Published online before print January 26, 2004, doi: 10.1161/01.HYP.0000114696.96318.4e
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2004;43:214.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Cardiovascular Risk Factors and Sequelae in Hypertensive Children Identified by Referral Versus School-Based Screening
From Department of Pediatrics (J.M.S., J.T., F.W., R.J.P.), University of Texas-Houston Medical School, Houston; Department of Neurology (Z.G., A.V.A.), University of Texas-Houston Medical School, Houston; Wyle Laboratories (D.S.M., K.G.), NASA Johnson Space Center Cardiovascular Laboratory, Houston, Tex.
Correspondence to Dr Jonathan M. Sorof, Associate Professor, Division of Pediatric Nephrology and Hypertension, University of Texas-Houston, Medical School, 6431 Fannin St, Rm 3.124, Houston, TX 77030. E-mail jonathan.m.sorof{at}uth.tmc.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
To determine whether systematic differences exist between hypertensive children referred for evaluation by primary care providers and children identified through community-based screening, cardiovascular risk factors and surrogate markers of hypertensive injury were compared based on subject source (referral versus screening). Children referred to a hypertension clinic for persistently elevated blood pressure were compared with children identified as hypertensive during school screening of 5102 students in Houston public schools. M-mode echocardiography of the left ventricle was performed and subsequently reviewed by 2 independent sonographers blinded to identifying subject information. Subsets of subjects also underwent carotid artery ultrasound for measurement of intimal-medial thickness, overnight urine collections for microalbuminuria, and fasting serum cholesterol, triglycerides, and glucose. Ninety-seven total subjects (54 screening and 43 referral) met inclusion criteria and had technically adequate echocardiography performed. The prevalence of left ventricular hypertrophy (LVH) was 37%. Referral subjects demonstrated significantly greater left ventricular mass index (38.8 versus 34.2 g/m2.7; P<0.01) and a higher prevalence of LVH (49% versus 28%; P<0.05). Among subjects who underwent carotid ultrasound (n=75), carotid intimal-medial thickness was significantly higher in referral subjects (0.61 versus 0.57, P<0.05). When controlling for BMI z score, which was significantly higher in referral subjects, systematic differences by subject source did not persist. These findings suggest that hypertensive children who are predominantly overweight, independent of the manner in which patients come to medical attention, will manifest evidence of more severe cardiovascular disease assessed by surrogate markers such as left ventricular mass index or carotid artery intimal medial thickness.
Key Words: obesity • hypertension • children • echocardiography • cardiovascular diseases
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
As the prevalence of primary pediatric hypertension has been increasing in association with the obesity epidemic,1 increased attention has focused on the characterization of cardiovascular sequelae in children with elevated blood pressure. Because morbid cardiovascular events are rare except in the most severely hypertensive children, investigation has relied on surrogate markers of hypertensive injury such as left ventricular mass index (LVMI) and carotid artery intimal medial thickness (cIMT). Recent studies have shown that LVMI2 and cIMT3 are increased in hypertensive as compared with normotensive children and that these increases occur in parallel.4 In hypertensive children, the reported prevalence of left ventricular hypertrophy (LVH) ranges from 10% to 38%,5–12 depending on the echocardiography protocol used to derive LVM, the method of indexing LVM to standardize across the range of pediatric age and size, and the threshold used to define LVH in children. A recent, retrospective, multicenter study of 129 children undergoing evaluation for hypertension found an overall prevalence of LVH of 41%.13 However, the study was limited by several factors that included an exclusively referral-based subject population.
