat, 9% of calories from polyunsaturated fat, and 75 mg/1000 kcal of cholesterol not to exceed 150 mg/d.

The results on change in LDL-C and growth after 3 years of intervention have been reported.³⁹ In summary, the DISC intervention achieved significant decreases in dietary total fat, saturated fat, and cholesterol levels (all P<.001) between the intervention and usual care groups. The net difference in LDL-C between the intervention and usual care groups at 3 years, adjusting for baseline LDL-C and sex, was -0.09 mmol/L (-3.3 mg/dL) (P=.02). There were no adverse effects on growth and development, including the primary safety outcomes of height and serum ferritin.

This report presents an analysis of data from all DISC participants who had data on BP, diet, and control variables for at least one of three measurement time points in the DISC trial: baseline, 1 year, and 3 years.

Data Collection and Measurements
The following measurements were taken at baseline, 1 year, and 3 years.

Dietary Intake
The DISC dietary assessment methods have been described in detail elsewhere and validated^{40 41} and are summarized here. Dietary intake data were collected by Nutrition Coordinating Center (NCC)–trained and certified dietitians blinded to the participant's group assignment. Three nonconsecutive 24-hour dietary recalls were collected at each time point using a standardized protocol, with the first recall collected face-to-face and the next two recalls collected by telephone. The three recalls were completed within 2 weeks of the measurement clinic visit and included 1 weekend day. The data collection interview method and nutrient coding were the same for all recalls. In a pilot study, there were no significant differences between in-person and telephone recalls.⁴¹

Dietitians interviewed the participant and obtained additional information from the parent as needed. The pilot study confirmed the children's ability to recall their own dietary intake instead of relying on parental or surrogate input.⁴¹ Three-dimensional food models for portion-size estimates were used for clinic-administered recalls, and two-dimensional models were used for telephone-administered recalls. Information on the use of dietary supplements also was obtained. The dietary recall records were mailed to the NCC in Minneapolis for centralized nutrient analysis. Study nutritionists compared nutrient results with the raw data from each recall to identify questionable values. Recalls with discrepancies were edited and reanalyzed by the NCC. Masked duplicate recalls were analyzed in 10% of the sample.

The three recalls at each time point were averaged to obtain the measures of nutrient intake at that time point. Micronutrients (calcium, magnesium, and potassium) and cholesterol were calculated as milligrams per day, and macronutrients (fat, protein, and carbohydrate) and fiber as grams per day. For the analyses in this article, total fat was obtained by adding the amounts of saturated, polyunsaturated, and monounsaturated fats.

Use of discretionary salt, high sodium seasonings, or low sodium food products was not determined. Urinary measures of micronutrient excretion were not obtained.

Blood Pressure
BP was measured with the method from the Program on the Epidemiology of Blood Pressure in Childhood, Youth, and Early Adulthood.⁴² Clinic staff were trained, certified, and recertified annually to follow the protocol for BP measurements. These staff were blinded to participant treatment assignment. DBP was measured by both Korotkoff phase IV and phase V. On the basis of recommendations for BP standards in children aged 3 to 12 years,³⁸ Korotkoff phase IV was used as the DBP measure in analyses. Two readings were taken with a Hawksley random-zero sphygmomanometer, and the average of the two readings was used after correction for the random zero. Routine reports on between-observer and within-observer differences, as well as on observer digit preference, were reviewed regularly by the DISC Quality Assurance Committee, and any problems in measurement were corrected by staff feedback and training.

Weight and Height
Clinic staff were specially trained in a common protocol for obtaining weight and height measurements, certified and recertified annually, and blinded to participant treatment assignment. Height was measured in centimeters with stadiometers constructed by the Medical Instruments Unit of the University of Iowa. Weight was measured in kilograms, and scales at all sites were calibrated weekly against a range of standard weights between 20 and 100 kg using a common protocol. Quality assurance reports on height and weight measurements were reviewed regularly, and corrective measures were taken as needed.

Statistical Methods
Of the total 663 DISC participants, 1 did not have all the data at any of the time points, leaving a sample size of 662 participants for analysis. Data from the intervention and usual care groups and from boys and girls were pooled because all nutrient–by–treatment group and nutrient-by-sex interactions were nonsignificant, indicating that the relationships between nutrients and BP were the same in both treatment groups and both sexes. Pooling the data from the groups provides a broader distribution of dietary nutrient intake and a larger sample size, which increases statistical power.

