Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 8854 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

ARTICLE Table of Contents   
Year : 1999  |  Volume : 10  |  Issue : 3  |  Page : 313-324
Hypertension in Children


1 Faculty of Medicine, University of Peradeniya, Sri Lanka
2 Nephrology, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom

Click here for correspondence address and email
 

How to cite this article:
Goonasekera C, Dillon M J. Hypertension in Children. Saudi J Kidney Dis Transpl 1999;10:313-24

How to cite this URL:
Goonasekera C, Dillon M J. Hypertension in Children. Saudi J Kidney Dis Transpl [serial online] 1999 [cited 2020 Aug 4];10:313-24. Available from: http://www.sjkdt.org/text.asp?1999/10/3/313/37239

   Introduction Top


Blood pressure increases with growth, particularly during neonatal period and puberty. [1],[2],[3],[4] Therefore, interpretation of blood pressure in children involves the use of nomograms, unlike in adults, where a preset figure such as 140/90 mmHg is used to identify hypertension.

As recommend by the 1977 and 1987 task forces, a child is considered hypertensive if his or her office blood pressure is above 95th centile for age. [4],[5] Thus, recognition of hypertension in children is based on an arbitrary epidemiological threshold5 and not a pathological definition. This may have contributed to the estimated 2-3% preva­lence of hypertension in children. Most children diagnosed as hypertensives are post-pubertal and considered as 'essential' hypertensives.

They have only a mild increase in blood pressure, which may have little adverse effect until adult life. [6] It is usually treated by weight reduction, exercise, and low salt diet before any pharmacological intervention. [7],[8],[9],[10] However, there is a small minority of children, often younger with much higher blood pressures, who suffer from secondary hypertension. Hypertension in this group of children is associated with high morbidity and mortality in the short-term and usually requires urgent treatment. [11] This review is mostly dedicated to the management of the latter group of children.


   Presentation Top


Many children with hypertension are symptomatic at presentation, but a signify cant number of children, with severe hyper­tension, are incidentally diagnosed on routine examination. [12],[13] The presenting features vary widely with age. [14] During infancy more than half of the patients present with cardiac failure and almost one third with respiratory distress. [15] Irritability and failure to thrive are also not uncommon features. During childhood, headache, nausea, vomiting, tiredness, and facial palsy are common. [15] Hypertensive encephalopathy and coma have been reported in 10% of cases at presentation. [15]

An infant in cardiac failure may appear to be normotensive at presentation although the original cause for illness is high blood pressure. Therefore, it is not unusual to misdiagnose some cases initially as children with cardiomyopathy [Figure - 1].

Some children may present in a hyper­tensive crisis, a state in which acute management of the elevated blood pressure is important for a favourable outcome. [16] Such crisis includes hypertensive encephalopathy (a medical emergency in which cerebral mal­function is attributed to the severe elevation of blood pressure) and accelerated hyperten­sion (a clinical syndrome characterised by marked elevation of blood pressure with acute arteriolar injury).

In children, high blood pressure may be an associated feature of systemic disease. For example, renovascular hypertension may be a result of neurofibromatosis type 1, idiopathic hypercalcemia, Marian's syndrome, Takayasu disease, systemic vasculitis and other rare syndromes. [17]

Untreated hypertension may result in progressive tissue damage, especially of vital organs such as heart, kidney, brain and eye. The clinical consequences range from heart failure and pulmonary oedema to stroke and renal failure. Pressure overload has been blamed for the onset of these complications but the actual mechanisms are yet to be understood.


