Actu Padiatv Scund 68: 193-198, 1979

A SURVEY O F 164 FINNISH CHILDREN AND ADOLESCENTS WITH HYPERTENSION M. UHARI and 0. KOSKIMIES From the Department ojPuediutrics, Uni\*ersity of Onln und Children's Hospitul, University of'HelsinLi, Finiund

ABSTRACT. Uhari, M. and Koskimies, 0. (Department of Paediatrics, University of Oulu and Children's Hospital, University of Helsinki). A survey of 164 Finnish children and adolescents with hypertension. Acta Paediatr Scand, 68: 193, 1979.-A retrospective analysis was performed on 164 children and adolescents with persistent hypertension. Among the unselected 115 patients with hypertension seen within the last three years 47 (41 9%) exhibited renal disease, 37 (32%) coarctation of the aorta, 10 (9%) miscellaneous associated causes and 21 (18%) no associated cause (essential hypertension). A substantial number, 53/164, had a primary disease potentially curable by surgery, and in 37 patients the blood pressure was normalized postoperatively. The outcome depended mostly on the basic disease and the availability of chronic hemodialysis. 11/164 children have died, all because of terminal basic disease, and one with simultaneous hypertensive crisis. We thus recommend a thorough investigation in the case of a child with persistent hypertension.

KEY WORDS: Children, adolescents, hypertension, blood pressure

In most published series severe hypertension in childhood is found to be mainly secondary in nature, most often due to renal diseases or coarctation of the aorta (4, 17, 20). Gill et al. suggest that essential hypertension is rare in children, finding only one case in their series of 100 British children with hypertension (4). Little information is available from other paediatric centres in Europe, but in the United States the prevalence of essential hypertension has been found to be in general higher (1, 5, 12, IS), even up to 95% in one series of mildly hypertensive children (14). We present here a retrospective analysis of 164 hypertensive children and adolescents examined and followed up in two University Hospitals in Finland. The purpose was to find out the main causes of hypertension in childhood and the percentage of children with no detectable primary cause of their hypertension. PATIENTS AND METHODS Patients. The study wab based on a total of 164 children

with hypertension who had been treated and followed up

in the Department of Paediatrics. University of Oulu and in the Children's Hospital, University of Helsinki. 1 I5 of these children had visited the hospitals during the period 1973-1975, and the remaining 49 had been diagnosed and followed up earlier. Criteriu .for hypertension. The following criteria were used for inclusion: a diastolic pressure of 90 mmHg or more, or a systolic pressure of 130 mmHg or more in children under 5 years, or a systolic pressure of 140 mmHg or more in older children, all measured repeatedly over 3 months or more. These values are well above those published for normal Finnish children (18). The authors are aware that many infants and children with mild or labile hypertension or deficient follow-up are excluded under these criteria (14). Investigutions performed. The type of investigation was related to the initial clinical evaluation or diagnosis. If necessary one or more of the following examinations were carried out: aortography, renal angiography, cardiac catheterization, renal vein renin samples, or renal biopsy. Before making the final diagnosis of essential hypertension the primary causes of hypertension were excluded by renal function studies, urine analyses for bacteria, ECG, chest roentgenogram, intravenous urography, hormone estimations and in some cases renal angiography and renin estimations (2).

RESULTS The age distribution of the 164 patients, 63 girls and 101 boys, is seen in Fig. 1. The mean blood pressure recorded was 163/107 mmHg. Artu Paedicrtr S c a d 68

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M . Uhari and 0. Koskimies

Number of patients

0 Boys H Cirls

Age [years)

Fig. 1. Distribution of the 164 hypertensive children by sex and age at the time of the survey.

Reusons ,for referrul. 48 of the children had been referred to hospitals because of elevated blood pressure, including 17 who were symptomless and were identified at routine screening in a Child Welfare Centre o r in a school health examination. The other children had symptoms including cardiac murmur, proteinUna, urinary tract infection o r cardiac insufficiency (Table 1). Cuuses of hypertension. The numerical and percentage distributions of the conditions associated with hypertension in the patients followed up during the period 1960-1975 are depicted in Table 2. Since cardiological patients could not be identified accurately from ‘the earlier years, as seen in Table 2, the patients examined during the years 1973-1975 are thus documented separately. The most common cause of hypertension in these 115 cases was found to be renal disease. Chronic glomerular disease was found in 12 children, four with primary and eight with secondary glomerular disease. The latter ones had the following main diagnoses: three patients had anaphylactoid purpura, three had collagen disease, one had hydrocephalus and shunt-nephritis and one had Alport’s syndrome. In the category of pyelonephritis, seven patients had moderate to severe vesicoureteral reflux (Grades 111-V) and two had no reflux at all at the time when hypertension

