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Serum Uric Acid and Blood Pressure in Children atCardiovascular Risk

WHAT’ S KNOWN ON THIS SUBJECT: Uric acid (UA) is associatedwith hypertension in children, after body weight adjustment.

Whether the whole spectrum of variables, such as visceraladiposity, insulin resistance, puberty, and renal function,in uence the relationship between UA and blood pressure isunknown.

WHAT THIS STUDY ADDS: In a cohort of children at relatively highcardiovascular risk, the association between UA and bloodpressure levels is independent of several well-known factorsimplicated in the development of hypertension, such as insulinresistance, pubertal status, and renal function.

abstractOBJECTIVES: Hyperuricemia has been shown to be a strong correlateof hypertension in children. However, the complex interaction betweenserum uric acid (UA), systemic blood pressure (BP), and possiblyconfounding factors has been elucidated only in part.

METHODS: We evaluated of ce BP as well as clinical and biohumoralparameters in a cross-sectional cohort of 501 children (280 boys and221 girls) aged between 6 and 18 years (mean = 10.8 years)consecutively referred for cardiovascular risk assessment.

RESULTS: Overall, 156 (31.1%) were normotensive, 122 (24.4%) showed transient hypertension, 87 (17.4%) had prehypertension, and 136(27.1%) had hypertension. Altogether 33.3% and 40.5% of the studygroup were overweight or obese, respectively. There was a trend to-ward greater weight and waist circumference and higher BMI, Homeo-stasis Model Assessment index, and UA levels as the BP categoriesrose. Moreover, the prevalence of pubertal children, obesity, andwaist-to-height ratio above 0.50 progressively increased from lower to upper BP categories. After adjusting for puberty, gender, BMI(z -score), Homeostasis Model Assessment index, and renal function,UA was found to be directly related to systolic and diastolic BP values(P = .03). Using normotensive children for comparison, the risk of showing prehypertension or hypertension increased by at least 50%for each 1 mg/dL UA increase ( P , .01), whereas it doubled forchildren in the top gender-speci c UA quartile (P , .03).

CONCLUSIONS: Increased UA levels showed an independent predictivepower for the presence of higher BP levels among a cohort of childrenat relatively high cardiovascular risk. Pediatrics 2013;132:e93– e99

AUTHORS: Francesca Viazzi, MD,a

Laura Antolini, PhD,b ,c

Marco Giussani, MD,d Paolo Brambilla, MD,d Sara Galbiati,MD,b Silvana Mastriani, MD, e Andrea Stella, MD,b RobertoPontremoli, PhD, a Maria Grazia Valsecchi, PhD, b ,c andSimonetta Genovesi, MD b ,e

a University of Genoa and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la ricerca sul Cancro,Genova, Italy; b Department of Health Science, and c Center of Biostatistics for Clinical Epidemiology, University of Milano- Bicocca, Monza, Italy; d Family Pediatrician, Milano, Italy; and e Nephrology Unit, San Gerardo Hospital, Monza, Italy

KEY WORDSuric acid, children, hypertension, pre-hypertension, HOMA index,obesity

ABBREVIATIONSBP— blood pressureCI— con dence intervalCV— cardiovascularDBP— diastolic BPeGFR— estimated glomerular ltration rateHOMA— Homeostasis Model AssessmentHT— hypertensiveNT— normotensiveNW— normal weightOB— obeseOR— odds ratioOW— overweightPH— prehypertensive

SBP—

systolic BPTH— transiently elevated blood pressureUA— uric acidWtHr— waist-to-height ratio

Drs Viazzi and Genovesi conceptualized and designed the study,carried out the initial analyses, and drafted the initialmanuscript; Drs Antolini, Galbiati, and Valsecchi contributed toanalysis and interpretation of data, and reviewed themanuscript; Dr Giussani designed the data collectioninstruments, coordinated and supervised data collection, andcritically reviewed the manuscript; Dr Mastriani gavea substantial contribution to acquisition of data and revised thearticle critically; Drs Brambilla, Stella, and Pontremolicontributed to interpretation of data and critically reviewed the

manuscript; and all authors approved the

nal manuscript assubmitted.