   Etiology Top


The prevalence of secondary hypertension in children is approximately 0.1%, similar to that of juvenile diabetes mellitus. [15],[16],[17],[18] Most of the underlying diseases are rare and a relatively small number of conditions are responsible for the hypertension in over 90% of patients. [19] The majority (60-70%) have been found to have renal abnor­malities. Reflux nephropathy and obstructive uropathy are the commonest abnormallities. [19],[20] Renovascular hypertension, resulting from a lesion or lesions that impair blood flow, constitutes 5-25% of cases and is often due to fibromuscular dysplasia. [21],[22],[23]

In subjects with a renal abnormality or renovascular disease contributing to the onset of hypertension, raised plasma renin has been a relatively frequent finding. [24] A renal vein renin ratio (RVR) of 1.5 and above has been considered significant evidence for lateralisation and a favourable indication for a surgical approach.[12],[23],[24],[25],[26],[27] However, some patients have benefited from angioplasty and even nephrectomy (especially if the kidney was severely damaged and apparently nonfunctioning) in the absence of a lateralizing RVR. In the event of renovascular disease contributing to hypertension, it must be realised that, in children, the vessel disease is often bilateral (70% of cases) and also may involve small vessels of the kidney that are not amenable to surgery or angioplasty. [12]

Renal imaging is another routine necessity in these cases. Renal ultra sound in experienced hands is a good preliminary investigation that will provide many clues to the aetiology; for example, renal size, texture, drainage, blood flow etc. The 99 TcDimer­captosuccinic acid (DMSA) scan detects the functional tubular mass, and is considered the best investigation that delineates 'renal scarring': [28],[29] a feature of reflux nephropathy. However, abnormal images indis­tinguishable from 'renal scarring' may also be seen in children with renovascular disease. Furthermore, reflux nephropathy and renovascular diseases are known to co­exist. Under these circumstances, a dynamic renal scan (such as DTP A or MAG3) may be useful for the assessment of renal blood flow, but occasionally could be misleading unless interpreted carefully. For example, equal renal function in a dynamic scan may not necessarily suggest that both kidneys have equal renal perfusion [Figure - 2].

Extra renal vascular disease such as coarctation of aorta contributes to 0.2-2% of the cases of hypertension. Long standing hypertension in coarctation of aorta may present as cardiomegaly and rib notching on chest x-ray. However, the latter is seldom seen nowadays as 2-D Echocardiography and other ultrasound techniques often make the diagnosis very early in life.

Pheochromocytomas occur in 0.2 - 2% of cases and although traditionally described as a cause of episodic hypertension, they cause sustained hypertension in many cases (88%).[30] One third of cases may also have extraadrenal (paragangliomas) or multiple tumours.[30] Usually the condition is spora­dic, but can be associated with multiple endocrine neoplasia type 2, [31] which is now known to be linked with an abnormality of protooncogene. [32]

Other adrenal abnormalities can lead to hypertension. Congenital adrenal hyperplasia (17 α-hydroxylase deficiency or 11β-hydro­xylase deficiency), an autosomal recessive disease, is usually associated with hyper­tension and hypokalemia. [33] It is character­rised by raised mineralocorticoid activity and suppressed peripheral renin activity.

Primary hyperaldosteronism can result from adrenal adenoma or hyperplasia, where raised plasma aldosterone and low plasma renin are associated with hypoka­lemia and hypertension. [34]

In another autosomal dominant disease, a fusion mutation of the 11-β hydroxylase and aldosterone synthatase results in the expression of aldosterone synthatase, in both zona glomerulosa and fasciculata, rendering them responsive to adrenocorticotropin (ACTH). [35],[36],[37] This results in inappropriate secretion of aldosterone and hyperaldosteronism. Treat­ment of these cases with dexamethasone leads to suppression of ACTH and, there­fore, improvement of hypertension. [38]

The clinical picture of hyperaldosteronism may also be seen in the absence of raised plasma aldosterone; a condition named 'apparent mineralocorticoid excess' (AME). [39] Several groups have demonstrated that the syndrome of AME is an autosomal recessive disorder resulting from inactivating mutations in the 11-β hydroxysteroid dehydrogenase type 2 enzyme (11-β-HSD2) gene. [40],[41],[42] This allows cortisol to access the mineral­ocorticoid receptor without being inactivated by the above enzyme at tissue level. Cortisol, therefore, exerts its full mineralocorticoid activity leading to apparent mineralocorticoid excess. It is effectively treatable with spironolactone. A similar clinical condition may be acquired with excessive intake of liquorice, which contains carbenexolone that inhibits 11 β-HSD2. [43]

