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Association of hypertension and mitral stenosis
&J&)@IATION
OF HYPERTENSION
.&-$I) .h~Ir~B-k!,
8’~!?~?dth’S
HOWARD L. HORNS, M.D.* BIINNEAPOLIS, BETAIN
special
&IITs.
r&tion&ips
ha-ye
heel1
su~~esi~d
xgarding
;:.lti
development of hypertension in persons whtkve mitral stenok The first of these is that elevated blood pressure tends to ameliorate the Levine,l in considering this clinical course of the valvular disability. “ A!t,hough. it may add association, summarizes his views as follows: e&ail1 symptoms as a result of the hypertension itself, when these are not severe, there is reason to believe that it delays the progress ibf mitral stenosis. It is curious that so many patients ivith mitral stenosis I believe lhar over fifty years of age have hypertension in addition. hypertension prolongs their lives and enables them to reach the latter decades. ” Levine suggests two factors as being possibly responsible for ?;he beneficial effect which he notes. One is that the hypertension tends to induce and maintain enlargement and dilatat,ion of the left ventricle, and that this dilatation opposesand delays the contraction of the mitral ring. The second factor which he considers is that the su.perimpo&ion of hypertension upon mitral stenosis equalizes t&e burdens upon the i.wo s,idesof the heart, and thus delays t,he development, of an imbalance between them. In addition to this salutory influence, it has been suggested that persons with mitral stenosis develop hypertension with greater frequency than do those of the general population. Levine feels that such an increased incidence occurs in the age range beyond 45 years, but that there is a tendency toward decreased blood pressure in the younger group o.C persons with mitral disease. He considers that a possible explanation is that the chronic rheumatic infection responsible for the valvular lesion may also insidiously produce widespread vascular damsge which lat,er result,s in hypertension. However, he thinks it more likely that cert.ain persons have what he calls “vascular vulnerability,’ ’ which reuders them more susceptible to both rheumatic fever and the later develol)ment of hypertension. Although the first of these two relationships is o?l greater elinicai interest and largely conditions the interest in the latter, it will receive ouly subsidiary consideration here because of the limitations of the material available. The primary problem with which the present study is concerned is the relative frequency of the development of hypertension in persons with mitral $enosis. .Received ‘From
for the
publication Departments
Oct. 3, 1943. of Medicine
Pathology, University 435
and
of Minnesota.
436
AMERICAN
HEART
JOURXAL
The literature regarding the question is not voluminous. Boas and Fineberg, in reviewini it in 1926, found that Bamberger, in 1857, had noted a frequent association of valvular heart disease and granular kidneys. Goodhart, in 1880, described the frequent occurence of granular kidneys in patients with mitral thickening and stenosis. Pitt, in 1888, surveying a large necropsy material, reported that one-third of females and one-fifth of males with mitral stenosis also had granular kidneys. Both Gibson and Coombs had noted the common occurrence of high arterial pressure in patients with mitral stenosis. In conjunction with this review of the literature, Boas and Fineberg’ reported a study of the blood pressure in 135 cases of mitral stenosis. Using a blood pressure in excess of 150, systolic, and 90, diastolic, as a criterion of hypertension, they found an incidence of 29 per cent (thirtynine cases) in their tot,al group whose age range was from 1 year to over 60 years of age. Sixty-seven of these were over 40 years of age, and, in this age range, the incidence of hypertension was 55 per cent. They compared these frequencies with the 11 per cent incidence in a group of 3,778 hospital patients who were unselected for age and sex. Levine and Fulton3 studied a series of 762 cases of mitral stenosis in which the ages ranged from 5 to over 70 years. One hundred fifty-nine of these patients were over 45 years, and, of