(Continued on last page)

PEDIATRICS Volume 132, Number 1, July 2013 e93

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to measureplasma glucoseand insulin,and serum UA, total cholesterol, tri-glycerides, andhigh-densitylipoproteinconcentrations. Plasma glucose wasmeasured by a glucose oxidase methodand insulin was evaluated by chemilu-

minescent immunometric assay. Ho-meostasis Model Assessment (HOMA)index was calculated by dividing theproduct of plasma insulin ( mU/mL) andplasma glucose (mmol/L) by 22.5. 24

Glomerular ltration rate was esti-mated (eGFR) by means of the updatedSchwartz formula using serum creati-nine and height measurements and a k constant of 0.413. 25 Serum creatininelevel was measured by using the Jaffe

method referable to the standardizedreference measurement procedure(isotope dilution mass spectrometry),as recommended.

Statistical Methods

Thecohortwascategorizedinto groupsaccording to hypertension category,weight class, and UA gender-speci cquartiles. The continuous variables weredescribed by mean and SD and compared

across groups by Fisher-Snecodor andStudent ’s t tests. The categorical vari-ables were described by the proportionof subjects falling into each category.Proportions were compared acrossgroups by the x 2 test. Box-plots wereused to describe the distribution of UAaccording to hypertension category andweight class based groups. Correlationbetween continuous variables wasassessed by the Pearson correlation

coef cient. Multiple linear regressionwas used to assess the in uence of age,pubertal status, gender, BMI z -score (orWtHr) and eGFR on UA. The impact of UAwas considered on SBP z -score and onDBP z -score by a multiple linear re-gression model adjusting for age, pu-bertal status, gender, BMI z -score (orWtHr), and HOMA index.

Logistic regression modelswereused toassess theimpactof theaforementioned

factors on the odds ratio (OR) of beingTH, PH, and HT with respect to NT in3 separate models on the TH versusNT, PH versus NT, and HT versus NT,respectively.

No data were missing for any of the

mentioned variables. All analyses andgraphics were conducted with the pack-age R (available at http://cran.r-project.org/ ).

RESULTS

Among 648 children consecutively re-ferredtoouroutpatientclinicforCVrisk assessment between November 2004and March 2012, 147 were excluded (12

because they were , 6 years of age,and 135 because data for 1 or more of the variables included in the presentanalyses were missing). In the result-ing nal cohort of 501 subjects (55.9%boys and 44.1% girls), mean age was

10.8 years (SD = 2.4 years), 156 (31.1%)were NT, 122 (24.4%) were TH, 87(17.4%) were PH, and 136 (27.1%) wereHT. Among them, 33.3% and 40.5% wereOW or OB, respectively.

Elevated BP (PH or HT) was found in

32.1% among 131 children with NW, in42.5% among 167 OW and 54.2% among203 OB. Table 1 reports the clinicalcharacteristicsof study subjects on thebasis of the various BP categories. Asexpected, there was a trend towardhigher BMI z -score and higher percen- tages of OW or OB, increasing WtHr, andHOMA index as BP categories rose.Moreover, the prevalence of pubertal,OB, children whose WtHr was above

0.50 progressively increased from thelower to the upper BP categories. De-spite similarities in age, family historyof hypertension, renal function, fastingserum glucose, and lipid pro le, thechildren showed a signi cant rise in

TABLE 1 Clinical Characteristics of Study Subjects According to BP Category (501 Children)

NT, n = 156;31.1%

TH, n = 122;24.4%

PH, n = 87;17.4%

HT, n = 136;27.1%

P Value a

Age, y 10.5 2.2 10.7 2.3 10.8 2.5 11.1 2.6 .15Gender, boys, n (%) 83 (53.2) 68 (55.7) 50 (57.5) 79 (58.1) .85

