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PEDIATRICS Vol. 110 No. 1 July 2002, pp. 89-93

Differentiation Between Primary and Secondary Hypertension in Children Using Ambulatory Blood Pressure Monitoring

Joseph T. Flynn, MD

From the Division of Pediatric Nephrology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Objective. To determine whether ambulatory blood pressure monitoring (ABPM) can help differentiate children with secondary hypertension from those with primary hypertension.

Methods. Ninety-seven ABPM studies obtained from 85 children followed in a pediatric hypertension clinic were analyzed. Forty studies were performed in patients with primary hypertension, and 57 studies were performed in patients with secondary hypertension. Mean patient age was 13.8 ± 3.5 [mean ± standard deviation] years, range 4 to 19.7 years; patients with secondary hypertension were younger and had lower body mass index than patients with primary hypertension.

Results. Daytime diastolic and nocturnal systolic blood pressure (BP) loads, defined as the percentage of readings greater than a threshold value, were significantly greater in patients with secondary hypertension compared with patients with primary hypertension. A daytime diastolic BP load of ≥25% and/or a nocturnal systolic BP load of ≥50% was highly specific for secondary hypertension.

Conclusions. Secondary hypertension in childhood is characterized by daytime diastolic BP elevation and nocturnal systolic BP elevation. This pattern of hypertension on ABPM may be a clue to underlying renal or other organ system pathology in children being evaluated for suspected hypertension and could help to identify children who require more detailed evaluation to determine the cause of their hypertension.

Key Words: children • hypertension • ambulatory blood pressure monitoring • diagnostic testing

Abbreviations: ABPM, ambulatory blood pressure monitoring • BP, blood pressure • BMI, body mass index


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Once a child has been identified as having hypertension, it is customary to proceed with a sometimes exhaustive diagnostic evaluation to identify any underlying condition that may be causing the hypertension. Such evaluations are certainly reasonable in younger children or in adolescents with severe hypertension—2 groups of patients in whom secondary hypertension would be likely.1–3 However, in many children with less severe hypertension, especially adolescents, an extensive diagnostic evaluation may not be necessary if primary hypertension is suspected.3,4

At present, however, there are no widely used studies that can readily differentiate between primary and secondary hypertension in such patients, meaning that many children may receive more extensive testing than necessary. Studies in hypertensive adults have indicated that ambulatory blood pressure monitoring (ABPM), a technique in which a particpant’s blood pressure (BP) is measured over a 24-hour period, may be useful in this situation.5,6 In this study, we reviewed our experience with ABPM in children to determine whether this technique could be used to differentiate between primary and secondary hypertension.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
This study consisted of a retrospective review of all ABPM studies obtained in the University of Michigan Pediatric Hypertension Program between January 1996 and December 2000. As previously described,7 ABPM studies were performed after the child’s encounter with the clinic physician. Monitors were placed on the child’s nondominant arm by a trained nurse who then educated the child and their family regarding operation of the monitor. The nurse obtained 1 or 2 BPs using the monitor, recorded these values, and then obtained 1 to 2 additional BPs in the child’s other arm using either an automated oscillometric device (Dinamap, Critikon Inc, Tampa, FL) or manual aneroid sphygmomanometer. Monitor readings were accepted as accurate if they were within 5 to 10 mm Hg of these readings for both systolic and diastolic BP. After these initial readings, participants were blinded to the monitor BP readings.

Monitors were programmed to obtain BP readings every 20 minutes during the day (6 AM-10 PM) and every 30 minutes at night (10:01 PM-5:59 AM). SpaceLabs 90207 or 90217 monitors (SpaceLabs Medical, Inc, Redmond, WA) were used for all studies. This monitor is programmed to estimate the fifth Korotkoff sound (K5) as the diastolic BP. The recommendations of the Working Group4 were followed with respect to selection of cuff size.

ABPM data from the monitor were downloaded into a desktop personal computer once the device was returned. Readings were compared by the analysis software to a threshold value, thereby categorizing the readings as either normal or elevated. The daytime threshold reading for all children was set at the 95th percentile for participant’s age, gender, and height as determined by the Working Group.4 Nocturnal thresholds were set 10% below the daytime thresholds for all children. The patient’s self-reported wake/sleep periods were used to determine the daytime and nocturnal portions of the ABPM studies. The analysis software was individually programmed for each ABPM study. No manual editing of the monitor readings was performed.

