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The Significance of High Blood-pressure
LEADING
81
ARTICLES
is sustained at a high level, while the more is associated with a labile and intermittent hypertension, which may manifest itself under the stress of medical examination. For life assurance, only a single estimation of blood-pressure is usually made, and the resulting failure to distinguish between sustained hypertension and a labile bloodpressure reacts unfairly on many individuals. Yet it is difficult to see a solution, since the subsequent course of a labile blood-pressure is unpredictable. There is considerable evidence that the natural " " history of hypertonia and true hypertension are not so clearly distinguishable as Dr. EvArrs suggests. In his own series, cardiac pain was present in almost half of the 50 older patients placed in the hypertonia group, and 9 died with cardiac infarction. The younger patients in this category-recruits
ponent,
benign
THE LANCET LONDON:
The
SATURDAY, JULY 13,
1957
Significance of High Blood-pressure
IN recent years the problem of hypertension has been attacked with increasing vigour from many sides; but despite searching clinical, statistical, and experimental studies we are still unable to foretell with any certainty the results of increased bloodpressure in the individual patient. In the half-century since ALLBUTT first showed that hypertension could occur in the absence of renal disease the chief advances have been the recognition and separation of specific causes and forms of high blood-pressure. In particular, malignant hypertension has been defined as a fulminating disorder which may complicate any of the hypertensive diseases. Endocrine causes, such as Cushing’s syndrome and phaeochromocytoma of the adrenal medulla, are now clearly separated, and coarctation of the aorta is readily diagnosed. Chronic pyelonephritis and other less obvious forms of renal disease, sometimes affecting only one kidney, are regularly considered and occasionally discovered as the cause of hypertension. Nevertheless, these refinements of diagnosis are side-issues compared to the main problem, which concerns the significance of high’ blood-pressure in that great majority of patients who remain in the category of essential hypertension. As ALLBUTT made clear, this disorder is compatible with long life and freedom from serious disease ; on the other hand, its complications may cause sudden death or lifelong invalidism. This dilemma of prognosis carries unfortunate social implications, for the blood-pressure is becoming an important factor in acceptance for life assurance and superannuation benefits, and indeed for entry into many occupations. In our present issue this problem is forcibly stated hy Dr. WILLIAM EvArrs, who has long made a study of high blood-pressure and its manifestations in people of various ages. His thesis is that in both the young and the old high blood-pressure may follow a benign course for many years without giving rise to cardiovascular complications. This he would term "hypertonia as distinct from true arterial hypertension," which he associates with cardiovascular hypertrophy and which carries a grave prognosis, owing particularly to cardiac and cerebral arterial disease. This thesis is a restatement of the longrecognised fact that the serious manifestations of high blood-pressure are due to arterial degeneration, which is accelerated and aggravated by increased arterial strain. The crucial question is : Why do some patients with high blood-pressure develop arterial degeneration-whether this be the acute arteriolar necrosis of malignant hypertension, or the slowly evolving atheroma of so-called benign hypertension-whereas others do not ? Clinical observation indicates (and Dr. EVANS’s findings support this view) that cardiovascular hypertrophy and degeneration develop predominantly in patients whose blood-pressure, particularly the diastolic com"
"
course
"
"
for National Service-showed no evidence of cardiovascular disease after a ten-year follow-up, but a further period of observation is necessary before the development of sustained hypertension and its vascular complications can be excluded. An investigation of this kind by LEVY et all provided definite support for such a sequence of events. From examination of the medical records of more than 22,000 U.S. army officers over a period of from one to twenty-five years, they obtained evidence that sustained hypertension was commoner in those with previous transient hypertension than in those who have shown no previous elevation of blood-pressure. The rates of retirement and death from cardiovascular renal disease were also consistently higher among those with transient hypertension than in those without. A transition from intermittent to sustained hypertension is often seen in chronic renal disease. Recent clinical observations have provided contributory evidence of a different kind. In many hypertensive disorders it has been found that the blood-pressure may remain increased after the original cause has been removed. This may happen in patients with phæochromocytoma, Cushing’s syndrome, coarctation of the aorta, or unilateral renal disease. Thus various forms of acute hypertension may give rise to sustained hypertension, the mechanism of which is different from that of the early phase. It seems justifiable to presume that
a similar relationship may hold for the early and late stages of essential hypertension. The mechanism which sustains chronic hypertension That this mechanism is generalised is obscure. organic narrowing of the arteries is unlikely for several reasons, not the least of which is that if such changes are partly attributable to the severity and duration of the hypertension, as there is good reason to believe, they can hardly be named as the cause of the change from an intermittent to a sustained level. It is essential, therefore, in assessing prognosis to keep an open mind about the relation between different grades of essential hypertension. While cardiovascular hypertrophy is directly proportional to the mechanical stresses produced by increased arterial pressure, degenerative changes in the heart and blood-vessels depend also on other factors, some of them metabolic, and for this reason atheroma shows an individual variation independent of the blood-