Puberty, yes, n (%) 56 (35.9) 61 (50.0) 36 (41.4) 69 (50.7) .03Weight, kg 45.8 14.8 49.9 16.5 52.2 16.8 56.7 20.4 , .001Height, m 1.4 0.1 1.5 0.1 1.5 0.1 1.5 0.1 .19BMI, kg/m2 21.6 4.5 22.8 4.1 24.0 4.9 25.3 6.0 , .001BMI, z -score 1.04 1 .2 1.37 0.8 1.50 0.9 1.57 0.9 , .001Weight class, n (%) , .001

NW 61 (39.1) 28 (23.0) 16 (18.4) 26 (19.1)OW 42 (26.9) 54 (44.3) 29 (33.3) 42 (30.9)OB 53 (34.0) 40 (32.8) 42 (48.3) 68 (50.0)

WC, cm 71.8 12.0 74.7 11.6 77.0 11.8 79.3 13.8 , .001WtHr, % 49.8 7.4 51.1 6.2 52.8 6.5 53.6 7.7 , .001WtHr . 50%, n (%) 78 (50.0) 66 (54.1) 60 (69.0) 86 (63.2) .01SBP, mm Hg 108 7.6 113 7.1 119 5.7 130 10.5 , .001DBP, mm Hg 64 6.4 66 5.8 70 6.0 74 9.5 , .001SBP, z -score 0.40 0.56 0.73 0.46 1.37 0.26 2.14 0.37 , .001

DBP, z -score 0.20 0.53 0.38 0.50 0.70 0.54 1.03 0.76 , .001Family history of HT, n (%) 50 (32.1) 46 (37.7) 30 (34.5) 50 (36.8) .92Creatinine, mg/dL 0.52 0.10 0.53 0.12 0.53 0.11 0.55 0.13 .23eGFR, mL/min 116 19.8 118 18.2 116 18.8 114 20.5 .63UA, mg/dL 3.9 0.9 4.2 1.1 4.4 1.0 4.6 1.1 , .001Glucose, mg/dL 83 7.3 82 6.9 82 7.5 84 6.7 .10Insulin, mM/L 10.8 6.3 10.9 6.8 12.5 7.0 14.0 8.6 , .001HOMA indexb 2.23 1.39 2.25 1.47 2.55 1.45 2.93 1.87 , .001Total cholesterol, mg/dL 168 37.4 157 25.8 163 27.4 163 27.8 .03HDL cholesterol, mg/dL 58 14.1 55 13.5 55 13.9 54 12.2 .09Triglycerides, mg/dL 68 35.6 68 35.4 78 41.8 74 39.1 .10

Values are mean and SD unless otherwise indicated. HDL, high-density lipoprotein; WC, waist circumference.a P , .05 was considered statistically signi cant.b HOMA index = plasma insulin (mU/mL) 3 plasma glucose (mmol/L)/22.5.

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serum UA levels along with increasingBP levels.

The distribution of UA levels based onweight classes is shown in Fig 1. Therewas a signi cant trend in increasing UAlevels from NW to OB.

Univariateanalysis showed that among thewholestudygroup,UAwasrelatedtoage ( r = 0.38, P , .001), pubertal stage(t = – 7.68, P , .001), BMI z- score ( r =0.29, P , .001), WtHr (r = 0.27, P ,.001), eGFR (r = – 0.22, P , .001), high-density lipoprotein cholesterol ( r = –

0.26, P , .001), triglycerides ( r = 0.23, P , .001), and HOMA index (r = 0.29, P ,.001).

The relationship between UA and thesecorrelates was further investigated bymeans of multiple linear regressionanalysis. A signi cant and independentassociation with UA values was shownforage( b = 0.11, P , .001),gender ( b =0.11, P = .02), pubertal status ( b = 0.35,P = .001), BMI z -score ( b = 0.34, P ,.001), and eGFR ( b = – 0.006, P , .001).Similar results were found when WtHrwas used in the model as a measure of weight excess instead of BMI z -score.

HOMA index ceased to be signi cantlycorrelated to UA when included in thismodel (data not shown).

Univariateanalysis showed that among the whole study group, UA was signi -cantly related to both systolic BP (SBP)(z -score, r = 0.21, P , .001) and DBP(z -score, r = 0.11, P = .02).