was discovered (6). The diagnosis of pyelonephritis was based on repeated positive urine culture results and pathological findings at intravenous urography , voiding cystography, renal angiography or renal biopsy. One child had interstitial nephritis due to prolonged phenacetin ingestion. The earlier part of the series included one boy with interstitial nephritis due to hypercalcemia from vitamin D overdosage. One of the patients listed under “nephropathia” had renal biopsy changes that were not clearly classifiable and another had longstanding juvenile diabetes mellitus with renal damage. Renal damage developed in one patient during the induction treatment for leukaemia. One of the two patients with nephroblastoma was first detected due to a hypertensive crisis, while the other developed hypertension at the age of 15, having been in good health for ten years after the treatment of the primary tumour and metastases in the lung with surgery and radiotherapy. Coarctation of the aorta was the most frequently observed single condition causing hypertension being present in a total of 37 children (32%). Three patients also had a vascular lesion, severe arteriosclerosis and systolic hypertension. These cases are reported elsewhere (8). Table 1. Main clinical symptoms or signs leading to admission of the hypertensive children Symptom or sign High blood pressure with other symptom Cardiac murmur Proteinuria High blood pressure without other symptom Urinary tract infection Cardiac insufficiency Hematuria Headache Convulsions Anemia Growth retardation Others (palpable tumour, renal insuff. etc.) Total

No. of patients 31

21 18 17 17 11 8

7 6 4 3

21 164

Hypestension in children and adolescrnts

I95

Table 2. Diagnoses associatrd with hypertension b y agr groups Only patient5 followed up during the years 1973-1975 are representative for calculating the percentage distribution of the causes of hypertension

I . Patients followed up during 1973-1975 Diagnoris Renal disease Chronic glomerular disease Pyelonephritis With reflux Without reflux Obstructive uropathy Polycystic kidneys Renovascular disease Dysplastic kidneys Nephronophthisis Nephropathia Interstitial nephritis Hemolytic-uremic syndrome Coarctation of the aorta Arteriosclerosis juvenilis Turner’s syndrome Phaeochromoc ytoma Nephroblastoma Leukaemia (renal damage) Pseudoh ypoparath yreosis Obesity Essential hypertension Obvious Suspected

Number of patients by age groups: 0-5 5-10 10-16 Total (5%) 47 (41 5%) 1

4

9

1 1

83

-7

1 I

14

13

1 1

1

1 10 1 1 I

1

39 3

37 (32%) 2 2 I 1

I

I 1

9 7

1

1

2 21 (18%) 12 9 1 15

Table 3. Outcome in 164 hypertensive patients followed up f o r 1-17 years (mean 4 years)

Total

36 15 6

2

The total of 164 patients contained 13 in which no reason could be found for the elevated blood pressure, renal arteriography being normal. These patients fulfilled the criteria of essential hypertension (2). A further 14 patients were suspected to have essential

Cured (no longer receiving treatment) By operation Weight loss Under medication Under observation Dead (one after transplantation) Successful renal transplantation Hemodialysis after unsuccessful transplantation Hemodialysis (and medication) Not known

12

Total

4 1 3 1

Total

Outcome

7

11. Other patients

No. of patients

37 I 57 43 II 6 3 2 4 164

6

2 27

49

I64

hypertension, since no obvious primary disease was detected, but as renal artenography had not been performed the diagnosis could not be established with certainty. Eight of these children had labile hypertension, with their blood pressure elevated for three months or more, but recorded as normal on some occasions afterwards. Essential hypertension occurred in 21 (18%) of the 115 patients. Obesity was the only finding in two children with hypertension. Treatment and outcome. The follow-up time varied from one year to 17 years, with a mean of 4 years. 59 children received continuous medical treatment and 43 were followed-up untreated (Table 3). The latter included 6 with coarctation of the aorta waiting for an operation at the time of compiling the data. Diuretics were the most common antihypertensive preparation used, and methyldopa, reserpin, clonidine and hydralazine were also used. The A < t o PriidLitr S1 rim168

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M . Uhari and 0. Koskimies

Table 4. Types and outcome of surgical intervention in 64 hypertensive children Diagnobis

Operation

Coarctation of the aorta Unilateral renal disease Reflux nephropathy Phdeochromoc ytoma Renovascular disease

