American
Heart Journal
November, 1977, Volume 94, N u m b e r 5
Editorial Prevalence of primary and secondary hypertension Lars Wilhelmsen, M.D. G. Berglund, M.D. Goteborg, Sweden
It is well established that the risk of cerebrovascular and cardiovascular complications increases gradually with increasing blood pressure. It is also documented that t h e r e is a high prevalence of blood pressure increase to that level which clearly warrants treatment. 1-4 Thus, 10 to 15 per cent of middle-aged men and women in various countries seem to benefit from treatment. The proportion of the total hypertensive population with demonstrable causes of the hypertension is, however, not definitely known. In various textbooks and reviews the prevalence of secondary hypertension has been estimated to be I0 to 20 per cent. These figures have usually been based on studies in series of hospitalized patients, but there are several reasons t o suspect that the prevalence of secondary hypertension is overestimated in these selected groups of patients. It is important to establish the prevalence of secondary hypertension, since the investigations that are currently undertaken before treatment are largely aimed at detecting secondary forms of hypertension, in which the patients might be cured by specific treatment such as surgery. The diagnostic investigations are also aimed at detecting hypertensive heart complications and renal complications, as these findings have been shown to carry From the Section of Preventive Cardiology, Dept. of Medicine I, Sahlgrenska Hospital, G6teborg, Sweden. Received for publication March 3, 1977. Reprint requests: Lars Wilhelmsen, M.D., Physicfan-in-Chief~ Department of Medicine I, Sahlgrenska Hospital, S:413 45 G6teborg, Sweden.
November, 1977, Vol. 94, No. 5, pp. 543-546
a poorer prognosis, ~ calling for a closer supervision and more intensive treatment. The prevalence of secondary hypertension is certainly not the same in all countries of the world because of varying prevalence of the conditions leading to, for example, renal parenchymal damage, such as glomerulonephritis and pyelonephritis. A decreasing incidence of some of these conditions, such as analgesic nephropathy, is also to be expected. Several investigators have shown that a large part of the hypertensive individuals in different populations are unknown, and any measure aiming at detecting and treating the major part of the hypertensive individuals in a population would increase the cost of the medical services. In this situation it.is important to acquire information concerning the extent of examinations needed. A high prevalence of secondary, presumably curable, hypertension would warrant more extensive preliminary investigations as would a high frequency of patients with hypertensive organ damage. In a recent investigation ~ we have been able to estimate the prevalence of primary and secondary hypertension in middle-aged men in Sweden. Many of the economic and social circumstances as well as the disease panorama of this population is similar to that of several other countries. Thus, it is probable that these findings can be extrapolated to these other populations. The study population consisted of a randomly selected third of all men aged 47 to 54 years and
American Heart Journal
543
Wilhelmsen and Berglund
Table I. The prevalence of primary and secondary hypertension (n -- 686). The number of previously known cases are given with brackets
No. Renoparenchymaldisease Chronic glomerulonephritis Gouty nephropathy Renal tuberculosis Analgesic nephropathy Renal dysplasia Renovascular disease Aortic coarctation Primary ald0steronism Primary hyperparathyroidism Suspected but not proved unilateral hydronephrosis Primary hypertension
25
[ % 3.6
15 (15) 3 (1) 4 (4) 1 (1) 2 (1) 4 (1) 1 (1) 1 (1) 2 (1) 7 (2) 646
0.6 0.1 0.1 0.3 L0 94.2
who were residents of GSteborg, Sweden. These men belonged to the intervention group of a multifactor primary preventive trial2 Of those 9,996 men who were invited to the screening examination 7,455 (75 per cent) attended. It has been shown that the non-participants differed from the participants with respect to mortality and several social variables, but there were no indications that diseases leading to secondary hypertension were more common among the nonparticipants. 7 In the first run, those who were not receiving antihypertensive treatment and whose blood pressures were above 175 mm. Hg systolic blood pressure (SBP) or 115 mm. Hg diastolic blood pressure (DBP) were recalled within 2 weeks to have their blood pressures remeasured. Those who still had blood pressures above these limits and all those who were on antihypertensive treatment were examined for secondary hypertension. The screening methods and the investigations at the Hypertension Clinic have been reported in detail elsewhere?' The examinations of the hypertensive patients consisted of a careful clinical scrutinizing for possible secondary hypertension. The more complicated methods were performed in certain age groups-random samples of the total hypertensive group. The investigations included a complete physical examination with auscultation of the heart and lungs, palpation of the femoral arteries and peripheral pulses, examination of the occular fundi, and a battery of laboratory tests including