Definitions
Hypertension in all children was defined as sustained BP elevation above the 95th percentile for age, gender, and height as recommended by the Working Group.4 This diagnosis was based on casual BPs obtained in our clinic before ABPM was performed. In addition, for inclusion in this study, patients had to have a systolic and/or diastolic BP load (see below) of >30% for either the daytime or nocturnal portion of the ABPM study.

Children were classified as having either primary or secondary hypertension following a standardized, comprehensive diagnostic evaluation3 that included appropriate laboratory and radiographic studies as recommended by consensus groups such as the Second Task Force.1 When ABPM was included in the initial evaluation of newly diagnosed patients, it was used as an adjunct to the standard set of diagnostic studies, and was not used to determine the underlying diagnosis.

BP load8 was defined as the percentage of readings greater than the threshold value defined above. Dipping status was examined by comparing the mean daytime BP value to the mean nocturnal BP value. Percent dipping for both systolic and diastolic BP was calculated as: [(daytime BP–nocturnal BP) ÷ daytime BP] x 100.

Data Analysis
Data in this report are expressed as mean ± standard deviation, or as percentages. Statistical analysis was performed using SPSS for Windows 10.0.5 (SPSS Inc, Chicago, IL). Two-tailed, unpaired t tests were used to examine differences between group means. Fisher exact test was used to determine the difference in group proportions. Statistical significance was set at P < .05 for all analyses.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Patients
A total of 107 ABPM studies were performed during the study period (January 1996-December 2000). Indications for ABPM included both diagnostic evaluation of newly referred patients, as well as assessment of BP control in hypertensive children receiving drug therapy. Ten studies were subsequently excluded from analysis, 3 in patients determined to be normotensive, 4 because of > 50% missing data because of monitor malfunction or poor patient cooperation, and 3 that were performed to evaluate patients for suspected hypotension. Thus, 97 studies were available for analysis. Forty-four of these were performed in untreated patients, and 53 were performed in patients receiving antihypertensive drug therapy.

Children studied by ABPM included 35 patients with primary hypertension and 51 patients with secondary hypertension. Five children in the primary hypertension group and 6 children in the secondary hypertension group were studied twice, giving a total of 97 studies as mentioned above. Diagnoses among the patients with secondary hypertension included glomerulonephritis in 12 patients, solid organ transplant (renal or hepatic) in 11 patients, reflux nephropathy in 10 patients, renovascular hypertension in 5 patients, obstructive uropathy in 5 patients, polycystic kidney disease in 4 patients, and other causes in 4 patients.

Clinical characteristics of the children studied by ABPM are displayed in Table 1. Mean patient ages were similar in the primary and secondary hypertension groups. Anthropometric measurements at the time of ABPM were available for 77 patients (33 children with primary hypertension and 44 children with secondary hypertension). Children with primary hypertension were heavier and taller than children with secondary hypertension, and had significantly greater absolute body mass index (BMI) and BMI percentile.9


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  		TABLE 1. Clinical Characteristics at the Time of ABPM

 
ABPM was generally well-tolerated by all patients. For all 97 studies combined, the mean time studied by ABPM was 24.9 ± 3.7 hours. During this time period, a mean of 58 ± 10 readings were obtained per study; 85 ± 11% of attempted readings were successful.

Comparison of ABPM Results
As seen in Table 2, for studies performed in treated and untreated patients combined, children with secondary hypertension were found to have significantly higher diastolic BP loads during both the daytime and nocturnal portions of the ABPM studies and also a significantly greater nocturnal systolic BP load, compared with children with primary hypertension. Separate analysis of the studies obtained in untreated patients only is presented in Table 3. Although the differences were less significant than those for all patients combined, patients with secondary hypertension clearly had greater daytime diastolic and nocturnal systolic BP loads than children with primary hypertension, and a trend toward a greater nocturnal diastolic BP load.


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  		TABLE 2. Comparison of BP Loads in Children With Primary and Secondary Hypertension

 

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  		TABLE 3. Comparison of BP Loads in Children With Primary and Secondary Hypertension — Studies in Untreated Patients Only

 
Examination of the relationship between BP load and the likelihood of secondary hypertension in untreated patients is summarized in Table 4. Based on the distribution of BP loads in the study population, cutoff values of 25%, 30%, and 50% for daytime diastolic BP load and 40%, 50%, and 60% for nocturnal systolic BP load were tested as potential thresholds for the prediction of secondary hypertension. The most significant thresholds were found to be 25% for daytime diastolic load and 50% for nocturnal systolic load. In other words, secondary hypertension was significantly more likely than primary hypertension if the daytime diastolic BP load was ≥ 25% or the nocturnal systolic BP load was ≥50%. Secondary hypertension was also significantly more likely than primary hypertension if both of these findings were present (likelihood ratio = 5.0). This combination of findings had a sensitivity of 40% and specificity of 92% for the prediction of secondary hypertension (Table 4).