DBP and SBP were analyzed separately as dependent variables. Independent variables included dietary micronutrients (potassium, calcium, and magnesium), macronutrients (total fat, saturated fat, polyunsaturated fat, monounsaturated fat, carbohydrates, and protein), dietary cholesterol, and total dietary fiber. Because sodium intake was not adequately measured, it was not included in analyses.

Cross-sectional analyses, which allow one to examine associations between nutrients and BP at one point in time, were conducted at baseline by multiple linear regression. Longitudinal regression analyses over 3 years were conducted with a two-stage random effects model, which uses data from all time points on all variables and takes into account the correlation between measurements on the same person.⁴³ Longitudinal models allow one to utilize all data available, increase statistical power, and examine the independent effect of time.

Sex, height, and weight were used as control variables in all models because these were identified as potential confounders. At baseline, sex, height, and weight were all significantly correlated with both SBP and DBP (absolute value of r from .11 to .29, all P<.01) and also with all of the micronutrients and macronutrients of interest (absolute value of r from .11 to .27, all P<.01), except the correlation between calcium and weight, which was not significant. When correlations of body mass index (weight over height squared) with nutrients were examined, most were not significant, so controlling for height and weight separately, rather than using the composite body mass index measure, was determined to provide better control for confounding. Since the age range of participants was narrow (8 to 11 years old at baseline), age was not included as a control variable.

All analyses also were adjusted for total caloric intake. For the micronutrient, fiber, and cholesterol analyses (ie, nutrients that do not contain calories), total kilocalories was included as a separate control variable. For macronutrient analyses (ie, nutrients that provide calories), total kilocalories was controlled for by creating the variable "other kilocalories," which equaled total kilocalories minus the kilocalories from the macronutrient of interest, or in the multivariate models by including all sources of calories in the models. Total kilocalories was included as a separate variable, or all sources of calories were included, rather than using nutrient density measures (eg, milligrams per 1000 kcal or percentage of calories) because this method allows us to look at the specific effects of each nutrient on BP while controlling for total calories.^{44 45} Nutrient density measures do not allow us to separate the effect of the nutrient and the effect of the total calories because both are contained together in the same independent variable. The ratio of polyunsaturated to saturated fat was not used in modeling because it was of interest to consider the effects of each nutrient individually. If there is no interaction between polyunsaturated and saturated fat, the final model can provide information about the ratio, and the ratio is of interest only if either of the nutrients is statistically significant.

We used cross-sectional baseline analyses and 3-year longitudinal analyses to examine the relationships of each nutrient separately with SBP and DBP. In addition, we conducted 3-year longitudinal analyses with all nutrients included as independent variables to determine the independent effect of each nutrient, while controlling for all other nutrients. We conducted one such analysis using total fat and a separate analysis using the components of total fat, ie, saturated, polyunsaturated, and monounsaturated fats.

After the mean value of height and weight was subtracted from each individual's height and weight, there was no significant collinearity between variables in any of the multivariate models, including collinearity of the nutrients with each other.

Additional analyses retained the randomization assignments and compared the intervention and usual care groups as to the effects of the DISC dietary intervention on SBP and DBP levels. ANCOVA models⁴⁶ were used to test the effect of intervention on SBP and DBP separately at 3 years, with baseline value of BP and sex as covariates.

Because DISC was not specifically designed to answer research questions about diet and BP, the analyses for this report are viewed as exploratory. No adjustments are made for multiple comparisons.

	Results

Top Abstract Introduction Methods Results Discussion References

 
The characteristics of participants at baseline, including BP and dietary intake, are shown in Table 1. Dietary intake data were available for 653 (98.6%) of participants at the baseline visit. The nutrient intakes in this cohort were similar to intakes reported by 6 to 11 year olds in the National Health and Nutrition Examination Survey (NHANES) III, non-Hispanic white population,⁴⁷ although the intake of total fat was lower in the DISC sample. Data derived from eight studies of healthy children in the United States show slightly higher mean age-specific BP values⁴⁸ than in the DISC cohort; this is not unexpected because the BP eligibility criteria for the DISC trial excluded children with high BP levels.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Subjects at Baseline, Including Blood Pressure and Dietary Intake: Dietary Intervention Study in Children

Analyses examining each nutrient separately are shown in Table 2. Cross-sectional analyses at baseline showed potassium significantly inversely associated with SBP (P<.01). In 3-year longitudinal analyses, there were significant inverse associations between SBP and calcium (P<.05), magnesium (P<.01), potassium (P<.01), protein (P<.01), and fiber (P<.05), and there were significant positive associations with total and monounsaturated fats (both P<.05). For DBP cross-sectionally at baseline, calcium (P<.05), magnesium (P<.05), potassium (P<.01), and fiber (P<.01) were significantly inversely associated with DBP. Three-year longitudinal analyses showed significant inverse associations between DBP and calcium (P<.01), magnesium (P<.05), potassium (P<.05), protein (P<.01), carbohydrates (P<.05), and fiber (P<.05) and significant positive associations with polyunsaturated and monounsaturated fats (both P<.01).