them, ninety-two, or 58 per cent, had hypertension by the same criterion as that employed by Boas and Fineberg. Their conclusion was that “with advancing years patients with mitral stenosis have vascular hypertension with much greater frequency than the average population. ” Brumm and Smith,4 however, in reviewing 1,925 patients of all ages at the Mayo Clinic, found that only fort,y-four, or 2.3 per cent, had hypertension associated with mitral stenosis. Although their criterion of hypertension was not mentioned, it seems reasonable to assume from the fact that the lowest blood pressure in their hypertensive group was 152, systolic, and 90, diastolic, that it was approximately the same as that employed in the other two studies. They further concluded that the hypertension in these patients exerted no beneficial effect. The material for the present study consists of cases of proved mitral stenosis, taken from the autopsy records of the pathology department of the University of Minnesota Medical School. Because of the possible mechanical effects of aortic valvular lesions upon blood pressure, all cases in which there was accompanyin, 0 aortic valve involvement were excluded. However, in some instances there was an associated mitral regurgitation. All were cases of persons who died in Twin City hospitals during the period between 1929 and 1940. The blood pressures were taken from the hospital charts, either directly or as recorded on the autopsy reports; in those instances in which more than one blood pressure reading was recorded, the highest valui: was taken. Cases in which the patient was in coma or in which the blood pressure was taken within
death were excluded. The final group consisted of i& cases with an age range of 20 to 87 years ; forty-three (30 per cerrtj were males, and 101 (70 per cent) were females. As a control group, a stratified sample of 288 cases, exactly mazching the mitral group with respect to age and sex, wa.s taken at random irom the records of the out-patient clinic of the University Hospital, The blood pressures of these patients were those recorded at their initial physical examinations in the clinic. Following the precedent of the studies noted above, a blood pressure XI excess of 150, systolic, and 90, diastolic, was taken as the arbitrary criterion of hypertension. Because of the emphasis upon the factor of age by Levine and F&on, their procedure of dividing the total grotxrl_’ into two subgroups, with the age of 45 years as the point of division, was also employed here. These conditions afford two bases of comparison ldween the mit,ral and control groups and between their respective subgroupings. They are first compared with regard to the frequency of the arbitrarily defined hypertension, and, second, on the basis of the average values for systolic and diastolic pressures. The results of the first comparison for the total groups, for the subgroup over the age of 45, and for the subgroup under the age of 45 years are summarized in Table I. The differenees observed are, in all cases, slight; the greatest critical ratio was 1.35, and therefore they fail to satisfy a,ny of the criteria of statistical significance. In particular, the irequencies in which we are the most interested, namely, those for ‘;hc age range over 45 years: are nearly identical for the mitral and control groups. As noted, the values are 30 and 31 per cent: respectively,
twelve
hours
of
TABLE
1
TOTAL MITRAL
___-___
Number of Cases Number with Hypertension Percentage with Hypertension Stanllard deviation
~-.----_
__
_______ 144 34 23.6 3.6 I Difference S. D. / Critical difference ,
ratio
OVER AGE 45
CONTROL
MITRAL
____91 37
288 62 31.6
’
35
182 56 i
4.9 2 Diderence 5. D. 4.33 dif-l-erenee Critical .46 ratio
2.4
._ MITRAL .____--______
CONTROL
1 CONTROL
53
106 6
7
31
13
3.4
- 4.6 1 Difference
5.96
s. n.
difference
/
6
/
2.3 7 5.1::
Critical
.17 L
ratio
1.35
This observed difference of 1 per cent is actually in the reverse direetion from that expected and has a standard deviafion of 5.96, which means thai the chances that such a difference would occur by the aeeident of random sampling are about eighty-five in a hundred.