Most recent studies investigating hypertension and its sequelae in children have consisted of convenience sampling of patients referred to a tertiary care subspecialty hypertension clinic.2,11,14–17 This sampling strategy creates the potential for systematic differences from the general population of hypertension children because of factors such as better access to health care, different anthropometric characteristics, greater severity of blood pressure elevation, and longer duration of disease. These issues impact the external validity of clinic-based pediatric hypertension research and might determine the relative benefit of community-based hypertension screening in children. To determine whether systematic differences exist between hypertensive children referred for evaluation by primary care providers and previously undiagnosed hypertension in children identified through community-based screening, cardiovascular risk factors and surrogate markers of hypertensive injury were compared based on subject source.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
All patients newly referred to the pediatric hypertension clinic from January 2002 through May 2003 were approached for participation in a study of target organ damage in hypertensive children. To be considered for further analysis, criteria for inclusion of referral subjects consisted of: (1) casual blood pressure (BP) elevation above the 95th percentile on at least 2 previous occasions by report of the referring health care provider; (2) no known underlying medical conditions predisposing to hypertension; (3) no past or concurrent antihypertensive medications; (4) no concurrent medication with the potential to raise BP (eg, prednisone or methylphenidate); and (5) age between 8 and 18 years to match the age range of screening subjects.
School-based hypertension and obesity screening was performed in 5102 students in 8 Houston public schools from May 2002 to November 2002. Parents were notified in advance by letter sent from each school regarding the screening program. Forms were provided for parents to sign and return if they did not wish their child to participate. At each screening, three seated blood pressure measurements were made at least one-minute apart using oscillometric monitors. Students found to have an average blood pressure above the gender, age and height-percentile specific 95th percentile blood pressure value18 underwent a second set of blood pressure measurements 1 to 2 weeks later. Students found to have blood pressure above the 95th percentile at the second screening underwent a third set of blood pressure measurements an additional 1 to 2 weeks later. Students found to have elevated blood pressure on all three occasions were considered to be hypertensive. Families of hypertensive children were informed of the persistent blood pressure elevation and invited to participate in a clinic-based study of hypertensive end-organ injury in children. The protocol was approved by the Institutional Committee for the Protection of Human Subjects.
Age was determined based on the date of first contact in the clinic. Gender and ethnicity were self-described. Weight and height were measured in each student, and body mass index (BMI) was calculated as weight/height (kg/m2). The most current pediatric anthropometric reference data specific for gender and age was used to establish height, weight, and BMI percentile for each subject.19 Exact BMI z scores were generated from equations provided by the Centers for Disease Control and Prevention. "Overweight" was defined as BMI 
95th percentile. All subjects underwent auscultatory mercury manometer blood pressure measurements in the clinic at the initiation of further study participation, which were used for analysis of clinic blood pressure values. An index of severity of blood pressure elevation (BP index) was calculated by dividing the subject’s blood pressure by the subject-specific 95th percentile blood pressure value.
All subjects underwent 2-dimensionally guided M-mode echocardiography of the left ventricle from a parasternal longitudinal axis image and a short axis image at the level of the papillary muscles with the patient in the left lateral decubitus position. M-mode echocardiography was recorded on videotape by the clinical sonographer and then digitized for off-line analysis. Digitized images were reviewed by two independent, experienced, research sonographers. Research sonographers were blinded to all identifying subject information including demographic or anthropometric data, hypertensive status (normal or hypertensive), and subject source (referral versus screening). Measurements of the LV end-diastolic dimension (LVED), interventricular septal thickness (IVS), and posterior wall thickness (PWT) were made during diastole according to methods established by the American Society of Echocardiography. Each LV parameter was measured during 4 diastolic cycles by both sonographers. Subjects whose videotapes were found technically inadequate for accurate LV measurements were excluded from further analysis. The average of all measurements (8 per parameter) was used to calculate LVM using the Devereux equation.20 LVMI was calculated by dividing LVM by height2.7 to account for gender, age, and ethnic differences in LVM.21,22
A subset of subjects underwent carotid artery ultrasound performed by experienced vascular sonographers according to a standardized scanning protocol. Sonographers were blinded to hypertensive status and subject source. A longitudinal view of the distal common carotid artery (CCA) was obtained using a linear 10-MHz transducer. The gain and focus settings were optimized to contrast the vessel lumen and IMT appearance. Two IMT measurements were made on the far wall of the distal CCA on each side. A longitudinal B-mode image of the CCA with sharp edges of the far wall IMT complex was used to place 2 measurements with digital calipers at 1 cm apart. The first measurement was made within 1 cm of the carotid bulb, and the second measurement was made 1 cm proximal from the first measurement. The measurements were performed on frozen images demonstrating the thickest IMT complex with calipers placed on a zoomed CCA image. The mean of four IMT measurements (2 on each side) for each subject was used as the value for analysis (cIMT).