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  		TABLE 4. Likelihood of Secondary Hypertension With an Elevated BP Load for Untreated Patients

 
Comparison of dipping status is displayed in Table 5. For all patients combined, the magnitude of the nocturnal BP dip in children with secondary hypertension for both systolic and diastolic BP was significantly lower than that in children with primary hypertension. However, this difference was not present when the analysis of dipping status was restricted to untreated patients only (Table 5).


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  		TABLE 5. Comparison of Dipping Status

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
Although APBM has been validated in numerous pediatric studies and demonstrated to be an accurate, reproducible, and well-tolerated technique in children, its use has not been endorsed by consensus bodies,4 and no widely accepted indications for its use in the routine evaluation of pediatric hypertension have yet emerged.8,10 As a result, physicians who are called on to evaluate children with either suspected or known hypertension must base their evaluation and management of such children on casual BP readings, usually obtained in the office setting. As has been emphasized elsewhere, such BP readings in children are typically subject to many sources of error, and may not, therefore, be the most accurate means by which to evaluate hypertensive patients.8,11

In this study, we reviewed our experience with ABPM in the routine evaluation and management of childhood hypertension to determine whether ABPM could be used to differentiate between children with primary and secondary hypertension. The results of this study demonstrate that children with secondary hypertension manifest greater diastolic BP elevation than children with primary hypertension. This effect was seen in both the daytime and nocturnal portions of ABPM. In addition, children with secondary hypertension had significantly greater nocturnal systolic BP loads than children with primary hypertension. ABPM studies with the combination of an elevated daytime diastolic BP load and elevated nocturnal systolic BP load were highly specific for detecting patients with secondary hypertension.

The higher nocturnal BP loads in the children with secondary hypertension suggest that these children might have blunted nocturnal BP dips compared with children with primary hypertension. Although initial analysis of all 97 ABPM studies seemed to support this hypothesis, this finding was not seen when the analysis was restricted to untreated patients. Given that blunted nocturnal dipping has been seen in adults with secondary hypertension,5,12 and in hypertensive pediatric renal transplant recipients,13 it is likely that the failure of our data to support this hypothesis was a function of the relatively small number of untreated patients studied. Repetition of this study in a larger number of patients will be needed to definitively establish whether or not blunted dipping is a characteristic of children with secondary hypertension.

The results of this study indicate that ABPM could be useful as part of the initial evaluation of children newly referred for evaluation of hypertension. Such children, if found to have significant daytime diastolic and nocturnal systolic BP evaluation by ABPM, would then be identified as likely to have secondary hypertension. These children should then undergo a detailed diagnostic evaluation for possible renal disease or other secondary causes of hypertension. Conversely, children who had isolated systolic BP evaluation by ABPM, especially if present only during the daytime portion of the monitoring, could be assumed to be unlikely to have secondary hypertension, and, thus, could be spared a detailed and expensive diagnostic evaluation. Children with indeterminate findings on ABPM could perhaps be followed closely and restudied.

A second indication for ABPM in children would be to identify those children at greatest risk of end-organ damage related to hypertension. Studies in adults have clearly demonstrated that patients with nocturnal hypertension are at significantly greater risk of developing left ventricular hypertrophy and other manifestations of hypertension-induced end-organ damage.14,15 Although the relationship between ABPM findings and hypertensive end-organ effects has not been as firmly established for children as it has for adults, several recent studies have suggested that such a link may, indeed, be present for children.16–18 Therefore, children found to have significant nocturnal hypertension by ABPM would be candidates for echocardiography and other studies to evaluate for the presence of suspected end-organ damage.