A multiple regression model showed

that the only variables signi cantlyrelated to SBP ( z -score) were BMI(z -score) ( P , .001),HOMA index (P = .02),and serumUA ( P = .03), whereas UA andpubertal status were related to DBP(z -score) ( P = .03 and P = .02, respectively).

When WtHr was included in themultiplelinear regression model as a measureofweightexcessinsteadofBMI( z -score), the only variables signi cantly related to SBP(z -score) were WtHr ( P , .001)

and UA (P = .03), whereas WtHr was re-lated to DBP (z -score) ( P = .01). IncludingeGFR in the statistical model yieldedsuperimposable results.

Mean UA level was 4.38 (SD = 1.14) inboys and 4.15 (SD = 0.95) in girls ( t teststatistic = – 2.5, P = .01). Table 2 shows the clinical characteristics of studysubjects on the basis of gender-speci cserum UA quartiles. It can be noticed that, as UA quartiles increased, children

were more likely to be older, pubertal,and OB. Moreover, there was a trend toward higher BMI z -score, WtHr, BP

parameters, serum creatinine, and moreunfavorable HOMA index and lipid pro le.

After adjusting for pubertal status,gender, BMI z -score, and HOMA index, the OR for the presence of HT among the whole population was 1.40 (95%

con dence interval [CI] 1.12 – 1.75, P ,.01) for each 1 mg/dL increase in UAand 1.67 (95% CI 1.00– 2.82, P = .05) forsubjects in the IV UA quartile ( . 4.7mg/dL for girls; . 5.0 mg/dL for boys). Theimpact of UA was not found to be sig-ni cant when we compared childrenwith TH versus those with NT. Using NTas comparison, the risk of being PH andof being HT increased by at least 50%(OR = 1.60 and P , .01, OR = 1.54 and P

, .01, respectively, Table 3) for each 1mg/dL increase in UA, whereas it dou-bled (OR = 2.25, 95% CI 1.15– 4.38, P =.01 and OR = 2.04, 95% CI 1.12– 3.73, P =.02, respectively) for children in the IVUA quartile. The relationship between the distribution of BP categories andUA quartiles is emphasized in Fig 2.When WtHr was used instead of BMI(z -score) as a measure of weight ex-cess, the OR of being PH and of being HT

was 2.17, 95% CI = 1.10–

4.28 (P

= .03)and 1.95, 95% CI = 1.06– 3.60 (P = .03),respectively. Including eGFR in the statistical model yielded almost superim-posable results.

DISCUSSION

Inthis largegroupofchildrenatrelativelyhighCVrisk,serumUAwasindependentlyassociatedwith BPlevelsacrossdifferentBP categories, from normotension to

transientand then prehypertension, up to established hypertension.

Although the association between mildhyperuricemia and hypertension haspreviously been described in severalstudiesbothinadultsandinchildren, 1,3,4,6,26

a relationship between UA and pre-hypertension has mainly been reported inadults, 27 with only a few, relatively smallstudies carried out in children with whitecoat and borderline hypertension. 4,5,16

FIGURE 1Boxplot distribution of UA (mg/dL) in groups de ned according to weight class in 501 subjects. Boxplotexplanation: upper horizontal lineof box= 75thpercentile;lowerhorizontal lineof box= 25thpercentile;horizontal bar within box = median; square within box = mean; vertical lines out of the box = minimumand maximum. The P value displayed is referred to the overall comparison.