1. Levy, R. L., Hillman, C. C., med. Ass. 1944, 126, 829.
Stroud, W. D., White, P. D. J. Amer.
82
pressure level. The most striking example of this is the higher prevalence of vascular degenerative complications in men than in women with the same degree of hypertension. Many workers are investigating the aetiological aspects of atheroma, and until these are more clearly understood we should be in no hurry to accept new concepts or to change the terminology. Meanwhile practice would be improved and much injustice avoided if those who use the sphygmomanometer in routine medical examinations were to give more thought to the significance of a high bloodpressure reading. The distinction should at least be made between sustained hypertension and a temporary aberration from the normal. This can be readily done by repeated estimations, either in the course of a day or over a longer time, in conditions as free as possible from physical and emotional disturbance. In addition a search should always be made for the clinical and cardiographic signs which differentiate hypertensive cardiovacular disease from simple
hypertension.
Amyotonia Congenita THE infant with severe hypotonia and impaired movement of the limbs and often reduction of the tendon reflexes presents a difficult problem in diagnosis and prognosis. In 1900 OPPENHEIMdescribed briefly under the name of myatonia congenita infants who were severely hypotonic with reduced spontaneous movements but no actual muscle paralysis and with weakened or absent tendon-jerks. He suggested that this disorder was due to defective development of the muscles or of the peripheral motor neurones and that improvement occurred in the course of time. This condition, which became known as Oppenheim’s disease or amyotonia congenita, has been the subject of controversy as to whether it is in fact a pathological entity. It soon became clear that many infants who were severely hypotonic in the first few weeks or months of life rapidly became worse and died, showing at necropsy degenerative changes in the anterior horn cells similar to those found in the infantile spinal muscular atrophy which had been described by WERDNIG2 and by HOFFMANN.3 In other infants, however, who early in life had shown a similar clinical picture of gross hypotonia the clinical course and the pathological findings were different. SILVESTRI4 described 2 children with the clinical picture of amyotonia congenita in infancy in whom there was a family history of an aunt with progressive muscular dystrophy. When the elder of the affected children reached the age of 16 the hypotonia had disappeared, but he had the characteristic proximalmuscle wasting and weakness of the Erb type of progressive muscular dystrophy. BATTEN 56 maintained that the picture of amyotonia congenita could be caused by myopathy without involvement of the central or peripheral nervous system, and in 1914 SPILLER7 concluded that the clinical picture oj amyotonia congenita as described by OPPENHEIM could be caused by several different pathological 1. 2. 3. 4. 5. 6. 7.
Oppenheim, H. Mschr. Psychiat. Neurol. 1900, 8, 232. Werdnig, G. Arch. Psychiat. 1891, 22, 437. Hoffmann, J. Dtsch. Z. Nervenkr. 1893, 10, 292. Silvestri, T. Gazz. Osp. Milano, 1909, 30, 577. Batten, F. E. Quart. J. Med. 1909, 3, 313. Batten, F. E. Proc. R. Soc. Med. (Sect. Neurol.) 1914, 8, 69. Spiller, W. G. Brain, 1914, 36, 75.