An additional subset of subjects underwent assessment of microalbuminuria and fasting metabolic studies. From an overnight urine collection, urinary albumin-to-creatinine ratio (Alb/Cr) was calculated by dividing urinary albumin (mg/L) by urinary creatinine (mg/dL). Subjects also underwent fasting assessment of AM serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and glucose.
Descriptive statistics are presented as percentages, means, and standard deviations. Univariate analyses for group comparisons of continuous variables were performed using Student t test. Multivariate analyses for group comparisons were performed using analysis of covariance. The correlation between LVMI and continuous variables was determined using the Pearson correlation coefficient. Multiple regression analysis was used to determine the strength of association between LVMI and multiple independent variables. 
2 test was used to analyze the relative percentage of categorical variables by group. P<0.05 indicated statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Ninety-seven total subjects (54 screening subjects and 43 referral subjects) met inclusion criteria and had echocardiography studies of sufficient quality for off-line analysis. Hypertension was confirmed by clinic blood pressure values in 83% (45/54) of screening subjects and in 84% (36/43) of referral subjects. No secondary causes for hypertension were found among either category of subject. Subjects with hypertensive and normotensive clinic blood pressure values were included in the analyses. The overall prevalence of LVH was 37% (36/97), which did not vary based on the presence or absence of confirmed clinic hypertension (37% versus 37%). The prevalence of overweight (BMI >95th percentile for age and gender) was 45% (44/97).
To determine whether the 54 participating screening subjects were a representative sample of the overall group of 221 persistently hypertensive children from the screening program, the subgroup of screening participants was compared with the total group of screening hypertensives based on demographic, anthropometric, and clinical variables. Participants as compared with the total group were similar for all variables including age (13.8 versus 13.4 years), male gender percentage (54% versus 61%), BMI (26 versus 25 kg/m2), and blood pressure values at first screening (134/72 versus 135/71 mm Hg), second screening (137/75 versus 135/75 mm Hg), and third screening (134/75 versus 134/74 mm Hg).
The primary analyses were the comparisons of screening subjects with referral subjects. Comparisons of demographic, anthropometric, and clinical data by subject source are shown in Table 1. Referral subjects were more likely to be male (77% versus 54%; P<0.05). There were no significant differences by ethnicity. Referral subjects were heavier and had higher BMI than screening subjects but did not differ significantly by age or height. The prevalence of overweight was 58% in referral subjects compared with 35% in screening subjects (P<0.05). Referral subjects had higher raw clinic SBP than screening subjects (P<0.05); however, the SBP index (severity of systolic blood pressure elevation) did not differ by subject source. Neither raw nor indexed DBP values differed by subject source.
|
Univariate comparison by subject source for hypertensive surrogate markers and metabolic risk factors are shown in Table 2. Referral subjects demonstrated significantly greater LVMI (P<0.01), as well as greater LVED and PWT. The prevalence of LVH was significantly higher among referral subjects as compared with screening subjects (49% versus 28%, P<0.05). Among the subset of 75 subjects who underwent carotid ultrasound, cIMT was significantly higher in referral versus screening subjects (P<0.05). Among the subset of 77 subjects who underwent overnight urine collection for albumin and creatinine, Alb/Cr ratio show a slight trend to be higher in the referral subjects but the difference was not statistically significantly. Among the subset of 59 subjects who underwent assessment of fasting serum metabolic factors, no differences were found in cholesterol, HDL, LDL, triglycerides, or glucose.