544
measurement of serum electrolytes and creatinine, urine test for albuminuria and urinary sediment, urine culture, and determination of renal concentration capacity with a 13-hour thirst test, and, if the latter result was abnormal, a vasopressin tannate test. Isotope renography was carried out in the 287 men born in 1915, 1916, 1920, and 1921 using a standard method and apparatus. Intravenous pyelography (in 52 men) and renal aortography (in 12 men) were also performed with standard methods according to special indications. Catecholamine concentrations were determined in all 58 men born in 1921 using a method described by von Euler and Floding.s On the basis of the results of these investigations and a thorough examination of each patient's c a s e records, a diagnosis was recorded using the criteria given below. Renoparenchymal disease 1. The diagnosis of chronic glomerulonephritis required persistent or intermittent albuminuria or hematuria, or both, without there being another cause of these abnormalities. 2. Renal tuberculosis was recorded when there was a history of pulmonary or renal tuberculosis, or both, with tubercle bacilli in the urine. 3. Gouty nephropathy was recorded in the presence of known arthritis urica and lowered concentration ability (vasopressin t a n n a t e test < 800 mmol./Kg. H20). 4. Renal dysplasia was defined as one small kidney without a history of urinary tract infections. A kidney was considered small if it was over 2 cm. shorter than the other kidney and less than 10 cm. in length with oddly-shaped or club-like calices on the intravenous pyelogram. '1 5. Phenacetin nephropathy was recorded in patients with a long-standing history of abuse, lowered urinary concentration ability, and signs of papillary necrosis on the intravenous pyelogram. 6. Chronic pyelonephritis required a history of recurrent urinary tract infections and a lowered urinary concentration ability. Renovascular disease Screening for renovascular disease was carried out by isotope renography.Patients with abnormal renograms were admitted to hospital for renal aortography and other investigations. Arteriographic verfication was required for a
November, 1977, Vol. 94, No. 5
Primary and secondary hypertension
diagnosis of renal artery stenosis or intrarenal occlusion. Abnormally high ipsilatera! renin secretion or normalization of the blood pressure after surgery was not required for this diagnosis. Isotope renography was als0 performed if there were clinical signs of renovascular disease-for example, abdominal murmurs, drug resistant Or accelerating hypertension, or increasing serum creatinine levels.
Primary aldosteronism A hospital-verified diagnosis was required. Patients with spontaneous hypokalemia or hypokalemia during diuretic treatment whose serum potassium levels did not become normal after Stopping treatment were admitted to hospital for investigation.
Primary hyperparathyroidism A hospital-verified diagnosis was required. Serum calcium and phosphorous were not routinely screened.
Phaochromocytoma A hospital-verified diagnosis was needed. Catecholamines in urine were determined only in men born in 1921. Of~the 7,455 men who were screened, 686 (9 per cent) had hypertension according to the abovementioned criteria. Of these 60 pe r cent were untreated, 23 per cent were treated b u t had blood pressure at screening above S B P 175 or D B P 115 mm. Hg, and only 17 per cent had an acceptable control of their blood pressure. The number and percentage of cases with various types of hypertension appears in Table I. In seven cases of hydronephrosis (two previously known and five newly detected) we could not determine whether or not the hypertension was caused by the hydronephrosis and the resulting partial obstruction to urinary flow. Three patients did not become normotensive after operation and needed continuing antihypertensive treatment, an.d four patients were not operated on because they became normotensive on drug treatment and there were no other indications for operation. Thus, a specific cause of hypertension was found or reasonably suspected in only 40 of the 686 patients (6 per cent). Eight patients had previously undergone surgical treatment, In only two cases did the patients investigation lead to surgical intervention, and both these patients
American Heart Journal