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Although the clinical setting of ourstudy is cross sectional, it provides uswith an opportunity to investigate thecomplex association between UA andother variables (such as insulin re-sistance, obesity, puberty, and BP) in agroup of subjects in whom pathophysi-ological mechanisms and changes lead-ing to the development of hypertension

are still at play. This is even more in- teresting in light of the recently reported nding that UA levels may bea predictor of the future development of hypertension in adults. 6

Therelationshipbetween UA andBP thatwe observed becomes clinicallyrelevantforhigherUAvalues,sincechildreninthe top UA quartile (ie, $ 5.0 mg/dL for boys

and $ 4.7 mg/dL for girls) showeda twofold higher risk of being PH and HT(Table 3 , Fig 2). On the other hand, although a trend toward higher UA valueswas present across all BP categories,UA levelscould nothelp identify children

with nonsustained hypertension.The prevalence of OW and OB was rel-atively high in our study sample, asexpected on the basis of recruitmentcriteria. Nonetheless, the associationbetween UA and BP persisted afteradjusting for BMI z -score and for WtHr,a nding that clearly supports a path-ogenetic role for serum UA in the earlyphases of hypertension development.

With the aim of better elucidating therole of UA in the development of es-sential hypertension, in the currentstudy we excluded patients with renalinsuf ciency and/or diabetes. However,we analyzed the relationship betweenUA andthose parameters, such as eGFRand HOMA index, which, even in therange of normality, could be implicatedin the development of hypertension inchildren. 13 Even slightly elevated serumUA levels have shown to be strong, in-

dependent predictors of the developmentof type 2 diabetes in adult cohorts of unselected general populations, 28 as wellas of HT patients. 29,30 Moreover, recentdata strongly support the hypothesis that insulin resistance in children mightplay a role in hypertension developmentregardless of obesity and fat distribution.13 Other variables, such as pubertyand renal function, 10,14 have also beenshown to bear an in uence on the link

between UA and BP in children.To date, only a few studies have in-vestigated the relationship of sexualmaturity 1,2 and estimated renal func- tion3,4,31 with UA and BP, and none have taken insulin resistance into consid-eration. In the current study, HOMA in-dex was found to be linearly related toUA levels and increased along with UAquartiles (Table 2), and BP categories(Table 1). However, in multiple linear

TABLE 2 Clinical Characteristics of Study Subjects on the Basis of UA Gender-Speci c Quartiles(501 Children)

I, n = 145;28.9%

II, n = 118;23.6%

III, n = 114;22.7%

IV, n = 124;24.8%

P Valuea

Age, y 9.7 2.3 10.6 2.0 11.1 2.2 11.9 2.5 , .001Gender, boys, n (%) 78 (53.8) 71 (60.2) 61 (53.5) 70 (56.5) .70Puberty, yes, n (%) 34 (23.4) 52 (44.1) 52 (45.6) 84 (67.7) , .001

Weight, kg 39.3 13.3 48.6 12.8 53.7 14.6 63.9 19.2 , .001Height, m 1.4 0.1 1.5 0.1 1.5 0.1 1.5 0.1 , .001BMI, kg/m2 20.3 4.2 22.8 4.3 24.1 4.2 26.5 5.5 , .001BMI, z -score 0.90 1.1 1.35 1.0 1.55 0.7 1.67 0.8 , .001Weight class, n (%)

NW 64 (44.1) 33 (28.0) 17 (14.9) 17 (13.7) , .001OW 43 (29.7) 39 (33.1) 50 (43.9) 35 (28.2) , .001OB 38 (26.2) 46 (39.0) 47 (41.2) 72 (58.1) , .001

WC, cm 67.3 10.9 74.8 10.5 77.2 10.1 83.9 12.7 , .001WtHr, % 48.9 6.8 51.7 6.9 52.2 6.3 54.6 7.7 , .001WtHr . 50%, n (%) 59 (40.7) 73 (61.9) 69 (60.5) 89 (71.8) , .001SBP, mm Hg 112 10.8 116 10.4 118 8.7 123 14.0 , .001DBP, mm Hg 66 7.6 67 7.5 69 6.8 71 10.0 , .001SBP, z -score 0.93 0 .87 1.06 0.79 1.20 0 .70 1.32 0 .88 , .001DBP, z -score 0.49 0.69 0.50 0.64 0.56 0.60 0.69 0.76 .08Family history of HTN, n (%) 50 (34.5) 39 (33.1) 43 (37.7) 44 (35.5) .68Creatinine, mg/dL 0.48 0.10 0.53 0.09 0.54 0.11 0.59 0.13 , .001eGFR, mL/min 121 20.4 115 18.0 116 19.1 111 18.6 , .001UA, mg/dL 3.1 0.4 4.0 0.2 4.6 0.2 5.7 0.7 , .001Glucose, mg/dL 83 6.1 82 7.6 84 7.4 83 7.6 .33Insulin, mM/L 9.1 5.5 11.3 6.6 13.0 7.9 15.0 8.0 , .001HOMA indexb 1.88 1.14 2.33 1.44 2.73 1.76 3.10 1.73 , .001Total cholesterol, mg/dL 168 36.4 161 27.1 163 27.1 160 30.0 .14HDL cholesterol, mg/dL 60 13.2 57 14.1 53 11.6 50 12.6 , .001Triglycerides, mg/dL 60 26.5 64 36.5 77 35.9 85 46.1 , .001