SPILLER’S views have been confirmed
by subsequent studies. Although in the majority of affected infants who died changes in the anterior-horn cells resembled those of the Werdnig-HoHmann disease,8several carefully studied cases showed no pathological lesions in the spinal cord.’ 0-13 ALDREN TURNER 14 followed up a family of Batten’s patients in which 5 members had shown. the typical picture of amyotonia congenita in infancy, and in adult life no hypotonia but localised wasting and weakness of certain muscles, especially the sternomastoids and shoulder-girdle muscles. The disorder appeared to be non-progressive, and on clinical grounds ALDREN TURNER suggested that it was a congenital myopathy. This was subsequently con.firmed 15 when 1 of the patients died of bacterial endocarditis and no abnormality was found in the central nervous system on thorough examination, while sections of affected muscles showed changes resembling those in myopathic
processes.
muscles. In the past few years follow-up studies of children who showed the clinical syndrome of amyotonia congenita in infancy have been carried out in Denmark by BRANDT 16 17 and in England by WALTON.18-20 BRANDT studied 131 children who had muscular hypotonia and weakness beginning at birth or in the first year of life. He found that 87 probably had progressive spinal muscular atrophy (WerdnigHoffmann), and in 28 the hypotonia was symptomatic of various conditions such as mental deficiency, cerebral diplegia, or nutritional or metabolic disorders such as rickets. There were 13 other patients, of whom 6 recovered apparently completely, 3 improved strikingly, 3 improved but remained disabled, and 1 died of pneumonia after improving somewhat. BRANDT thought that these cases were a heterogeneous group, but that at least 3 resembled the congenital nonprogressive myopathy originally described by BATTEN. WALTON’s series was of 109 patients in whom amyotonia congenita had been diagnosed in early childhood. The follow-up showed that 67 had infantile spinal muscular atrophy of which the prognosis was bad; 55 died between the ages of 5 weeks and 12 years, while the 12 survivors were all severely disabled, the eldest being aged 20. There were 3 cases of progressive muscular dystrophy and 1 of polymyositis, and in 20 cases the hypotonia was symptomatic of various conditions such as mental deficiency and cerebral diplegia. (Infantile polyneuritis as a cause of the syndrome, although not encountered by WALTON, has been recorded.21) The remaining 17 patients in WALTON’S series were of particular importance. They were all limp, floppy children who showed considerable delay in reaching the milestones indicating increasing muscular activity ; but as they got older they all improved, 8 recovering completely between the ages of 5 and 15 years. In the other 9 the hypotonia gradually 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
Greenfield, J. De Lange, C.
G., Stern, R. O. Ibid, 1927, 50, 652. Acta pœdiat., Stockh. 1937, 20, suppl. 3. Councilman, T., Dunn, C. H. Amer. J. Dis. Child. 1911, 2, 340. Haushalter, P. Arch. Méd. Enf. 1920, 23, 133. Silberberg, M. Virchows Arch. 1923, 242, 42. Menges, O. Dtsch. Z. Nervenheilk. 1931, 121, 240. Aldren Turner, J. W. Brain, 1940, 63, 163. Aldren Turner, J. W. Ibid, 1949, 72, 25. Brandt, S. J. Child Psychiat. 1948, 1, 266. Brandt, S. Werdnig-Hoffmann’s Infantile Progressive Muscular Atrophy. Copenhagen, 1950. Walton, J. N. Lancet, 1956, i, 1023. Walton, J. N. Proc. R. Soc. Med. 1957, 50, 301. Walton, J. N. J. Neurol. Neurosurg. Psychiat. 1957, 20, 144. Chambers, R., MacDermot, V. Lancet, 1957, i, 397.