required antihypertensive treatment one year after' their operations, b u t lower doses were needed than before. 9 The methods of recognizing secondary hypertension were those normally used in clinical practice. Owing to the limited capacity of the laboratory, an isotope renogram was carried out only in four randomly selected age groups. In patients with hypertension refractory to treatment, investigation for renovascular causes was also carried out in the other age groups. Thus, most cases of renovascular hypertension amenable to surgical treatment were probably detected. Parenchymatous kidney disease without abnormal laboratory findings and with normal serum creatinine levels and concentration capacity may have been present without being detected. However, these patients had probably minor kidney damage, which in m o s t cases would not have been treated other than with hypotensive drugs even if discovered. Primary aldosteronism was probably excluded with a relatively high degree of certainty. Primary byperparathyroidism as a cause of hypertension may also have been present in more than the two cases who were found in our series since serum calcium was not measured routinely. Thus, the prevalence of secondary hypertension was lower in this study than according to other estimates. ~~ Our analysis is, however, the first one which has been performed in subjects derived from screening of a general population sample. Furthermore, we only studied men aged 47 to 54 years. The prevalence of secondary hypertension might be higher in women or in younger men. Our results suggest, however, that the risk of missing cases of secondary hypertension in middle-aged men is small and extensive investigations do not seem to be necessary in hypertensive subjects found at screening. In patients with hypertension referred to hospital, secondary hypertension is probably over-represented and more extensive routine investigations might be justified. Isotope renography as a screening instrument for renovascular hypertension cannot be recommended. The prevalence of renovascular hypertension was low, and there were many false positive renograms. TM Thus, our results support the bad cost-benefit ratio found in recent analyses of urography and isotope renography as screening instruments for renovascular hyperten-
545
Wilhelmsen and Berglund
sion, 15and of comparisons of surgical and medical treatment of renovascular hypertension. 16 Thus, the present data indicate t h a t the resources for
8.
management Of hypertension should be devoted more to case-finding and treatment t h a n to elabo, rate investigative measures.
REFERENCES
1. National Health Survey: H~pertension and hypertensive heart disease in adults, Washington, i966, Public Health Service PUblications. 2. BSb J., Humerfelt, S, and Wed,rvang, F.: The blood pressure in a population, Acta Med. Scand. (Suppl.):321, 1957. 3. Tibblin, G.: High blood pressure in men aged 50-a population sttidy of men born in 1913, Acta Med. Scand. (Suppl.):470, 1967. 4. Wilhelmsen, L., Berglund, G., and WerkS, L.: Prevalence and management of hypertension in a general population sample of Swedish men, Prey. Med. 2:57, 1973. 5. Sokolow, M, and Perloff, D.: The prognosis of essential hypertension treated conservatively, Circulation 23:697, 1961. 6. Wilhelmsen, L:, Tibblin, G., and Werk6, L.: A primary preventive study in G6teborg, Sweden, Prey. Med. 1:153, 1972. 7. Wilhelmsen, L., Ljungberg, S., Wedel, H., and Werk~, L.:
546
9. 10.
11. 12. 13. 14. 15.
16.
A comparison between participants and iion-participants m a primary preventive trial, J. Chronic Dis. 29:331, 1976. von Euler, U. S., and Floding, I.: Diagnosis of pheochromocytoma by fluorometric estimation of adrenaline and noradrenaline in urine, Scand. J. Clin. Lab. Invest. 8:288, 1956. Berglund, G., Andersson, 0., and Wilhelmsen, L.: Prevalence of primary and secondary hypertension: studies in a random population sample, Bri. Med. J. 2:554, 1976. Dustan, H. P., in The heart and circulation-Second National Conference on Cardiovascular Diseases; Research 1, p. 334. Washington, D.C., 1965, Federation of American Societies for Experimental Biology. Gifford, R. W.: Evaluation of the hypertensive patient with emphasis on detecting curable causes, Milbank Mere. Fund. Qu. 47:170, 1969. Laragh, J. H.: Evaluation and care of the hypertensive patient, Am. J. Med. 52:565, 1972. Fergnson, R. K.: Cost and yield of the hypertensive evaluation, Ann. Intern. Med. 82;761, 1975. Berglund, G.: Pre-treatment workup for antihypertensive treatment, Drugs 1 l:(Suppl 1):60, 1976. McNeil, B. J., Varady, P., Burrows, B. A., and Adelstein, J. A.: Measures of clinical efficacy. Cost-effectiveness calculations in the diagnosis and treatment of hypertensive renovascular disease, N. Engl. J. Med. 293:216, 1975. McNeil, B. J., and Adelstein, S. J.: Measures of clinical efficacy. The vahie of case finding in hypertensive renovascular disease, N. Engl. J. Med. 293:221, 1975.