Values are mean and SD unless otherwise indicated.UA gender-speci c quartiles ( # 3.6 mg/dL, . 3.6 mg/dL and # 4.1, . 4.1 mg/dL and # 4.7 mg/dL, . 4.7 mg/dL for girls, # 3.6mg/dL, . 3.6 mg/dL and # 4.3, . 4.3 mg/dL and # 5.0 mg/dL, . 5.0 mg/dL for boys).HDL, high-density lipoprotein; WC, waist circumference.a P , .05 was considered statistically signi cant.b HOMA index = plasma insulin (mU/mL) 3 plasma glucose (mmol/L)/22.5.

TABLE 3 Effect of Pubertal Status, Gender, BMI, UA (as continuous measure), and HOMA index on the risk of TH versus NT, PH versus NT, and HT versus NT

Variable TH versus NT, n = 278 PH versus NT, n = 243 HT versus NT, n = 292

OR (95% CI) P a OR (95% CI) P a OR (95% CI) P a

Puberty, Yes 1.97 (1.13 – 3.43) .01 1.09 (0.58– 2.06) .78 1.47 (0.84– 2.57) .17Gender, boys 1.11 (0.67 – 1.84) .69 1.15 (0.65– 2.03) .64 1.29 (0.78– 2.15) .32BMI, z - score 1.53 (1.15 – 2.05) , .01 1.43 (1.03– 1.99) .03 1.44 (1.07– 1.93) .02UA, mg/dL 1.17 (0.89– 1.54) .26 1.60 (1.15– 2.22) , .01 1.54 (1.17– 2.03) , .01HOMA indexb 0.82 (0 .67– 1.01) .06 0.96 (0.77– 1.19) .70 1.06 (0.89– 1.27) .50a P , .05 was considered statistically signi cant.b HOMA index = plasma insulin (mU/mL) 3 plasma glucose (mmol/L)/22.5.

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and logistic regression analysis, therelationship between this marker of insulin resistance and BP levels andcategories almost completely loses itsstrength, whereas serum UA maintains

its independent link to BP. Although theseresults cannot help to de ne whetherserum UA is in uenced by BP elevationand insulin resistance or vice versa, theycertainly point toward a complex re-lationship among these factors.

Asforrenalfunction,wefoundthateGFRwassimilar in allBP categories, andtheaddition of this variable to linear andlogistic regression analyses left the re-lationshipbetweenUAandBPunchanged.

Even accounting for body mass and pu-berty, the independent role of UA varia- tions on BP values did not decrease.

Our data con rm and expand thosepreviously reported by Loef er et al 3 ina large study conducted on a repre-sentative sample of adolescents in theUnited States. In fact, we were fortunateenough to obtain a larger study samplefrom our records and therefore wereable to demonstrate an association

between SBP as well as DBP and serumUA levels even in a fully adjusted multi-variate linear regression analysis.