438
AMERICAN
HEART
TABLE AVERAGE
SYSTOLIC
Control Mitral Difference 8. D. difference Critical, ratio
BLOOD
PRESSURES
DIASTOLIC
AND
MITRAL
GROUPS
OVER AGE 45 148.2 ? 2.34 144.4 t 3.02
.96 2.78 .34
3.8 3.81
4.1
1
1.2
PRESSURES TOTAL
Control Mitral Difference 8. D. difference Critical, ratio
II FOR CONTROL
TOTAL 139.86 +_ 1.68 138.9 2 2.23
TABLE AVERAGE
JOURNAL
85.7 54.4
GROUP t .91 t 1.35 1.3 1.68 .75
UNDER
AGE 45 2 1.79 + 2.88
125.5
129.6
3.39
III
FOR CONTROL
AND
OVER AGE 45 88.9 t 1.09 86.2 t 1.75 2.7 2.05 1.32
MITRAL
GROUPS UNDER 80.3 81.5
AGE 45 2 2.3 +_ 2.03 1.2 2.3 .52
A comparison of the mitral groups with their corresponding controls on a basis of average systolic and diastolic pressures (Tables II and III) likewise results in small differences which are not statistically significant. The highest critical ratio among these is 1.32. Here, too, the observed, slight difference for the subgroup over the age of 45 years is actually the opposite of that suggested. For the mitral group, the average blood pressure was 144.4 + 3.02, systolic, and 86.2 + 1.75, diastolic, as compared to the control values of 148.2 + 2.34 and 88.9 + 1.09. An additional check upon the control group, averages of systolic and diastolic pressures, weighted for age and sex to correspond with the control group employed, were calculated from the values given by Wetherby.5 These values were ascertained from a study of 5,540 persons of the same population from which the control group for the present study was selected. The averages thus calculated are 143, systolic, and 86, diastolic, and compare closely with the 139.86, systolic, and 85.7, diastolic, found in the present study. It does not appear therefore, that any considerable selective factor was operative in determining the present control group. Finally, the mitral group of 144 cases was divided into those with hypertension and those without, and the average age at death of these two groups was compared. The average age at death for those with hypertension was 56.5 + 2.19, and for those without, 48.9 & 2.58. The difference of 7.6 + 2.55 may be considered as bordering on statistical significance. However, it is not safe to conclude from this that the presence of hypertension confers an increased life expectancy upon a person with mitral disease. Hypertension and age are not independent variables; the former occurs with increasing frequency at higher ages, and, for that reason, the selection of a group on a basis of hypertension entails the artificial selection of those in the higher age range. ,The objection may be raised that the blood pressures recorded for the autopsy group of cases of mitral stenosis are spuriously low because
E-IORNS
:
HYPERTEKSION
AND
MITRAL
STENOSlS
i&>
they were taken after the onset of heart failure in most cases; and JIM hospitalized patients, whereas those for the control group were taken An attempt was made to avoid the largely on ambulatory patients. terminal fall in blood pressure by excluding those cases in which ihe recording was made within twelve hours of death. Furthermore, a la11 in blood pressure with the onset of heart failure with mitral stenosis In considering this question, Fishberg” does not appear to be the rule. SCiYS, “Sometimes the systolic and pulse pressure fall slightly. More often the onset of heart failure in mitral stenosis is accompanied by a rise in the diastolic pressure with a smaller increase in s>-stolic pressure. ” He also reports, “Lang and Manswetowa found that as a. rule a break in compensation in cardiac disease is accompanied by a rise in arterial pressure which falls again as the heart improves. This was especially often the case in mitral disease and emphysema heart. ‘: Finally, it seems unlikely that false readings due to the patients’ CODdition would, in a group of this size, so exactly counterbalance an acti.iat difference as to yield the observed close agreement CONCLUSIOKS
It is somewhat hazardous to draw sweeping conclusions from small samples, however rigorous statistical precautions may be exercised. appears, however, that the close agreement,s which were found iu the present study between mitral and control groups by all methods of eomparison justify at least a skeptical attitude toward the assertion that there is a higher frequency of hypert,ension among persons with mitral stenosis than obtains in the general population. From the evidence presented, nothing can be concluded concerning the efrect of hypertension upon the clinica,] course of mitral stenosis. REFZRENCES 1. lievine, 8. A.: Clinical Heart Disease, Philatlelphia, 1949, W. 33. Saunders Cornwy. 9. Boas, E. P., and Fineberg, M. H.: Hypertension in Its Relationship to Mitral Stenosis and Aortic InsufEciency, Am. J. 35. SC. 172: 648, 1926. :3. Levine, 8. A., and Fulton, M. N.: The Relation of Hypert.ension to Mitral Stenosis, Am. J. M. SC. 176: 465, 1928. 4. Brumm, H. J., and Smith, H. L.: Hypertension Associated With Mitral Sten:&; Report of 44 Cases, Minnesota, Med. 24: 664, 1941. 5. Wetherby, M.: A Comparison of Blood Pressure in Men and Women; Statistica: Study of 5,540 Individuals, Ann. Int. Ned. 6: 754, 1932. 6. Fishberg, A. M.: Heart Failure, Philadelphia, 1940, Lea & Febiger.