November, 1977, Vol. 94, No: 5
Heart Journal
November, 1977, Volume 94, N u m b e r 5
Editorial Prevalence of primary and secondary hypertension Lars Wilhelmsen, M.D. G. Berglund, M.D. Goteborg, Sweden
It is well established that the risk of cerebrovascular and cardiovascular complications increases gradually with increasing blood pressure. It is also documented that t h e r e is a high prevalence of blood pressure increase to that level which clearly warrants treatment. 1-4 Thus, 10 to 15 per cent of middle-aged men and women in various countries seem to benefit from treatment. The proportion of the total hypertensive population with demonstrable causes of the hypertension is, however, not definitely known. In various textbooks and reviews the prevalence of secondary hypertension has been estimated to be I0 to 20 per cent. These figures have usually been based on studies in series of hospitalized patients, but there are several reasons t o suspect that the prevalence of secondary hypertension is overestimated in these selected groups of patients. It is important to establish the prevalence of secondary hypertension, since the investigations that are currently undertaken before treatment are largely aimed at detecting secondary forms of hypertension, in which the patients might be cured by specific treatment such as surgery. The diagnostic investigations are also aimed at detecting hypertensive heart complications and renal complications, as these findings have been shown to carry From the Section of Preventive Cardiology, Dept. of Medicine I, Sahlgrenska Hospital, G6teborg, Sweden. Received for publication March 3, 1977. Reprint requests: Lars Wilhelmsen, M.D., Physicfan-in-Chief~ Department of Medicine I, Sahlgrenska Hospital, S:413 45 G6teborg, Sweden.
November, 1977, Vol. 94, No. 5, pp. 543-546
a poorer prognosis, ~ calling for a closer supervision and more intensive treatment. The prevalence of secondary hypertension is certainly not the same in all countries of the world because of varying prevalence of the conditions leading to, for example, renal parenchymal damage, such as glomerulonephritis and pyelonephritis. A decreasing incidence of some of these conditions, such as analgesic nephropathy, is also to be expected. Several investigators have shown that a large part of the hypertensive individuals in different populations are unknown, and any measure aiming at detecting and treating the major part of the hypertensive individuals in a population would increase the cost of the medical services. In this situation it.is important to acquire information concerning the extent of examinations needed. A high prevalence of secondary, presumably curable, hypertension would warrant more extensive preliminary investigations as would a high frequency of patients with hypertensive organ damage. In a recent investigation ~ we have been able to estimate the prevalence of primary and secondary hypertension in middle-aged men in Sweden. Many of the economic and social circumstances as well as the disease panorama of this population is similar to that of several other countries. Thus, it is probable that these findings can be extrapolated to these other populations. The study population consisted of a randomly selected third of all men aged 47 to 54 years and
American Heart Journal
543
Wilhelmsen and Berglund
Table I. The prevalence of primary and secondary hypertension (n -- 686). The number of previously known cases are given with brackets
No. Renoparenchymaldisease Chronic glomerulonephritis Gouty nephropathy Renal tuberculosis Analgesic nephropathy Renal dysplasia Renovascular disease Aortic coarctation Primary ald0steronism Primary hyperparathyroidism Suspected but not proved unilateral hydronephrosis Primary hypertension
25
[ % 3.6
15 (15) 3 (1) 4 (4) 1 (1) 2 (1) 4 (1) 1 (1) 1 (1) 2 (1) 7 (2) 646
0.6 0.1 0.1 0.3 L0 94.2
who were residents of GSteborg, Sweden. These men belonged to the intervention group of a multifactor primary preventive trial2 Of those 9,996 men who were invited to the screening examination 7,455 (75 per cent) attended. It has been shown that the non-participants differed from the participants with respect to mortality and several social variables, but there were no indications that diseases leading to secondary hypertension were more common among the nonparticipants. 7 In the first run, those who were not receiving antihypertensive treatment and whose blood pressures were above 175 mm. Hg systolic blood pressure (SBP) or 115 mm. Hg diastolic blood pressure (DBP) were recalled within 2 weeks to have their blood pressures remeasured. Those who still had blood pressures above these limits and all those who were on antihypertensive treatment were examined for secondary hypertension. The screening methods and the investigations at the Hypertension Clinic have been reported in detail elsewhere?' The examinations of the hypertensive patients consisted of a careful clinical scrutinizing for possible secondary hypertension. The more complicated methods were performed in certain age groups-random samples of the total hypertensive group. The investigations included a complete physical examination with auscultation of the heart and lungs, palpation of the femoral arteries and peripheral pulses, examination of the occular fundi, and a battery of laboratory tests including