Liddle's syndrome, [44] a rare familial condition presents with early severe hypertension, hypokalemia, suppressed renin and aldosterone, and responds to amiloride. It has recently been shown to be a consequence of (3 or y subunit mutations of the epithelial sodium channel, which increases the number of these channels in the apical membrane of the collecting tubular cells leading to excessive reabsorption of sodium and hypertension. [45],[46],[47]

A similar condition to Liddle's but with hyperkalemia and hyperchloremia and intact renal function has been described and named Gordon's syndrome. [48] The molecular basis for this condition is yet to be discovered. It is postulated that it is a result of a chloride shunt in the distal tubule preventing aldosterone from functioning as a kaluretic agent but allows excessive reabsorption of sodium and chloride with suppression of renin production. [49]

Other genetic abnormalities that may contribute to hypertension are being discovered with the rapid evolution of molecular biological techniques. The angio-tensinogen gene [50] and adducin gene [51] have been implicated in the generation of some forms of essential hypertension.


   Investigations and Management Top


In general, the sequelae of untreated hypertension depend on its severity, duration, and cause although serious complications may arise at a relatively low level of blood pressure (e.g. encephalopathy). The most frequent complications of severe childhood hypertension involve the central nervous System; hypertensive encepha­lopathy, facial palsy, visual impairment, cerebral infarction and hemorrhage. Cardiac decompensation and renal failure are also well-recognized sequelae of uncontrolled severe hypertension. Damage to other organs may also follow a similar course if hypertension is not treated.

The investigation of a hypertensive child is, therefore, aimed at the diagnosis of the underlying aetiology, assessment of target organ damage and recognition of immediate life threatening complications. Early inter­vention is known to be associated with a greater chance of reversibility of the damage that has occurred.

Symptomatic children at presentation and children with severe hypertension need urgent antihypertensive therapy awaiting the quest for the etiology. In the absence of symptoms, the decision to treat is made arbitrarily, based on the level of blood pressure. Some may present in emergency circumstances, which need urgent attention and careful monitoring. In a child with a hypertensive emergency, it is always important to recognise conditions that may mimic a hypertensive emergency; for example raised intra cranial pressure due to a space­occupying lesion. [52] History and clinical examination usually provide sufficient clues for differentiation.

It is recommended that some routine basic investigations [Table - 1] be undertaken in all children with hypertension before proceeding to special investigations [Table - 2]. In most cases, antihypertensive therapy is initiated before the investigations are completed.

We recommend the following manage­ment plan [Figure - 3] and [Figure - 4], taking into account the arbitrary nature of the definition of hypertension, recommendations of the task force4 and the geographical and other differences between blood pressure nomograms.

The objective of emergency treatment is prevention of hypertension related adverse events such as stroke, encephalopathy and other vital organ damage. Rapid reduction in blond pressure. However, may also precipitate adverse events and hence is contra­indicated.[10],[53] In hypertensive encephalo­pathy or accelerated hypertension, the blood pressure should be reduced very slowly aiming at a reduction of 1/3 of total planned reduction of blood pressure over the first 6­12 hours, 1/3 over 12-36 hours and 1/3 over 36-72 hours [Figure - 4]. The drugs of choice for this purpose are labetalolol or sodium nitroprusside, preferably with intraarterial pressure monitoring, although oral or sub­lingual nifedipine has been used. It is, how­ever, important that physicians be aware of the potential risk of sudden hypotension with the use of sublingual nifedipine that may be detrimental. Some authors also advocate use of esmolol, diazoxide, hydra­lazine, and minoxidil for emergency therapy. [10]

Once blood pressure is controlled and the presenting complications have improved, the second line of investigations may be undertaken to delineate the etiology of hypertension [Table - 2]. This will allow institution of a specific surgical or medical treatment.


