| |
|
|
| Year : 1999 | Volume
: 10
| Issue : 3 | Page : 313-324 |
|
| Hypertension in Children |
|
|
CDA Goonasekera1, MJ Dillon2
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 |
 Introduction | |  |
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 | | |
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 | | |
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 | | |
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 | | |
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 | | |
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 | | |
| 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.  [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. |
| 3. | Uhari M. Changes in blood pressure during the first year of life. Acta Paediatr Scand 1980;69:613-7. [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. |
| 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. |
| 6. | Hohn AR. Diagnosis and management of hypertension in childhood. Pediatr Ann 1997;26:105-10. [PUBMED] |
| 7. | Daniels SR. Consultation with the specialist. The diagnosis of hypertension in children: an update. Pediatr Rev 1997; 1 8: 131-5. |
| 8. | Lieberman E. Essential hypertension in children and youth: a pediatric perspective. J Pediatr 1974;85:1-11. [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. [PUBMED] |
| 10. | Sinaiko AR. Treatment of hypertension in children. Pediatr Nephro! 1994;8:603-9. |
| 11. | Still JL, Cottom D. Severe hypertension in childhood. Arch Dis Child 1967;42:34-9. [PUBMED] |
| 12. | Deal JE, Snell MF, Barratt TM, Dillon MJ. Renovascular disease in childhood. J Pediatr 1992; 121:378-84. [PUBMED] |
| 13. | Scheinman JI, Crevi DL, Narla LD, Chan JC. Asymptomatic childhood hypertension. Nephron 1998;79:131-6. [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. |
| 15. | Leumann EP. Blood pressure and hypertension in childhood and adolescence. Ergeb Inn Med Kinderheilkd 1979;43:109-83. [PUBMED] |
| 16. | Fivush B, Neu A, Furth S. Acute hypertensive crises in children: emergencies and urgencies. Curr Opin Pediatr 1997;9:233-6. [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. |
| 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. |
| 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. |
| 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. [PUBMED] |
| 21. | Watson AR, Balfe JW, Hardy BE. Renovascular hypertension in childhood: achanging perspective in management. J Pediatr 1985; 106:366-72. [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. |
| 23. | Dillon MJ. The diagnosis of renovascular disease. Pediatr Nephrol 1997;11:366-72. [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. [PUBMED] |
| 25. | Dillon MJ, Shah V, Barratt TM. Renalvein renin measurements in children with hypertension. Br Med J 1978;2:168-70. [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. |
| 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. [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. [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. [PUBMED] |
| 30. | Stackpole RH, Melicow MM, Uson AC. Pheochromocytoma in children. J Pediatr1963;63:315-30. |
| 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. |
| 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. [PUBMED] |
| 33. | Rodd CJ, Sockalosky JJ. Endocrine causes of hypertension in children. Pediatr Clin North Am 1993;40:149-64. [PUBMED] |
| 34. | Gordon RD, Klemm SA, Tunny TJ, Stowasser M. Primary aldosteronism: hypertension with a genetic basis. Lancet 1992;-340:159-61. [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. |
| 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. |
| 37. | Dluhy RG, Lifton RP. Glucocorticoidremediable aldosteronism. Endocrinol Metab Clin North Am 1994;23:285-297. [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. |
| 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. [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. [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. [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. |
| 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. [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. |
| 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. [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. [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. [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. [PUBMED] |
| 49. | Gordon RD. Syndrome of hypertension and hyperkalemia with normal glomerular filtration rate. Hypertension 1986;8:93-102. [PUBMED] |
| 50. | Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992;71:169-80. [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. [PUBMED] [FULLTEXT] |
| 52. | Kaplan NM. Management of hypertensive emergencies. Lancet 1994;344:1335-8. [PUBMED] |
| 53. | Deal JE, Barratt TM, Dillon MJ. Management of hypertensive emergencies. Arch. Dis Child 1992;67:1089-92. |
| 54. | Pickering TG. The ninth Sir George Pickering memorial lecture. Ambulatory monitoring and the definition of hypertension. J Hypertens 1992; 10:401-9. |
| 55. | Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Porcellati C. Prognostic significance of the white coat effect. Hypertension 1997;29:1218-24. [PUBMED] [FULLTEXT] |
| 56. | Bloch A. Is white-coat hypertension a disease? Schweiz Rundsch Med Prax 1997; 86:6-8. [PUBMED] |
| 57. | Julius S, Mejia A, Jones K, et al. 'White coat' versus 'sustained' borderline hypertension in Tecumseh, Michigan. Hypertension 1990;16:617-23. [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 [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. |
| 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. [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. |
| 62. | Pickering GW. High blood pressure. London: J & A Churchill Ltd, 1955. |
| 63. | Coca A. Circadian rhythm and blood pressure control: physiological and pathophysiological factors. J Hypertens Suppl 1994;12:S13-21. |
| 64. | Zanchetti A, Mancia G. Blood pressure and organ damage. J Cardiovasc Pharmacol 1987;10(Suppl 6):S111-8. |
| 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. |
| 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. |
| 67. | Zanchetti A. Twenty-four-hour ambulatory blood pressure evaluation of antihypertensive agents. J Hypertens Suppl 1997;15: S21-5. |
| 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. |
| 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. |
| 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. |
| 71. | Parati G, Ulian L, Santucciu C, et al. Clinical value of blood pressure variability. Blood Press Suppl 1997;2:91-6. |
| 72. | Palatini P, Julius S. Heart rate and the cardiovascular risk. J Hypertens 1997; 15:3-17. |
| 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. |
| 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. |
| 75. | Sleight P. The importance of theautonomic nervous system in health and disease. Aust NZJ Med 1997;27:467-73. |
| 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. |
| 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. |
| 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. |
Correspondence Address:
CDA Goonasekera
Faculty of Medicine, University of Peradeniya, Peradeniya
Sri Lanka
  | Check |
PMID: 18212441 
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3] |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 4303 | | | Printed | 71 | | | Emailed | 0 | | | PDF Downloaded | 475 | | | Comments | [Add] | | |
|
|