544
measurement of serum electrolytes and creatinine, urine test for albuminuria and urinary sediment, urine culture, and determination of renal concentration capacity with a 13-hour thirst test, and, if the latter result was abnormal, a vasopressin tannate test. Isotope renography was carried out in the 287 men born in 1915, 1916, 1920, and 1921 using a standard method and apparatus. Intravenous pyelography (in 52 men) and renal aortography (in 12 men) were also performed with standard methods according to special indications. Catecholamine concentrations were determined in all 58 men born in 1921 using a method described by von Euler and Floding.s On the basis of the results of these investigations and a thorough examination of each patient's c a s e records, a diagnosis was recorded using the criteria given below. Renoparenchymal disease 1. The diagnosis of chronic glomerulonephritis required persistent or intermittent albuminuria or hematuria, or both, without there being another cause of these abnormalities. 2. Renal tuberculosis was recorded when there was a history of pulmonary or renal tuberculosis, or both, with tubercle bacilli in the urine. 3. Gouty nephropathy was recorded in the presence of known arthritis urica and lowered concentration ability (vasopressin t a n n a t e test < 800 mmol./Kg. H20). 4. Renal dysplasia was defined as one small kidney without a history of urinary tract infections. A kidney was considered small if it was over 2 cm. shorter than the other kidney and less than 10 cm. in length with oddly-shaped or club-like calices on the intravenous pyelogram. '1 5. Phenacetin nephropathy was recorded in patients with a long-standing history of abuse, lowered urinary concentration ability, and signs of papillary necrosis on the intravenous pyelogram. 6. Chronic pyelonephritis required a history of recurrent urinary tract infections and a lowered urinary concentration ability. Renovascular disease Screening for renovascular disease was carried out by isotope renography.Patients with abnormal renograms were admitted to hospital for renal aortography and other investigations. Arteriographic verfication was required for a
November, 1977, Vol. 94, No. 5
Primary and secondary hypertension
diagnosis of renal artery stenosis or intrarenal occlusion. Abnormally high ipsilatera! renin secretion or normalization of the blood pressure after surgery was not required for this diagnosis. Isotope renography was als0 performed if there were clinical signs of renovascular disease-for example, abdominal murmurs, drug resistant Or accelerating hypertension, or increasing serum creatinine levels.
Primary aldosteronism A hospital-verified diagnosis was required. Patients with spontaneous hypokalemia or hypokalemia during diuretic treatment whose serum potassium levels did not become normal after Stopping treatment were admitted to hospital for investigation.
Primary hyperparathyroidism A hospital-verified diagnosis was required. Serum calcium and phosphorous were not routinely screened.
Phaochromocytoma A hospital-verified diagnosis was needed. Catecholamines in urine were determined only in men born in 1921. Of~the 7,455 men who were screened, 686 (9 per cent) had hypertension according to the abovementioned criteria. Of these 60 pe r cent were untreated, 23 per cent were treated b u t had blood pressure at screening above S B P 175 or D B P 115 mm. Hg, and only 17 per cent had an acceptable control of their blood pressure. The number and percentage of cases with various types of hypertension appears in Table I. In seven cases of hydronephrosis (two previously known and five newly detected) we could not determine whether or not the hypertension was caused by the hydronephrosis and the resulting partial obstruction to urinary flow. Three patients did not become normotensive after operation and needed continuing antihypertensive treatment, an.d four patients were not operated on because they became normotensive on drug treatment and there were no other indications for operation. Thus, a specific cause of hypertension was found or reasonably suspected in only 40 of the 686 patients (6 per cent). Eight patients had previously undergone surgical treatment, In only two cases did the patients investigation lead to surgical intervention, and both these patients
American Heart Journal