Reconstruction Nephrectomy Antireflux operation Extirpation of tumour Arterial reconstruction Nephrectomy Transplantation Resection of urethral valve Removal of the shunt

Renal insufficiency Obstructive uropathy Shunt-nephritis Total

medical treatment was effective in all cases of essential hypertension. A total of 64 patients had been operated upon, mainly for reconstruction of the aorta (Table 4). Out of the total of 164 children the blood pressure of 38 was completely normalized, 37 after surgical treatment and one after losing weight (Table 3). Ten children underwent renal transplantation, of which there were four rejected. There were eight children with hypertensive crisis which were successfully treated. Nine children died during the follow-up because of a renal disease (Table 3), the primary disease being pyelonephritis in three of these cases and glomerular disease in the others. Hypertension became worse in these cases as renal insufficiency advanced. One child died of nephroblastoma and hypertensive crisis and one of those with severe arteriosclerosis died during the follow-up period.

DISCUSSION Hypertension is an important factor when considering morbidity and mortality in adults, and it is a cause of disease and even death in childhood and infancy (11, 13, 17). Childhood hypertension and blood pressure are of interest because of the possibility that they may be markers of future vascular complications (1, 22). It has been claimed that childhood hyperten-

No. of patients

BP normalized in

35

26 6

6

5 3 2 I 10

2 2 I

1 1 64

37

sion is not so rare, as it has been found to occur with a prevalence of 1.4-8.2% in children and adolescents (3, 12, 15). Of course hypertension can be defined in quite different ways, e.g. statistically (those individuals exceeding the mean by 2 S.D. or more) or by empirically determined numerical blood pressure values, e.g. 140/90 mmHg. Thus the prevalences quoted are not always comparable (7). Our material was selective from this point of view and no prevalence figure can be calculated. The measurement of blood pressure as a routine part of the physical examination does not yet seem to work well in Finland, since only approximately every fourth child had his/ her blood pressure measured by the primary care physician before referral to hospital. Even so, 17 children had been referred precisely because their blood pressure was found to be high in routine health screening. The same etiological factors can cause hypertension in children and adults (16, 171, but most authors claim that the possibilities of finding a curable cause for the hypertension are clearly greater in children than in adults (4). This has been challenged by some, however (14). Our series, although somewhat selective, clearly showed that in properly investigated patients secondary hypertension was found in more than 80% of all hypertensive children and adolescents. The most common cause of hypertension in younger patients was coarctation of the aorta

Hypertension in children and adolescents (Table 2 ) . The proportion of cases with renal disease was greater among the older children. This is understandable, as patients with coarctation are cured early, whereas most acquired glomerular diseases first develop at school age and need time to progress before the appearance of hypertension. Pyelonephritis was associated with hypertension in 9 (8%) of the 115 patients. If hypertension is caused by pyelonephritis and vesicoureteral reflux there should be renal damage present (13). However, Schapiro demonstrated experimentally in rats that hypertension can increase the suspectibility to pyelonephritis (19). It is possible that our two cases of pyelonephritis without renal damage first had hypertension and later developed pyelonephritis. Although renal disease and coarctation of the aorta were the main causes of hypertension, essential hypertension was identified in 18% of our patients. It is probable that the proportion of essential hypertension would be greater in an epidemiological study (1, 10, 21). This contrasts with the results of Gill et al., whose study represented highly selected cardiac and renal patients with an even higher mean blood pressure (4). The outcome for children with hypertension depends first of all on the basic disease (20). Patients with hypertension due to an incurable disease fare better when the hypertension is controlled using antihypertensive medication, and even renal function might improve (9). The attitude of paediatricians to the treatment of hypertension has been conservative, which explains our finding that 43 patients with obvious hypertension were placed under observation without treatment. All the children who died during the follow-up period suffered from severe incurable disease, but as in the other cases, their hypertension could be kept under control by medication or surgical intervention. Since 53 out of the 164 patients had surgically curable disease, coarctation, renovascular disease or unilateral renal disease, patients with hypertension should be thoroughly 13-782872

197

investigated. Thus we completely disagree with authors who advocate a passive attitude to the examination of children with hypertension (14). The even more difficult and still unsolved question is how to screen for hypertension in children and particularly in infants. The best available screening method would include the routine measurement of blood pressure, careful palpation of femoral pulses and urine analysis, all of which should be a part of a normal child welfare examination. ACKNOWLEDGEMENT Financial support to this study was obtained from the Sigrid Juselius Foundation, Finland.