81
ARTICLES
is sustained at a high level, while the more is associated with a labile and intermittent hypertension, which may manifest itself under the stress of medical examination. For life assurance, only a single estimation of blood-pressure is usually made, and the resulting failure to distinguish between sustained hypertension and a labile bloodpressure reacts unfairly on many individuals. Yet it is difficult to see a solution, since the subsequent course of a labile blood-pressure is unpredictable. There is considerable evidence that the natural " " history of hypertonia and true hypertension are not so clearly distinguishable as Dr. EvArrs suggests. In his own series, cardiac pain was present in almost half of the 50 older patients placed in the hypertonia group, and 9 died with cardiac infarction. The younger patients in this category-recruits
ponent,
benign
THE LANCET LONDON:
The
SATURDAY, JULY 13,
1957
Significance of High Blood-pressure
IN recent years the problem of hypertension has been attacked with increasing vigour from many sides; but despite searching clinical, statistical, and experimental studies we are still unable to foretell with any certainty the results of increased bloodpressure in the individual patient. In the half-century since ALLBUTT first showed that hypertension could occur in the absence of renal disease the chief advances have been the recognition and separation of specific causes and forms of high blood-pressure. In particular, malignant hypertension has been defined as a fulminating disorder which may complicate any of the hypertensive diseases. Endocrine causes, such as Cushing’s syndrome and phaeochromocytoma of the adrenal medulla, are now clearly separated, and coarctation of the aorta is readily diagnosed. Chronic pyelonephritis and other less obvious forms of renal disease, sometimes affecting only one kidney, are regularly considered and occasionally discovered as the cause of hypertension. Nevertheless, these refinements of diagnosis are side-issues compared to the main problem, which concerns the significance of high’ blood-pressure in that great majority of patients who remain in the category of essential hypertension. As ALLBUTT made clear, this disorder is compatible with long life and freedom from serious disease ; on the other hand, its complications may cause sudden death or lifelong invalidism. This dilemma of prognosis carries unfortunate social implications, for the blood-pressure is becoming an important factor in acceptance for life assurance and superannuation benefits, and indeed for entry into many occupations. In our present issue this problem is forcibly stated hy Dr. WILLIAM EvArrs, who has long made a study of high blood-pressure and its manifestations in people of various ages. His thesis is that in both the young and the old high blood-pressure may follow a benign course for many years without giving rise to cardiovascular complications. This he would term "hypertonia as distinct from true arterial hypertension," which he associates with cardiovascular hypertrophy and which carries a grave prognosis, owing particularly to cardiac and cerebral arterial disease. This thesis is a restatement of the longrecognised fact that the serious manifestations of high blood-pressure are due to arterial degeneration, which is accelerated and aggravated by increased arterial strain. The crucial question is : Why do some patients with high blood-pressure develop arterial degeneration-whether this be the acute arteriolar necrosis of malignant hypertension, or the slowly evolving atheroma of so-called benign hypertension-whereas others do not ? Clinical observation indicates (and Dr. EVANS’s findings support this view) that cardiovascular hypertrophy and degeneration develop predominantly in patients whose blood-pressure, particularly the diastolic com"
"
course
"
"
for National Service-showed no evidence of cardiovascular disease after a ten-year follow-up, but a further period of observation is necessary before the development of sustained hypertension and its vascular complications can be excluded. An investigation of this kind by LEVY et all provided definite support for such a sequence of events. From examination of the medical records of more than 22,000 U.S. army officers over a period of from one to twenty-five years, they obtained evidence that sustained hypertension was commoner in those with previous transient hypertension than in those who have shown no previous elevation of blood-pressure. The rates of retirement and death from cardiovascular renal disease were also consistently higher among those with transient hypertension than in those without. A transition from intermittent to sustained hypertension is often seen in chronic renal disease. Recent clinical observations have provided contributory evidence of a different kind. In many hypertensive disorders it has been found that the blood-pressure may remain increased after the original cause has been removed. This may happen in patients with phæochromocytoma, Cushing’s syndrome, coarctation of the aorta, or unilateral renal disease. Thus various forms of acute hypertension may give rise to sustained hypertension, the mechanism of which is different from that of the early phase. It seems justifiable to presume that
a similar relationship may hold for the early and late stages of essential hypertension. The mechanism which sustains chronic hypertension That this mechanism is generalised is obscure. organic narrowing of the arteries is unlikely for several reasons, not the least of which is that if such changes are partly attributable to the severity and duration of the hypertension, as there is good reason to believe, they can hardly be named as the cause of the change from an intermittent to a sustained level. It is essential, therefore, in assessing prognosis to keep an open mind about the relation between different grades of essential hypertension. While cardiovascular hypertrophy is directly proportional to the mechanical stresses produced by increased arterial pressure, degenerative changes in the heart and blood-vessels depend also on other factors, some of them metabolic, and for this reason atheroma shows an individual variation independent of the blood-