required antihypertensive treatment one year after' their operations, b u t lower doses were needed than before. 9 The methods of recognizing secondary hypertension were those normally used in clinical practice. Owing to the limited capacity of the laboratory, an isotope renogram was carried out only in four randomly selected age groups. In patients with hypertension refractory to treatment, investigation for renovascular causes was also carried out in the other age groups. Thus, most cases of renovascular hypertension amenable to surgical treatment were probably detected. Parenchymatous kidney disease without abnormal laboratory findings and with normal serum creatinine levels and concentration capacity may have been present without being detected. However, these patients had probably minor kidney damage, which in m o s t cases would not have been treated other than with hypotensive drugs even if discovered. Primary aldosteronism was probably excluded with a relatively high degree of certainty. Primary byperparathyroidism as a cause of hypertension may also have been present in more than the two cases who were found in our series since serum calcium was not measured routinely. Thus, the prevalence of secondary hypertension was lower in this study than according to other estimates. ~~ Our analysis is, however, the first one which has been performed in subjects derived from screening of a general population sample. Furthermore, we only studied men aged 47 to 54 years. The prevalence of secondary hypertension might be higher in women or in younger men. Our results suggest, however, that the risk of missing cases of secondary hypertension in middle-aged men is small and extensive investigations do not seem to be necessary in hypertensive subjects found at screening. In patients with hypertension referred to hospital, secondary hypertension is probably over-represented and more extensive routine investigations might be justified. Isotope renography as a screening instrument for renovascular hypertension cannot be recommended. The prevalence of renovascular hypertension was low, and there were many false positive renograms. TM Thus, our results support the bad cost-benefit ratio found in recent analyses of urography and isotope renography as screening instruments for renovascular hyperten-
545
Wilhelmsen and Berglund
sion, 15and of comparisons of surgical and medical treatment of renovascular hypertension. 16 Thus, the present data indicate t h a t the resources for
8.
management Of hypertension should be devoted more to case-finding and treatment t h a n to elabo, rate investigative measures.
REFERENCES
1. National Health Survey: H~pertension and hypertensive heart disease in adults, Washington, i966, Public Health Service PUblications. 2. BSb J., Humerfelt, S, and Wed,rvang, F.: The blood pressure in a population, Acta Med. Scand. (Suppl.):321, 1957. 3. Tibblin, G.: High blood pressure in men aged 50-a population sttidy of men born in 1913, Acta Med. Scand. (Suppl.):470, 1967. 4. Wilhelmsen, L., Berglund, G., and WerkS, L.: Prevalence and management of hypertension in a general population sample of Swedish men, Prey. Med. 2:57, 1973. 5. Sokolow, M, and Perloff, D.: The prognosis of essential hypertension treated conservatively, Circulation 23:697, 1961. 6. Wilhelmsen, L:, Tibblin, G., and Werk6, L.: A primary preventive study in G6teborg, Sweden, Prey. Med. 1:153, 1972. 7. Wilhelmsen, L., Ljungberg, S., Wedel, H., and Werk~, L.:
546
9. 10.
11. 12. 13. 14. 15.
16.
A comparison between participants and iion-participants m a primary preventive trial, J. Chronic Dis. 29:331, 1976. von Euler, U. S., and Floding, I.: Diagnosis of pheochromocytoma by fluorometric estimation of adrenaline and noradrenaline in urine, Scand. J. Clin. Lab. Invest. 8:288, 1956. Berglund, G., Andersson, 0., and Wilhelmsen, L.: Prevalence of primary and secondary hypertension: studies in a random population sample, Bri. Med. J. 2:554, 1976. Dustan, H. P., in The heart and circulation-Second National Conference on Cardiovascular Diseases; Research 1, p. 334. Washington, D.C., 1965, Federation of American Societies for Experimental Biology. Gifford, R. W.: Evaluation of the hypertensive patient with emphasis on detecting curable causes, Milbank Mere. Fund. Qu. 47:170, 1969. Laragh, J. H.: Evaluation and care of the hypertensive patient, Am. J. Med. 52:565, 1972. Fergnson, R. K.: Cost and yield of the hypertensive evaluation, Ann. Intern. Med. 82;761, 1975. Berglund, G.: Pre-treatment workup for antihypertensive treatment, Drugs 1 l:(Suppl 1):60, 1976. McNeil, B. J., Varady, P., Burrows, B. A., and Adelstein, J. A.: Measures of clinical efficacy. Cost-effectiveness calculations in the diagnosis and treatment of hypertensive renovascular disease, N. Engl. J. Med. 293:216, 1975. McNeil, B. J., and Adelstein, S. J.: Measures of clinical efficacy. The vahie of case finding in hypertensive renovascular disease, N. Engl. J. Med. 293:221, 1975.
November, 1977, Vol. 94, No: 5