The major limitations of this study are its single-center, retrospective design and the relatively small number of untreated patients studied by ABPM. However, the fact that ABPM was not routinely used to classify children as having either secondary or primary hypertension makes selection bias unlikely. And although the number of patients was relatively small, the detection of significant differences even in this small a population is highly suggestive that such differences actually exist and should be confirmed by a prospective, multicenter study involving greater numbers of children. Such a study would also be able to reexamine the "dipping" issue and determine whether the threshold values for BP load reported here are the most clinically useful ones, or whether other thresholds should be used.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
We have demonstrated that ABPM findings in children with secondary and primary forms of hypertension differ, with secondary hypertension being characterized by diastolic BP evaluation during the day and both systolic and diastolic BP elevation at night. These findings point to a potential indication for ABPM in the routine evaluation and management of children with hypertension, specifically identifying those children likely to have secondary hypertension and/or those children likely to have hypertension-induced end-organ damage.


   FOOTNOTES
 
Received for publication Jun 19, 2001; Accepted Jan 22, 2002.

Reprint requests to (J.T.F.), Pediatric Nephrology, Montefiore Medical Center, 111 E 210th St, Bronx, NY 10467. E-mail: jflynn{at}montefiore.org

Presented in abstract form at the Pediatric Academic Societies Meeting, Boston, MA, May 12, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. National High Blood Pressure Education Program Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children—1987. Pediatrics.1987; 79 :1 –25[Abstract/Free Full Text]
  2. Bartosh SM, Aronson AJ. Childhood hypertension: an update on etiology, diagnosis and treatment. Pediatr Clin N Am.1999; 46 :235 –252[CrossRef][ISI][Medline]
  3. Flynn JT. Evaluation and management of hypertension in childhood. Prog Pediatr Cardiol.2001; 12 :177 –188[CrossRef][Medline]
  4. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. 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. Pediatrics.1996; 98 :649 –658[Abstract/Free Full Text]
  5. Baumgart P, Walger P, Dorst KG, von Eiff M, Rahn KH, Vetter H. Can secondary hypertension be identified by twenty-four-hour ambulatory pressure monitoring? J Hypertens.1989; 7 :S25 –S28[CrossRef]
  6. Polonia J, Santos AR, Gama GM, Barros H. Accuracy of twenty-four-hour ambulatory blood pressure monitoring (night-day values) for the diagnosis of secondary hypertension. J Hypertens.1995; 13 :1738 –1741[ISI][Medline]
  7. Flynn JT. Impact of ambulatory blood pressure monitoring on the management of hypertension in children. Blood Press Monit.2000; 5 :211 –216[CrossRef][ISI][Medline]
  8. Portman RJ, Yetman RJ. Clinical uses of ambulatory blood pressure monitoring. Pediatr Nephrol.1994; 8 :367 –376[CrossRef][ISI][Medline]
  9. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC Growth Charts: United States. Hyattsville, MD: National Center for Heath Statistics; 2000
  10. Alpert BS, Daniels SR. Twenty-four-hour ambulatory blood pressure monitoring: now that technology has come of age—we need to catch up. J Pediatr.1997; 130 :167 –169[ISI][Medline]
  11. Koch VH, Colli A, Saito MI, et al. Comparison between casual blood pressure and ambulatory blood pressure monitoring parameters in healthy and hypertensive adolescents. Blood Press Monit.2000; 5 :281 –289[CrossRef][ISI][Medline]
  12. Middeke M, Klüglich M, Holzgrave H. Circadian blood pressure rhythm in primary and secondary hypertension. Chronobiology Int.1991; 8 :451 –459[ISI][Medline]
  13. Lingens N, Dobos E, Witte K, et al. Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation. Pediatr Nephrol.1997; 11 :23 –26[CrossRef][ISI][Medline]
  14. Giaconi S, Levanti C, Fommei E, et al. Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension. Am J Hypertens.1989; 2 :259 –261[ISI][Medline]
  15. Verdecchia P, Schillaci G. Prognostic value of ambulatory blood pressure monitoring. In: White WB, ed. Blood Pressure Monitoring in Cardiovascular Medicine and Therapeutics. Totowa, NJ: Humana Press, Inc; 2001:191–218
  16. 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][ISI][Medline]
  17. Harshfield GA, Pulliam DA, Alpert BS. Ambulatory blood pressure and renal function in healthy children and adolescents. Am J Hypertens.1994; 7 :282 –285[ISI][Medline]
  18. Sorof JM, Mielke TR, Portman RJ. Ambulatory blood pressure monitoring data are correlated with LV mass index and predictive of LV hypertrophy in children with hypertension [abstract]. Am J Hypertens.2000; 13 :39A
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics



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