   Uncertainties Top


White coat hypertension

Individuals who are hypertensive on visiting clinic but otherwise normotensive have been recognised and labelled as 'white coat hypertensives'. The prognosis in such subjects remains uncertain. [54],[55] Do these subjects need treatment? Some argue that white coat hypertension is a precursor of essential hypertension,[56],[57],[58] whereas others do not identify any increased risk of cardiovascular disease or target organ damage in this population. [55] It is now argued that this uncertainty may have resulted from a selection bias, where subjects in whom white coat effect improves with repeated measurements and have no added future cardiovascular risk were included in the group with persistent white coat effect and with evidence of target organ damage. [59] This suggest that children with white coat effect may need follow-up until such time when the white coat effect disappears or shows evidence of target organ damage that requires active treatment.

Adequacy of treatment

The goal of antihypertensive therapy is widely accepted as reduction of blood pressure to a level below the 95th percentile for age and sex. [10] This may not be the ideal target in some cases. For instance, in patients with fibromuscular dysplasia, where cranial vessels may also be involved, cerebral blood flow may be dependent on a higher blood pressure. In this case, reduction of blood pressure to normality may induce detrimental consequences such as cerebral infarction or even sudden death. In some cases of renovascular disease, the renal function may also deteriorate when blood pressure is normalised. It is, therefore, obvious that the degree of blood pressure reduction may have to be individualised in many pediatric cases with hypertension. Ideally, blood pressure should be reduced to a level that brings progressive target organ damage to a halt and reduces the future risk of cardiovascular complications. Currently, we have no index to evaluate this goal.

Blood Pressure measurement

It is important that we recognize the differences between various blood pressure measurement techniques, [60] even if the instrument used has been clinically validated. [61] Most nomograms currently in use have been developed using mercury sphygmomanometers and blood pressure measurements in clinic. Therefore, the blood pressure levels in children can be interpreted against such data only if obtained under similar circumstances.

Ambulatory Vs office blood pressure

Although the knowledge of a diurnal rhythm in blood pressure in not new, [62] this has not hitherto been taken into account in the interpretation of blood pressure. With technological advances, it is now possible to measure 24-hor blood pressure in children.

However, interpretation of 24-hour blood pressure in children is still in its early stage since defining the abnormal has been diffi­cult. Furthermore, ambulatory blood pres­sure, defined as a daytime- night time or 24-hour mean, does not adequately quantify fluctuations in blood pressure, which is a known risk factor. [63],[64] A lower mean blood pressure may not necessarily mean better control of blood pressure as this does not recognize the trough/peak ratio, a further index predicting the risk-benefit ratio of antihypertensive therapy.[65],[66],[67] The importance of assessing the variability (fluctuation) in blood pressure and pulse rate in the identification of subjects with increased cardiovascular risk has been recognised. [68],[69],[70],[71],[72],[73],[74],[75] .Such indices are not yet utilized quantitatively in the interpretation of ambulatory 24-hours blood pressure.

'Nocturnal dip' and 'white coat effect' can be considered as preliminary observations of blood pressure behavior. They still need clarification in order to understand their biological meaning.[76],[77],[78]


   Conclusion Top


The majority of hypertensive children have only a mild increase in blood pressure. A minority has a moderate to severe rise in blood pressure often with evidence of target organ damage that clearly needs urgent investigation and treatment. There is no clear cut-off point for recognition of hypertensive children. It is important for physicians to recognize the arbitrary nature of the definition of hypertension and the inevitable errors in blood pressure measurement techniques and, therefore, not base clinical decisions purely on the level of blood pressure.