REFERENCES 1. Aschinberg, L. C., Zeis, P. M., Miller, R . A., John, E. G. & Chan, L.: Essential hypertension in child-

hood. J A M A , 238: 322, 1977. 2. Barrat, T. M.: Hypertension in childhood. In D. Williams (ed.): Urology in childhood, Encyclopedia of Urology, Suppl. XV. Springer-Verlag, New York 1974, p. 34. 3. Cassimos, C. H., Varlamis, G . , KaI'dmperiS, S. & Katsouyannopoulos, V.: Blood pressure in children and adolescents. Acta Paediatr Scund, 66: 439, 1977. 4. Gill, D. G . , daCosta, B. M., Cameron, J. S., Joseph, M. C., Ogg, C. S. & Chantler, C.: Analysis of 100 children with severe and persistent hypertension. Arch Dis Child, 51:951, 1976. 5 . Haggerty, R. J., Maroney, M. W. & Nadas, A . S.: Essential hypertension in infancy and childhood: Differential diagnosis and therapy. A m J Dis Child, 92: 535, 1956. 6. Heikel. P.-E. & Parkkulainen. K. V . : Vesico-ureteric reflux in children. A classification and results of conservative treatment. Ann Radiol, 9: 1, 1966. 7. Julius, S.: Classification of hypertension. In J. Genest, E . Koiw, & 0. Kuchel (eds.): Hypertension. McGraw-Hill, New York 1977, p. 9. 8. Kaitila, I . , Rapola, J., Selonen, A,, Lappalainen, J. & Joki, T.: A new type of severe arteriosclerosis beginning in childhood. Symposium on clinical genetics, Oslo 1977. 9. Kincaid-Smith, P.: Renal disease and hypertension. Med Clin North A m , 61: 61 1 , 1977. 10. Lieberman, E.: Essential hypertension in children and youth: A pediatric perspective. J Pediatr, 85: I , 1974. I I . Ljungqvist, A. & Wallgren, G.: Unilateral renal artery stenosis and fatal arterial hypertension in a newborn infant. Acru Paediatr Scand, 51: 575, 1962. 12. Loggie, J. M. H.: Prevalence of hypertension and distribution of causes. In M . I . New & L. S. Levine

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(eds.): Juvenile hypertension, Kroc Foundation series, vol. 8. Raven Press, New York 1977, p. I . 13. Loggie, J . M.: Systemic hypertension in children and adolescents. Causes and treatment. Pediatr Clin North A m , 18: 1273, 1971. 14. Londe, S . , Goldring, D., Gollub, S . W. & Hernandez, A,: Blood pressure and hypertension in children: Studies, problems, and perspectives. In M. I. New, & L. S . Levine (eds.): Juvenile hypertension, Kroc Foundation series, vol. 8. Raven Press, New York 1977, p. 13. 15. Masland, R., Heald, F., Goodale, W. & Gallagher, J.: Hypertensive vascular disease in adolescence. N e w Engl J M e d , 255: 894, 1956. 16. Pickering, G.: Hypertension. Causes, consequences and management. Churchill Livingstone, Edinburgh 1974. 17. Rance, C. P., Arbus, G. S . , Balfe, J. W. & Kooh, S. W.: Persistent systemic hypertension in infants and children. Pediatr CIin North A m , 2 1 ; 801, 1974.

18. Rasanen, L., Ahlstrom, A. & Kantero, R.-L.: Nutrition survey of Finnish rural children. Ann A c a d Scient Fennicue, A : V , Medicu, 168: 1, 1975. 19. Shapiro, A,: Experimental pyelonephritis and hypertension. Implications for the clinical problem. Ann Int M e d , 59: 37, 1963. 20. Still, J. L., & Cottom, D.: Severe hypertension in childhood. Arch Dis Child. 49: 313, 1974. 21. Uhari, M.: Unpublished data. 22. Zinner, S . H., Martin, L. F., Sacks, F., Rosner, B. & Kass, E.: A longitudinal study of blood pressure in childhood. A m J Epid, 100: 431, 1975. Submitted April 6, 1978 Accepted Aug. 24, 1978 ( M . U.) Department of Paediatrics University of Oulu 90220 Oulu 22 Finland

A survey of 164 Finnish children and adolescents with hypertension.

Actu Padiatv Scund 68: 193-198, 1979 A SURVEY O F 164 FINNISH CHILDREN AND ADOLESCENTS WITH HYPERTENSION M. UHARI and 0. KOSKIMIES From the Departmen...
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