OF HYPERTENSION
.&-$I) .h~Ir~B-k!,
8’~!?~?dth’S
HOWARD L. HORNS, M.D.* BIINNEAPOLIS, BETAIN
special
&IITs.
r&tion&ips
ha-ye
heel1
su~~esi~d
xgarding
;:.lti
development of hypertension in persons whtkve mitral stenok The first of these is that elevated blood pressure tends to ameliorate the Levine,l in considering this clinical course of the valvular disability. “ A!t,hough. it may add association, summarizes his views as follows: e&ail1 symptoms as a result of the hypertension itself, when these are not severe, there is reason to believe that it delays the progress ibf mitral stenosis. It is curious that so many patients ivith mitral stenosis I believe lhar over fifty years of age have hypertension in addition. hypertension prolongs their lives and enables them to reach the latter decades. ” Levine suggests two factors as being possibly responsible for ?;he beneficial effect which he notes. One is that the hypertension tends to induce and maintain enlargement and dilatat,ion of the left ventricle, and that this dilatation opposesand delays the contraction of the mitral ring. The second factor which he considers is that the su.perimpo&ion of hypertension upon mitral stenosis equalizes t&e burdens upon the i.wo s,idesof the heart, and thus delays t,he development, of an imbalance between them. In addition to this salutory influence, it has been suggested that persons with mitral stenosis develop hypertension with greater frequency than do those of the general population. Levine feels that such an increased incidence occurs in the age range beyond 45 years, but that there is a tendency toward decreased blood pressure in the younger group o.C persons with mitral disease. He considers that a possible explanation is that the chronic rheumatic infection responsible for the valvular lesion may also insidiously produce widespread vascular damsge which lat,er result,s in hypertension. However, he thinks it more likely that cert.ain persons have what he calls “vascular vulnerability,’ ’ which reuders them more susceptible to both rheumatic fever and the later develol)ment of hypertension. Although the first of these two relationships is o?l greater elinicai interest and largely conditions the interest in the latter, it will receive ouly subsidiary consideration here because of the limitations of the material available. The primary problem with which the present study is concerned is the relative frequency of the development of hypertension in persons with mitral $enosis. .Received ‘From
for the
publication Departments
Oct. 3, 1943. of Medicine
Pathology, University 435
and
of Minnesota.