 
   References Top

1.de Swiet M, Fayers P, Shinebourne EA. Systolic blood pressure in a population of infants in the first year of life: the Bromp­ton study. Pediatrics 1980;65:1028-35.  Back to cited text no. 1  [PUBMED]  
2.de Swiet M, Fayers P, Shinebourne EA. Blood pressure in first 10 years of life: the Brompton study. Br Med J 1992:304:23-6.  Back to cited text no. 2    
3.Uhari M. Changes in blood pressure during the first year of life. Acta Paediatr Scand 1980;69:613-7.  Back to cited text no. 3  [PUBMED]  
4.National Heart, Lung and Blood Institute, Bethesda, Maryland. Report of the second task force on blood pressure control in children- 1987. Pediatrics 1987;79:1-25.  Back to cited text no. 4    
5.Blumenthal S, Epps RP, Heavenrich R, et al. Report of the task force on blood pressure control in children. Pediatrics 1977; 59:1-11,797-820.  Back to cited text no. 5    
6.Hohn AR. Diagnosis and management of hypertension in childhood. Pediatr Ann 1997;26:105-10.  Back to cited text no. 6  [PUBMED]  
7.Daniels SR. Consultation with the specialist. The diagnosis of hypertension in children: an update. Pediatr Rev 1997; 1 8: 131-5.  Back to cited text no. 7    
8.Lieberman E. Essential hypertension in children and youth: a pediatric perspective. J Pediatr 1974;85:1-11.  Back to cited text no. 8  [PUBMED]  
9.Shear CL, Burke GL, Freedman DS, Berenson GS. Value of childhood blood pressure measurements and family history in predicting future blood pressure status Results from 8 years of follow-up in the Bogalusa Heart Study. Pediatrics 1986;77:862-9.  Back to cited text no. 9  [PUBMED]  
10.Sinaiko AR. Treatment of hypertension in children. Pediatr Nephro! 1994;8:603-9.  Back to cited text no. 10    
11.Still JL, Cottom D. Severe hypertension in childhood. Arch Dis Child 1967;42:34-9.  Back to cited text no. 11  [PUBMED]  
12.Deal JE, Snell MF, Barratt TM, Dillon MJ. Renovascular disease in childhood. J Pediatr 1992; 121:378-84.  Back to cited text no. 12  [PUBMED]  
13.Scheinman JI, Crevi DL, Narla LD, Chan JC. Asymptomatic childhood hypertension. Nephron 1998;79:131-6.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Dillon MJ. Clinical Aspects of Hypertension. In: Holliday MA, Barratt TM, Vernier RL, eds. Pediatric Nephrology.2nd ed. Baltimore: Williams & Wilkins1987:743-57.  Back to cited text no. 14    
15.Leumann EP. Blood pressure and hyper­tension in childhood and adolescence. Ergeb Inn Med Kinderheilkd 1979;43:109-83.  Back to cited text no. 15  [PUBMED]  
16.Fivush B, Neu A, Furth S. Acute hypertensive crises in children: emergencies and urgencies. Curr Opin Pediatr 1997;9:233-6.  Back to cited text no. 16  [PUBMED]  
17.Swinford RD, Ingelfinger JR. Evaluation of hypertension in childhood diseases. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology, 4th ed. Baltimore:Williams & Wilkins 1999:1007-­30.  Back to cited text no. 17    
18.Rames LK, Clarke WR, Conner WE, Reiter MA, Lauer RM. Normal blood pressure and the evaluation of sustained blood pressure elevation in childhood: the Muscatine study. Pediatrics 1978;61:245-51.  Back to cited text no. 18    
19.Wyszynska T, Cichocka E, Wieteska Klimczak A, Jobs K, Januszewicz P. A single pediatric center experience with 1025 children with hypertension. Acta Paediatr 1992;81:244-6.  Back to cited text no. 19    
20.Gill DG, Mendes de Costa B, Cameron JS, Joseph MC, Ogg CS, Chantler C. Analysis of 100 children with severe and persistent hypertension. Arch Dis Child 1976;51: 951-­6.  Back to cited text no. 20  [PUBMED]  
21.Watson AR, Balfe JW, Hardy BE. Renovascular hypertension in childhood: achanging perspective in management. J Pediatr 1985; 106:366-72.  Back to cited text no. 21  [PUBMED]  