Our study has both strengths andweaknesses that deserve to be com-mented on. Among the former, the fact that, unlike other previous large stud-ies, 3 the de nition of elevated BP and the allocation of children into differentBP categories was not based on a sin-gle physical examination. BP was mea-sured in at least 2 different occasions:previously by the family pediatricianand then again in our clinic, and in bothcases the mean of 3 measurementswasused for analysis. To fully account for

age, gender, and height, according to the tablespublished in the fourth reporton the diagnosis, evaluation, and treat-ment in children and adolescents, 23 weused BP z -scores rather than raw BPvalues, which makes our observationsmore reliable as compared with thoseof a variety of previous reports. 1,2,4,6,16

Furthermore, to the best of our knowl-edge, for the rst time several clinicaland biohumoral variables have been

concurrently collected and analyzed ina group of referred children.

Last, there are some limitations to ourstudy. First, given the cross-sectionalnature of its design, it would be in-appropriate to derive de nitive con-

clusions regarding the cause-effectrelationship between UA and BP levels,even though the association we reportpersistedevenwhenseveral well-knownconfounding factors were taken intoaccount. Second, the lack of a controlgroup may limit the implications of ourobservations. Nevertheless, within thecontextofchildrenwithrelativelyhighCVrisk, our data show a clear trend in theBP-UA associationalongwithprogressively

worse BP categories, from transient to established hypertension. Higher UAlevels showa signi cant association with the occurrence of higher BP levels evenamong a cohort of children at relativelyhigh CV risk. Third, ambulatory bloodpressure monitoring was not performedin our study and therefore we could notclassify any subject into the “ white-coathypertension ” or “ masked hypertension ”

category. However, there is a general

consensus in current pediatric literature that diagnosisofhypertension inchildrenand adolescents be based on of ce BPmeasures and not on ambulatory bloodpressure monitoring.

CONCLUSIONS

In children at relatively high CV risk, UAshows a strong relationship with BPvalues across different BP categories,from normal BP to transient, up to pre-

and nally to established hypertension.The association between UA and BPlevels is independent of several well-known factors potentially implicated in the development of hypertension, such asinsulin resistance, pubertal stage, andrenal function. These data support theneed for further large, prospective, andinterventional studies to clarify the path-ophysiologicalmechanismsunderlyingtherelationship between serum UA and BP.

FIGURE 2Distributionof BP categories according to UAquartiles. Stackedbarplotof BPcategoryin groupsde nedaccording to UA quartiles (I = # 3.6 mg/dL, II =. 3.6 mg/dL and # 4.1, III =. 4.1 mg/dL and # 4.7 mg/dL,IV =. 4.7 mg/dL for girls; I = # 3.6 mg/dL, II =. 3.6 mg/dL and # 4.3, III =. 4.3 mg/dL and # 5.0 mg/dL,IV =. 5.0mg/dLfor boys) in 501subjects. Usingthe NTas comparison, theadjusted risk of being PH(OR= 2.25, 95% CI 1.15– 4.38, P = .01) and of being HT (OR = 2.04, 95% CI 1.12– 3.73, P = .02) doubled forchildren in IV UA quartile. The P value displayed refers to the overall comparison.

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DOI: 10.1542/peds.2013-0047; originally published online June 17, 2013;2013;132;e93Pediatrics

Simonetta GenovesiSilvana Mastriani, Andrea Stella, Roberto Pontremoli, Maria Grazia Valsecchi andFrancesca Viazzi, Laura Antolini, Marco Giussani, Paolo Brambilla, Sara Galbiati,

Serum Uric Acid and Blood Pressure in Children at Cardiovascular Risk

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mlhttp://pediatrics.aappublications.org/content/132/1/e93.full.htincluding high resolution figures, can be found at:

References

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DOI: 10.1542/peds.2013-0047; originally published online June 17, 2013;2013;132;e93Pediatrics

Simonetta GenovesiSilvana Mastriani, Andrea Stella, Roberto Pontremoli, Maria Grazia Valsecchi andFrancesca Viazzi, Laura Antolini, Marco Giussani, Paolo Brambilla, Sara Galbiati,

Serum Uric Acid and Blood Pressure in Children at Cardiovascular Risk

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of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academypublished, and trademarked by the American Academy of Pediatrics, 141 Northwest Point

publication, it has been published continuously since 1948. PEDIATRICS is owned,PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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acido urico en presion aterial en riesgo cv

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