1. Levy, R. L., Hillman, C. C., med. Ass. 1944, 126, 829.
Stroud, W. D., White, P. D. J. Amer.
82
pressure level. The most striking example of this is the higher prevalence of vascular degenerative complications in men than in women with the same degree of hypertension. Many workers are investigating the aetiological aspects of atheroma, and until these are more clearly understood we should be in no hurry to accept new concepts or to change the terminology. Meanwhile practice would be improved and much injustice avoided if those who use the sphygmomanometer in routine medical examinations were to give more thought to the significance of a high bloodpressure reading. The distinction should at least be made between sustained hypertension and a temporary aberration from the normal. This can be readily done by repeated estimations, either in the course of a day or over a longer time, in conditions as free as possible from physical and emotional disturbance. In addition a search should always be made for the clinical and cardiographic signs which differentiate hypertensive cardiovacular disease from simple
hypertension.
Amyotonia Congenita THE infant with severe hypotonia and impaired movement of the limbs and often reduction of the tendon reflexes presents a difficult problem in diagnosis and prognosis. In 1900 OPPENHEIMdescribed briefly under the name of myatonia congenita infants who were severely hypotonic with reduced spontaneous movements but no actual muscle paralysis and with weakened or absent tendon-jerks. He suggested that this disorder was due to defective development of the muscles or of the peripheral motor neurones and that improvement occurred in the course of time. This condition, which became known as Oppenheim’s disease or amyotonia congenita, has been the subject of controversy as to whether it is in fact a pathological entity. It soon became clear that many infants who were severely hypotonic in the first few weeks or months of life rapidly became worse and died, showing at necropsy degenerative changes in the anterior horn cells similar to those found in the infantile spinal muscular atrophy which had been described by WERDNIG2 and by HOFFMANN.3 In other infants, however, who early in life had shown a similar clinical picture of gross hypotonia the clinical course and the pathological findings were different. SILVESTRI4 described 2 children with the clinical picture of amyotonia congenita in infancy in whom there was a family history of an aunt with progressive muscular dystrophy. When the elder of the affected children reached the age of 16 the hypotonia had disappeared, but he had the characteristic proximalmuscle wasting and weakness of the Erb type of progressive muscular dystrophy. BATTEN 56 maintained that the picture of amyotonia congenita could be caused by myopathy without involvement of the central or peripheral nervous system, and in 1914 SPILLER7 concluded that the clinical picture oj amyotonia congenita as described by OPPENHEIM could be caused by several different pathological 1. 2. 3. 4. 5. 6. 7.
Oppenheim, H. Mschr. Psychiat. Neurol. 1900, 8, 232. Werdnig, G. Arch. Psychiat. 1891, 22, 437. Hoffmann, J. Dtsch. Z. Nervenkr. 1893, 10, 292. Silvestri, T. Gazz. Osp. Milano, 1909, 30, 577. Batten, F. E. Quart. J. Med. 1909, 3, 313. Batten, F. E. Proc. R. Soc. Med. (Sect. Neurol.) 1914, 8, 69. Spiller, W. G. Brain, 1914, 36, 75.