22.Dillon MJ. Therapeutic strategies in renovascular hypertension. In: Proesmans W, ed. Therapeutic strategies in children with renal disease, London: Bailliere Tindall 1997:675-86.  Back to cited text no. 22    
23.Dillon MJ. The diagnosis of renovascular disease. Pediatr Nephrol 1997;11:366-72.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Savage JM, Dillon MJ, Shah V, Barratt TM, Williams DI. Renin and blood pressure in children with renal scarring and vesicoureteric reflux. Lancet 1978;2:441-4.  Back to cited text no. 24  [PUBMED]  
25.Dillon MJ, Shah V, Barratt TM. Renalvein renin measurements in children with hypertension. Br Med J 1978;2:168-70.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.Sonkodi S, Abraham G, Mohacsi G. Effects of nephrectomy on hypertension, renin activity and total renal function inpatients with chronic renal artery occlusion. I Hum Hvptens 1990;4:277-9.  Back to cited text no. 26    
27.Amsterdam EA, Couch NP, Christlieb AR, et al. Renal vein renin activity in the prognosis of surgery for renovascular hypertension. Am J Med 1969;47:860-8.  Back to cited text no. 27  [PUBMED]  
28.Verber IG, Strudley MR, Meller ST. 99mTc dimercaptosuccinic acid (DMSA) scan as first investigation of urinary tract infection. Arch Dis Child 1988;63:1320-5.  Back to cited text no. 28  [PUBMED]  
29.Smellie JM, Shaw PJ, Prescod NP, Bantock HM. 99mTc dimercaptosuccinicacid (DMSA) scan in patients with established radiological renal scarring. Arch Dis Child 1988;63:1315-9.  Back to cited text no. 29  [PUBMED]  
30.Stackpole RH, Melicow MM, Uson AC. Pheochromocytoma in children. J Pediatr1963;63:315-30.  Back to cited text no. 30    
31.Lairmore TC, Ball DW, Baylin SB, Wells SA Jr. Management of pheochromo­cytomas in patients with mutiple endocrine neoplasia type 2 syndormes. AnnSurg 1993;217:595-603.  Back to cited text no. 31    
32.Rodien P, Jeunemaitre X, Dumont C, Beldjord C, Plouin PF. Genetic alterations of the RET protooncogene in familial and sporadic pheochromocytomas. Horm Res 1997;47:263-8.  Back to cited text no. 32  [PUBMED]  
33.Rodd CJ, Sockalosky JJ. Endocrine causes of hypertension in children. Pediatr Clin North Am 1993;40:149-64.  Back to cited text no. 33  [PUBMED]  
34.Gordon RD, Klemm SA, Tunny TJ, Stowasser M. Primary aldosteronism: hypertension with a genetic basis. Lancet 1992;-340:159-61.  Back to cited text no. 34  [PUBMED]  
35.Lifton RP, Dluhy RG, Powers M, etai. Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase, Nat Genet 1992;2:66-74.  Back to cited text no. 35    
36.Lifton RP, Dluhy RG, Powers M, et al. A chimaeric 11 beta hydroxylase /aldosterone synthase gene causes glucocorticoidreme-diable aldosteronism and human hypertension. Nature 992; 355:262-5.  Back to cited text no. 36    
37.Dluhy RG, Lifton RP. Glucocorticoidremediable aldosteronism. Endocrinol Metab Clin North Am 1994;23:285-297.  Back to cited text no. 37  [PUBMED]  
38.Miyahara K, Kawamoto T, Mitsuuchi Y, et al. The chimeric gene linked to glucocorticoid-suppressible hyper­aldosteronism encodes a fused P-450 protein possessing aldosterone synthase activity. BiochemBiophys Res Commun 1992; 189:885-91.  Back to cited text no. 38    
39.Ulick S, Levine LS, Gunczler P, et al. A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. J Clin Endocrinol Metab 1979;49:757-64.  Back to cited text no. 39  [PUBMED]  
40.Wilson RC, Krozowski ZS, Li K, et al. A mutation in the HSD 11 beta 2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab 1995;80: 2263-8.  Back to cited text no. 40  [PUBMED]  [FULLTEXT]