|
To assess for potential confounding factors in the analysis of subject source on surrogate markers of disease, multivariate analysis was performed to adjust for other demographic and anthropometric variables. Variables that showed systematic differences by subject source (gender, clinic SBP, and BMI z score) were included in the analysis. Because of strong intercorrelations between weight, BMI, BMI percentile, and BMI z score, only BMI z score was included in the multivariate analysis. After simultaneous adjustment for potential confounders of the relationship between subject source and LVMI, only BMI z score was significantly associated with LVMI. Specifically, the effect of subject source was no longer significant after adjustment for BMI z score. LVMI and BMI were significantly and independently associated (r=0.50, P<0.001) (Figure ). A similar multivariate analysis for cIMT showed that the effect of subject source on cIMT was no longer significant after adjustment for BMI z score. cIMT and BMI were also significantly and independently associated (r=0.38, P<0.001).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The issue of subject source has important implications for determining the external validity of pediatric hypertension research. Because investigation of the causes and consequences of hypertension during childhood has been limited to some extent by the ability to recruit study subjects, many recent studies on pediatric hypertension have been conducted in subjects identified by referral to subspecialty clinics by primary care providers.14–16,23–27 This convenience sampling of patients referred to a subspecialty clinic may lead to the study of children who fail to represent the overall population of hypertensive children in the community. The current study found that referral subjects differed systematically from subjects identified through community screening with respect to the anthropometric characteristics and the extent of abnormality of surrogate markers of cardiovascular disease. Overall, the referral group had a male predominance and was more overweight by all measures of body habitus (weight, BMI, BMI percentile, prevalence of overweight). Referral subjects also had higher raw SBP values, although the severity of blood pressure elevation was not different when indexed to the subject-specific 95th percentile. The referral group had higher LVMI, a greater prevalence of LVH, and higher cIMT values. It is uncertain whether these differences by subject source are of a general or a site-specific nature. However, these findings suggest that group comparisons of cardiovascular sequelae in hypertensive children need to account for systematic differences in other factors known to influence surrogate markers of disease.
The systematic differences in cardiovascular markers by subject source in the current study appeared to be mainly attributable to differences in body habitus. Specifically, the significantly higher LVMI and cIMT in referral as compared with screening subjects did not persist when controlling for BMI z score. Further analysis revealed that BMI z score was significantly associated with metabolic cardiovascular risk factors (ie, fasting total cholesterol, LDL cholesterol, and triglycerides) and with surrogate markers of hypertensive sequelae (ie, LVMI, cIMT). These findings are consistent with previous studies by Urbina et al28 and Daniels et al,29 who reported that measures of ponderosity are significant determinants of LVM in children. In a multicenter study by Hanevold et al, the single strongest determinant of LVMI was BMI. We have previously reported significant positive associations between BMI and LVMI2 and cIMT.3 Of note, the current study found no association between raw or indexed blood pressure values and markers of hypertensive sequelae. Thus, an accumulation of evidence suggests that overweight may be the greatest risk factor for target organ changes in children with elevated blood pressure.
This confounding influence of BMI z score affects the interpretation of the primary comparison by subject source. Although LVMI and cIMT were higher in referral subjects by univariate analysis, neither difference remained significant when controlling for the overall higher BMI z score in the referral subjects. This systematic difference in body habitus by subject source is also illustrated by the higher prevalence of overweight in the referral compared with screening subjects (58% versus 35%). Of note, raw SBP values remained higher in the referral subjects even when controlling for BMI z score. Thus, although referral subjects did demonstrate evidence of more severe cardiovascular disease risk and outcome, the implication of this finding for clinic-based pediatric hypertension research is not entirely clear. However, these findings do suggest that any group of study subjects that is predominantly overweight, independent of other factors such as subject source or hypertension severity, will show evidence of more severe incipient cardiovascular disease.
The current study is confirmatory of previous studies showing that LVH is highly prevalent in children with cardiovascular risk factors.10,11,13,14 Using published reference data on the pediatric 95th percentile of LVM indexed to height2.7,21 the prevalence of LVH was found to be 37%. Among the more severely overweight referral subjects, the prevalence of LVH was found to be even higher at 49%. These results are consistent with previous studies of cardiac remodeling in children with cardiovascular risk factors. Using the methodology for indexing LVM and defining LVH as in the current study, Daniels et al first reported a prevalence of LVH of 38.5% in 104 children with blood pressure greater than the 90th percentile evaluated in a subspecialty hypertension clinic.10 Hanevold et al pooled data from three different centers in 133 children undergoing evaluation in a hypertension clinic setting and found a prevalence of LVH of 41%.13 In the current study, multiple measurements were made of each LV parameter by two independent sonographers who did not participate in the echocardiographic image acquisition and were therefore blinded to any identifying demographic or clinical information about the subjects. This approach provided a centralized, accurate, and unbiased set of measurements for calculation of LVMI and lends a high degree of credence to the study results.