SPILLER’S views have been confirmed
by subsequent studies. Although in the majority of affected infants who died changes in the anterior-horn cells resembled those of the Werdnig-HoHmann disease,8several carefully studied cases showed no pathological lesions in the spinal cord.’ 0-13 ALDREN TURNER 14 followed up a family of Batten’s patients in which 5 members had shown. the typical picture of amyotonia congenita in infancy, and in adult life no hypotonia but localised wasting and weakness of certain muscles, especially the sternomastoids and shoulder-girdle muscles. The disorder appeared to be non-progressive, and on clinical grounds ALDREN TURNER suggested that it was a congenital myopathy. This was subsequently con.firmed 15 when 1 of the patients died of bacterial endocarditis and no abnormality was found in the central nervous system on thorough examination, while sections of affected muscles showed changes resembling those in myopathic
processes.
muscles. In the past few years follow-up studies of children who showed the clinical syndrome of amyotonia congenita in infancy have been carried out in Denmark by BRANDT 16 17 and in England by WALTON.18-20 BRANDT studied 131 children who had muscular hypotonia and weakness beginning at birth or in the first year of life. He found that 87 probably had progressive spinal muscular atrophy (WerdnigHoffmann), and in 28 the hypotonia was symptomatic of various conditions such as mental deficiency, cerebral diplegia, or nutritional or metabolic disorders such as rickets. There were 13 other patients, of whom 6 recovered apparently completely, 3 improved strikingly, 3 improved but remained disabled, and 1 died of pneumonia after improving somewhat. BRANDT thought that these cases were a heterogeneous group, but that at least 3 resembled the congenital nonprogressive myopathy originally described by BATTEN. WALTON’s series was of 109 patients in whom amyotonia congenita had been diagnosed in early childhood. The follow-up showed that 67 had infantile spinal muscular atrophy of which the prognosis was bad; 55 died between the ages of 5 weeks and 12 years, while the 12 survivors were all severely disabled, the eldest being aged 20. There were 3 cases of progressive muscular dystrophy and 1 of polymyositis, and in 20 cases the hypotonia was symptomatic of various conditions such as mental deficiency and cerebral diplegia. (Infantile polyneuritis as a cause of the syndrome, although not encountered by WALTON, has been recorded.21) The remaining 17 patients in WALTON’S series were of particular importance. They were all limp, floppy children who showed considerable delay in reaching the milestones indicating increasing muscular activity ; but as they got older they all improved, 8 recovering completely between the ages of 5 and 15 years. In the other 9 the hypotonia gradually 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
Greenfield, J. De Lange, C.
G., Stern, R. O. Ibid, 1927, 50, 652. Acta pœdiat., Stockh. 1937, 20, suppl. 3. Councilman, T., Dunn, C. H. Amer. J. Dis. Child. 1911, 2, 340. Haushalter, P. Arch. Méd. Enf. 1920, 23, 133. Silberberg, M. Virchows Arch. 1923, 242, 42. Menges, O. Dtsch. Z. Nervenheilk. 1931, 121, 240. Aldren Turner, J. W. Brain, 1940, 63, 163. Aldren Turner, J. W. Ibid, 1949, 72, 25. Brandt, S. J. Child Psychiat. 1948, 1, 266. Brandt, S. Werdnig-Hoffmann’s Infantile Progressive Muscular Atrophy. Copenhagen, 1950. Walton, J. N. Lancet, 1956, i, 1023. Walton, J. N. Proc. R. Soc. Med. 1957, 50, 301. Walton, J. N. J. Neurol. Neurosurg. Psychiat. 1957, 20, 144. Chambers, R., MacDermot, V. Lancet, 1957, i, 397.