41.Stewart PM, Krozowski ZS, Gupta A, et al. Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene. Lancet 1996;347: 88-91.  Back to cited text no. 41  [PUBMED]  
42.Mune T, Rogerson FM, Nikkila H, Agarwal AK, White PC. Human hypertension caused by mutations in the kidneyisozyme of 11 beta-hydroxysteroid dehydrogenase. Nat Genet 1995;10:394-9.  Back to cited text no. 42    
43.Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR. Mineralocorticoid activity of liquorice: 11­beta-hydroxysteroid dehydrogenase deficien­cy comes of age. Lancet 1987;2: 821-4.  Back to cited text no. 43  [PUBMED]  
44.Botero Velez M, Curtis JJ, Warnock DG. Brief report: Liddle's syndrome revisited a disorder of sodium reabsorption in the distal tubule. N Engl J Med 1994;330:178-81.  Back to cited text no. 44    
45.Snyder PM, Price MP, McDonald FJ, et al. Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel. Cell 1995; 83:969-78.  Back to cited text no. 45  [PUBMED]  [FULLTEXT]
46.Shimkets RA, Warnock DG, Bositis CM, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 1994;79:407-14.  Back to cited text no. 46  [PUBMED]  
47.Jeunemaitre X, Bassilana F, Persu A, et al. Genotype-phenotype analysis of a newly discovered family with Liddle's syndrome. J Hypertens 1997; 15:1091-100.  Back to cited text no. 47  [PUBMED]  [FULLTEXT]
48.Gordon RD, Geddes RA, Pawsey CG, O'Halloran MW. Hypertension and severe hyperkalaemia associated with suppression of renin and aldosterone and completely reversed by dietary sodium restriction. Australas Ann Med 1970; 19:287-94.  Back to cited text no. 48  [PUBMED]  
49.Gordon RD. Syndrome of hypertension and hyperkalemia with normal glomerular filtration rate. Hypertension 1986;8:93-102.  Back to cited text no. 49  [PUBMED]  
50.Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992;71:169-80.  Back to cited text no. 50  [PUBMED]  
51.Cusi D, Barlassina C, Azzani T, et al. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 1997;349:1353-7.  Back to cited text no. 51  [PUBMED]  [FULLTEXT]
52.Kaplan NM. Management of hypertensive emergencies. Lancet 1994;344:1335-8.  Back to cited text no. 52  [PUBMED]  
53.Deal JE, Barratt TM, Dillon MJ. Management of hypertensive emergencies. Arch. Dis Child 1992;67:1089-92.  Back to cited text no. 53    
54.Pickering TG. The ninth Sir George Pickering memorial lecture. Ambulatory monitoring and the definition of hypertension. J Hypertens 1992; 10:401-9.  Back to cited text no. 54    
55.Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Porcellati C. Prognostic significance of the white coat effect. Hypertension 1997;29:1218-24.  Back to cited text no. 55  [PUBMED]  [FULLTEXT]
56.Bloch A. Is white-coat hypertension a disease? Schweiz Rundsch Med Prax 1997; 86:6-8.  Back to cited text no. 56  [PUBMED]  
57.Julius S, Mejia A, Jones K, et al. 'White coat' versus 'sustained' borderline hypertension in Tecumseh, Michigan. Hypertension 1990;16:617-23.  Back to cited text no. 57  [PUBMED]  
58.Palatini P, Mormino P, Santonastaso M, et al. Target-organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study. Hypertension 1998;31: 57-63  Back to cited text no. 58  [PUBMED]  [FULLTEXT]
59.Palatini P, Dorigatti F, Roman E, et al. White-coat hypertension: a selection bias. Harvest Study Investigators. Hypertension and Ambulatory Recording Venetia Study. J Hypertens 1998; 16:977-84.  Back to cited text no. 59    
60.Goonasekera CD, Wade AM, Slattery M, Brennan E, Dillon MJ. Validation of new blood pressure monitors for children: Defects by default. Eur J Pediatr 1998; 157: 1035.  Back to cited text no. 60  [PUBMED]  [FULLTEXT]
61.O'Brien E, Petrie J, Littler W, et al. The British Hypertension Society protocol for the evaluation of blood pressure measuring devices. J Hypertens 1993;11:S43-S62.  Back to cited text no. 61    