View this table: [in this window] [in a new window]   Table 2. Relationships Between Dietary Nutrients and Blood Pressure (Each Nutrient Analyzed Separately)

Analyses with all nutrients included as independent variables are shown in Table 3. For SBP, in the multivariate longitudinal model that included all nutrients and total fat, only total fat was significantly directly associated with SBP (P<.01). In the multivariate longitudinal model that included the components of total fat (saturated, polyunsaturated, and monounsaturated fats), there were no significant associations between nutrients and SBP. For DBP, in the longitudinal model including all nutrients and total fat, total fat was significantly positively associated with DBP (P<.05), and calcium (P<.01) and fiber (P<.05) were significantly inversely associated with DBP. In the longitudinal model with all nutrients and the components of total fat, calcium and fiber were significantly inversely associated with DBP (both P<.05), and monounsaturated fat was significantly directly associated with DBP (P<.05).

View this table: [in this window] [in a new window]   Table 3. Relationships Between Dietary Nutrients and Blood Pressure (All Nutrients Analyzed Simultaneously)

Time (measured by months from baseline) was not statistically significant in any of the longitudinal models after controlling for height and weight. Height was not significant in any models of SBP but was significant in all the models of DBP (ß coefficients ranging from .10 to .27, all P<.05).

As reported previously, the DISC intervention and usual care groups were comparable in characteristics at baseline, and the DISC intervention achieved significantly greater decreases in dietary total fat, saturated fat, and cholesterol levels (all P<.001) in the intervention group compared with the usual care group.³⁹ Approximately 88% of participants had 3-year BP measurements. The effects of the intervention on SBP and DBP at 1 and 3 years are shown in Table 4. The change in BP from baseline was not significantly different in the intervention group than the usual care group, although all point estimates of effect indicated a greater decrease in BP in the intervention group than the usual care group. Treatment-by-time interaction terms in the multivariate models that included all nutrients also were not significant; this result also indicates that the DISC dietary intervention did not significantly lower BP in the intervention children compared with usual care children, even while controlling for all nutrients, height, weight, and sex.

View this table: [in this window] [in a new window]   Table 4. Blood Pressure Outcomes by Treatment Group

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study examined relationships between dietary nutrients and BP in growing pubescent children while controlling for sex, height, weight, and total caloric intake. The strengths of this study include the following: (1) multiple dietary recalls at each time point that allow for more accurate measurement of diet than a single recall, (2) analysis of dietary recalls through a nutrient database that included both micronutrients and macronutrients, (3) careful BP measurement with quality control, (4) data collected over 3 years that allow for longitudinal data analysis, and (5) data on major factors, such as height, that affect BP and are correlated with dietary intake and so should be controlled for in analyses. Updated normative BP tables for children and adolescents are based on height percentiles because of the importance of height in determining BP levels in children.⁴⁹ Limitations of the study include inadequate measurement of salt intake (which limited our ability to study effects of sodium on BP or to control for effects of sodium on the relationships between other nutrients and BP), exclusion of children with high BP at baseline (which truncates the BP distribution), and use of a sample that was neither a random population sample nor based on nutrient-BP hypotheses. The findings are best viewed as indicators of potentially important dietary components that warrant further study.