Perspectives
The external validity of clinic-based research is an issue of importance for virtually all research questions with public health implications. Based on the results of the current study, weight, not subject source, is the most important confounding variable when studying childhood hypertension. Specifically, the extent of abnormality of surrogate markers of cardiovascular disease did not differ by subject source when adjusted for body habitus. Nonetheless, important systematic differences between referral and screening subjects were found that in aggregate cast doubt on whether the study of children in the clinic setting accurately represents the disease process in the general population. The current study also touches on the issue of whether systematic screening for childhood hypertension is indicated and/or cost-effective. Further studies are needed to determine whether early identification is an effective strategy for preventing or ameliorating clinical cardiovascular morbidity as at risk children reach adulthood.
|
Footnotes |
|---|
Research supported by a National Heart, Lung, and Blood Institute grant from K23 HL04217.
Received September 11, 2003; first decision September 20, 2003; accepted November 25, 2003.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Sorof J, Daniels S. Obesity hypertension in children: a problem of epidemic proportions. Hypertension. 2002; 40: 441–447.
2. Sorof JM, Cardwell G, Franco K, Portman RJ. Ambulatory blood pressure and left ventricular mass index in hypertensive children. Hypertension. 2002; 39: 903–908.
3. Sorof JM, Alexandrov AV, Garami Z, Turner JL, Grafe RE, Lai D, Portman RJ. Carotid ultrasonography for detection of vascular abnormalities in hypertensive children. Pediatr Nephrol. 2003; 18: 1020–1024.[CrossRef][Medline] [Order article via Infotrieve]
4. Sorof JM, Alexandrov AV, Cardwell G, Portman RJ. Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics. 2003; 111: 61–66.
5. Goldring D, Hernandez A, Choi S, Lee JY, Londe S, Lindgren FT, Burton RM. Blood pressure in a high school population. II. Clinical profile of the juvenile hypertensive. J Pediatr. 1979; 95: 298–304.[CrossRef][Medline] [Order article via Infotrieve]
6. Laird WP, Fixler DE. Left ventricular hypertrophy in adolescents with elevated blood pressure: assessment by chest roentgenography, electrocardiography, and echocardiography. Pediatrics. 1981; 67: 255–259.
7. Culpepper WS, Sodt PC, Messerli FH, Ruschhaupt DG, Arcilla RA. Cardiac status in juvenile borderline hypertension. Ann Intern Med. 1983; 98: 1–7.
8. Schieken RM, Clarke WR, Lauer RM. Left ventricular hypertrophy in children with blood pressures in the upper quintile of the distribution. The Muscatine Study. Hypertension. 1981; 3: 669–675.
9. Richter R. [Echocardiography studies of children and adolescents with primary hypertension] Echokardiographische Untersuchungen von Kindern und Jugendlichen mit primarer Hypertonie. Kinderarztl Prax. 1993; 61: 279–284.[Medline] [Order article via Infotrieve]
10. Daniels SR, Meyer RA, Loggie JM. Determinants of cardiac involvement in children and adolescents with essential hypertension. Circulation. 1990; 82: 1243–1248.
11. Belsha CW, Wells TG, McNiece KL, Seib PM, Plummer JK, Berry PL. Influence of diurnal blood pressure variations on target organ abnormalities in adolescents with mild essential hypertension. Am J Hypertens. 1998; 11: 410–417.[CrossRef][Medline] [Order article via Infotrieve]
12. Johnson MC, Bergersen LJ, Beck A, Dick G, Cole BR. Diastolic function and tachycardia in hypertensive children. Am J Hypertens. 1999; 12: 1009–1014.[CrossRef][Medline] [Order article via Infotrieve]
13. Hanevold C, Waller J, Daniels SR, Portman RJ, Sorof JM. The effects of obesity, sex, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children: A collaborative study of the International Pediatric Hypertension Association. Pediatrics. 2003; In press.