62.Pickering GW. High blood pressure. London: J & A Churchill Ltd, 1955.  Back to cited text no. 62    
63.Coca A. Circadian rhythm and blood pressure control: physiological and patho­physiological factors. J Hypertens Suppl 1994;12:S13-21.  Back to cited text no. 63    
64.Zanchetti A, Mancia G. Blood pressure and organ damage. J Cardiovasc Pharmacol 1987;10(Suppl 6):S111-8.  Back to cited text no. 64    
65.Morgan T, Menard J, Brunner H. Trough to peak ratio as a guide to BP control: measurement and calculation. J Hum Hypertens 199 8; 12:49-53.  Back to cited text no. 65    
66.Morgan T, Menard J, Brunner H. Twentyfour hour blood pressure control and trough to peak ratio: who, when, how and why? J Hum Hypertens 1998; 12:45-8.  Back to cited text no. 66    
67.Zanchetti A. Twenty-four-hour ambulatory blood pressure evaluation of antihypertensive agents. J Hypertens Suppl 1997;15: S21-5.  Back to cited text no. 67    
68.Sokolow M, Werdegar D, Kain HK, Hinman AT. Relationship between level of blood pressure measured casually and by portable recorders and severity of complications in essential hypertension. Circulation 1966;34:279-98.  Back to cited text no. 68    
69.Feola M, Boffano GM, Procopio M, Reynaud S, Allemano P, Rizzi G. Ambulatory 24-hour blood pressure monitoring: correlation between blood pressure variability and left ventricular hypertrophy in untreated hypertensive patients. G Ital Cardiol 1998;28:38-44.  Back to cited text no. 69    
70.Pierdomenico SD, Bucci A, Costantini F, Lapenna D, Cuccurullo F, Mezzetti A. Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease. J Am Coll Cardiol 1998;31:1627-34.  Back to cited text no. 70    
71.Parati G, Ulian L, Santucciu C, et al. Clinical value of blood pressure varia­bility. Blood Press Suppl 1997;2:91-6.  Back to cited text no. 71    
72.Palatini P, Julius S. Heart rate and the cardiovascular risk. J Hypertens 1997; 15:3-17.  Back to cited text no. 72    
73.Mancia G, Di Rienzo M, Parati G. Variability of heart rate in hypertensive patients: clinical and physiopathological implications. Ann Ital Med Int 1994; 9Suppl:21S-6S.  Back to cited text no. 73    
74.Singh JP, Larson MG, Tsuji H, Evans JC,O'Donnell CJ, Levy D. Reduced heart rate variability and new-onset hypertension:insights into pathogenesis of hypertension: The Framingham Heart Study. Hypertension 1998;32:293-7.  Back to cited text no. 74    
75.Sleight P. The importance of theautonomic nervous system in health and disease. Aust NZJ Med 1997;27:467­-73.  Back to cited text no. 75    
76.Morfis L, Howes LG. Nocturnal fall in blood pressure in the elderly is related topresence of hypertension and not age. Blood Press 1997;6:274-8.  Back to cited text no. 76    
77.Ohkubo T, Imai Y, Tsuji I, et al. Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study. Am J Hypertens 1997; 10:1201-7.  Back to cited text no. 77    
78.Verdecchia P, Schillaci G, Borgioni C, et al. White coat hypertension and white coat effect. Similarities and differences. Am J Hypertens 1995;8:790-8.  Back to cited text no. 78    

Top
Correspondence Address:
CDA Goonasekera
Faculty of Medicine, University of Peradeniya, Peradeniya
Sri Lanka
Login to access the Email id


PMID: 18212441

Rights and Permissions


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Introduction
    Presentation
    Etiology
    Investigations a...
    Uncertainties
    Conclusion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed4095    
    Printed69    
    Emailed0    
    PDF Downloaded462    
    Comments [Add]    

Recommend this journal