The DISC participants all had elevated LDL-C and so were not representative of the general population of children. In this report, total fat intake was defined as the sum of saturated, polyunsaturated, and monounsaturated fatty acids. The main analysis of DISC participants' intake at baseline, which determined total fat directly, found means of 33.4% and 34.0% of calories from fat in intervention and usual care participants,³⁹ which are similar to those found in NHANES III for 1988-1991.⁴⁷

The analyses of individual nutrients in the current study found inverse associations between calcium, magnesium, and potassium and both SBP and DBP. These findings are consistent with some other studies that have found inverse relationships between the three micronutrients and BP in children.^{7 8 9 10 11} The findings of other studies, however, have not been consistent.^{19 20} A recent review located 9 studies of calcium and BP, 5 studies of magnesium, and 15 studies of potassium in children and adolescents.³³ Several of the prior studies did not control for important correlates of BP, such as height; the studies that did were more likely to find significant nutrient-BP relationships. Most prior studies did not control for multiple other nutrients. In single-nutrient analyses, effects on BP from other nutrients are not taken into account, which prevents one from determining the independent effects of each nutrient. When we controlled for all nutrients, including macronutrients, the only micronutrient that remained significant was calcium inversely associated with DBP.

Controlling for all nutrients, total fat was significantly directly associated with both SBP and DBP, and fiber was significantly inversely associated with DBP. These results provide evidence of a potential role of dietary fat, and possibly fiber, on BP levels in children. Our analyses comparing the intervention group with the usual care group, however, did not find a significant decrease in BP despite a significant decrease in dietary fat, saturated fat, and cholesterol in the intervention group, although the direction of effect was consistent with an inverse association. Only nine previous studies of the relationships between BP and dietary macronutrients in children have been reported, with inconclusive findings.³³ Our findings that total fat was directly associated with both DBP and SBP, and that total fiber was inversely associated with DBP, warrant further study. When we analyzed the components of total fat separately, we found that monounsaturated fat was directly associated with DBP level; this observation was unexpected and deserves further study. We did not find any independent effects of saturated or polyunsaturated fat on either SBP or DBP, but the estimated effect for monounsaturated fat on DBP is not large enough to account for the BP effect estimated for total fat.

The magnitude of the effects of nutrients on BP in this study, although statistically significant, was small. We estimated the magnitude of effect on BP using the regression coefficients that were significant in the longitudinal analyses (from Table 2) and assuming nutrient changes equivalent to 1 SD based on baseline data (shown in Table 1), with other factors held constant except for total calories, which was allowed to vary with macronutrient changes. The greatest effects of any single nutrient would be from magnesium or calcium: For magnesium, an increased intake of 65 mg/d would be associated with a 0.91–mm Hg lower SBP and 0.72–mm Hg lower DBP; for calcium, an increased intake of 331 mg/d would be associated with a 0.93–mm Hg lower DBP and 0.50–mm Hg lower SBP. Diets, however, are made up of multiple nutrients, and one needs to take into account combinations of nutrients to estimate the effects of dietary patterns. Using the results from the analyses that controlled for all nutrients simultaneously (Table 3), one can see that a decrease of approximately 2.5 mm Hg in DBP would occur if there were increases of 1 SD in both calcium and fiber and a decrease of 1 SD in total fat or monounsaturated fat. The estimated effect on SBP of a decrease of 1 SD in total fat from the multiple-nutrient model would be -0.76 mm Hg.

Although the results from this study have limited generalizability because of the select nature of the study population, it is useful to put the magnitude of BP effect into a broader context. On the basis of data from large, population-based observational studies in adults, it has been estimated that a downward shift in the population distribution of SBP of 2 mm Hg in adults would save about 12 000 lives per year in the United States.⁵⁰ The Hypertension Detection and Follow-up Program found that lowering DBP by only 4 mm Hg caused a marked reduction in all-cause mortality in adults.⁵¹ Additional research into dietary factors associated with BP should help refine the current recommendations for primary prevention of hypertension and BP control, which include decreasing sodium intake, increasing potassium intake, limiting alcohol consumption, and increasing aerobic exercise.^{2 52} Identifying determinants of BP in children is of primary importance in the prevention of hypertension.

	Selected Abbreviations and Acronyms

 

BP = blood pressure DBP = diastolic blood pressure DISC = Dietary Intervention Study in Children LDL-C = low-density lipoprotein cholesterol SBP = systolic blood pressure

	Acknowledgments

 
The DISC study is supported by cooperative agreements U01-HL-37947, U01-HL-37948, U01-HL-37954, U01-HL-37962, U01-HL-37966, U01-HL-37975, and U01-HL-38119 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. The authors would like to thank Dr Eva Obarzanek for providing consultation on this article.

	Footnotes

 
Reprint requests to Denise G. Simons-Morton, MD, PhD, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, II Rockledge Centre, MSC 7936, 6701 Rockledge Dr, Bethesda, MD 20892-7936.

Received June 10, 1996; first decision July 12, 1996; accepted October 31, 1996.

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