14. Daniels SR, Loggie JM, Khoury P, Kimball TR. Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension. Circulation. 1998; 97: 1907–1911.
15. Sorof JM, Portman RJ. White coat hypertension in children with elevated casual blood pressure. J Pediatr. 2000; 137: 493–497.[CrossRef][Medline] [Order article via Infotrieve]
16. Flynn JT. Differentiation between primary and secondary hypertension in children using ambulatory blood pressure monitoring. Pediatrics. 2002; 110: 89–93.
17. Daniels SR, Witt SA, Glascock B, Khoury PR, Kimball TR. Left atrial size in children with hypertension: the influence of obesity, blood pressure, and left ventricular mass. J Pediatr. 2002; 141: 186–190.[CrossRef][Medline] [Order article via Infotrieve]
18. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics. 1996; 98: 649–658.
19. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, Mei Z, Curtin LR, Roche AF, Johnson CL. CDC growth charts: United States. Adv Data. 2000: 1–27.
20. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986; 57: 450–458.[CrossRef][Medline] [Order article via Infotrieve]
21. Daniels SR, Kimball TR, Morrison JA, Khoury P, Meyer RA. Indexing left ventricular mass to account for differences in body size in children and adolescents without cardiovascular disease. Am J Cardiol. 1995; 76: 699–701.[CrossRef][Medline] [Order article via Infotrieve]
22. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, Alderman MH. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992; 20: 1251–1260.[Abstract]
23. Khan IA, Gajaria M, Stephens D, Balfe JW. Ambulatory blood pressure monitoring in children: a large center’s experience. Pediatr Nephrol. 2000; 14: 802–805.[CrossRef][Medline] [Order article via Infotrieve]
24. Sorof JM, Poffenbarger T, Franco K, Portman R. Evaluation of white coat hypertension in children: importance of the definitions of normal ambulatory blood pressure and the severity of casual hypertension. Am J Hypertens. 2001; 14: 855–860.[CrossRef][Medline] [Order article via Infotrieve]
25. Matsuoka S, Kawamura K, Honda M, Awazu M. White coat effect and white coat hypertension in pediatric patients. Pediatr Nephrol. 2002; 17: 950–953.[CrossRef][Medline] [Order article via Infotrieve]
26. Feig DI, Johnson RJ. Hyperuricemia in Childhood Primary Hypertension. Hypertension. 2003; In press.
27. Sieber US, Von Vigier RO, Sforzini C, Fossali E, Edefonti A, Bianchetti MG. How good is blood pressure control among treated hypertensive children and adolescents? J Hypertens. 2003; 21: 633–637.[CrossRef][Medline] [Order article via Infotrieve]
28. Urbina EM, Gidding SS, Bao W, Pickoff AS, Berdusis K, Berenson GS. Effect of body size, ponderosity, and blood pressure on left ventricular growth in children and young adults in the Bogalusa Heart Study. Circulation. 1995; 91: 2400–2406.
29. Daniels SR, Kimball TR, Morrison JA, Khoury P, Witt S, Meyer RA. Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. Statistical, biological, and clinical significance. Circulation. 1995; 92: 3249–3254.
This article has been cited by other articles:
 |
|
 |
|
  A. Chiolero, G. Paradis, G. Madeleine, J. A. Hanley, F. Paccaud, and P. Bovet Discordant Secular Trends in Elevated Blood Pressure and Obesity in Children and Adolescents in a Rapidly Developing Country Circulation, February 3, 2009; 119(4): 558 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Podoll, M. Grenier, B. Croix, and D. I. Feig Inaccuracy in Pediatric Outpatient Blood Pressure Measurement Pediatrics, March 1, 2007; 119(3): e538 - e543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pinto, R. Roldan, and T. P. Sollecito Hypertension in children: an overview. J Dent Educ., April 1, 2006; 70(4): 434 - 440. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||