436
AMERICAN
HEART
JOURXAL
The literature regarding the question is not voluminous. Boas and Fineberg, in reviewini it in 1926, found that Bamberger, in 1857, had noted a frequent association of valvular heart disease and granular kidneys. Goodhart, in 1880, described the frequent occurence of granular kidneys in patients with mitral thickening and stenosis. Pitt, in 1888, surveying a large necropsy material, reported that one-third of females and one-fifth of males with mitral stenosis also had granular kidneys. Both Gibson and Coombs had noted the common occurrence of high arterial pressure in patients with mitral stenosis. In conjunction with this review of the literature, Boas and Fineberg’ reported a study of the blood pressure in 135 cases of mitral stenosis. Using a blood pressure in excess of 150, systolic, and 90, diastolic, as a criterion of hypertension, they found an incidence of 29 per cent (thirtynine cases) in their tot,al group whose age range was from 1 year to over 60 years of age. Sixty-seven of these were over 40 years of age, and, in this age range, the incidence of hypertension was 55 per cent. They compared these frequencies with the 11 per cent incidence in a group of 3,778 hospital patients who were unselected for age and sex. Levine and Fulton3 studied a series of 762 cases of mitral stenosis in which the ages ranged from 5 to over 70 years. One hundred fifty-nine of these patients were over 45 years, and, of them, ninety-two, or 58 per cent, had hypertension by the same criterion as that employed by Boas and Fineberg. Their conclusion was that “with advancing years patients with mitral stenosis have vascular hypertension with much greater frequency than the average population. ” Brumm and Smith,4 however, in reviewing 1,925 patients of all ages at the Mayo Clinic, found that only fort,y-four, or 2.3 per cent, had hypertension associated with mitral stenosis. Although their criterion of hypertension was not mentioned, it seems reasonable to assume from the fact that the lowest blood pressure in their hypertensive group was 152, systolic, and 90, diastolic, that it was approximately the same as that employed in the other two studies. They further concluded that the hypertension in these patients exerted no beneficial effect. The material for the present study consists of cases of proved mitral stenosis, taken from the autopsy records of the pathology department of the University of Minnesota Medical School. Because of the possible mechanical effects of aortic valvular lesions upon blood pressure, all cases in which there was accompanyin, 0 aortic valve involvement were excluded. However, in some instances there was an associated mitral regurgitation. All were cases of persons who died in Twin City hospitals during the period between 1929 and 1940. The blood pressures were taken from the hospital charts, either directly or as recorded on the autopsy reports; in those instances in which more than one blood pressure reading was recorded, the highest valui: was taken. Cases in which the patient was in coma or in which the blood pressure was taken within
death were excluded. The final group consisted of i& cases with an age range of 20 to 87 years ; forty-three (30 per cerrtj were males, and 101 (70 per cent) were females. As a control group, a stratified sample of 288 cases, exactly mazching the mitral group with respect to age and sex, wa.s taken at random irom the records of the out-patient clinic of the University Hospital, The blood pressures of these patients were those recorded at their initial physical examinations in the clinic. Following the precedent of the studies noted above, a blood pressure XI excess of 150, systolic, and 90, diastolic, was taken as the arbitrary criterion of hypertension. Because of the emphasis upon the factor of age by Levine and F&on, their procedure of dividing the total grotxrl_’ into two subgroups, with the age of 45 years as the point of division, was also employed here. These conditions afford two bases of comparison ldween the mit,ral and control groups and between their respective subgroupings. They are first compared with regard to the frequency of the arbitrarily defined hypertension, and, second, on the basis of the average values for systolic and diastolic pressures. The results of the first comparison for the total groups, for the subgroup over the age of 45, and for the subgroup under the age of 45 years are summarized in Table I. The differenees observed are, in all cases, slight; the greatest critical ratio was 1.35, and therefore they fail to satisfy a,ny of the criteria of statistical significance. In particular, the irequencies in which we are the most interested, namely, those for ‘;hc age range over 45 years: are nearly identical for the mitral and control groups. As noted, the values are 30 and 31 per cent: respectively,
twelve
hours
of
TABLE
1
TOTAL MITRAL
___-___
Number of Cases Number with Hypertension Percentage with Hypertension Stanllard deviation
~-.----_
__
_______ 144 34 23.6 3.6 I Difference S. D. / Critical difference ,
ratio
OVER AGE 45
CONTROL
MITRAL
____91 37
288 62 31.6
’
35
182 56 i
4.9 2 Diderence 5. D. 4.33 dif-l-erenee Critical .46 ratio
2.4
._ MITRAL .____--______
CONTROL
1 CONTROL
53
106 6
7
31
13
3.4
- 4.6 1 Difference
5.96
s. n.
difference
/
6
/
2.3 7 5.1::
Critical
.17 L
ratio
1.35
This observed difference of 1 per cent is actually in the reverse direetion from that expected and has a standard deviafion of 5.96, which means thai the chances that such a difference would occur by the aeeident of random sampling are about eighty-five in a hundred.
438
AMERICAN
HEART
TABLE AVERAGE
SYSTOLIC
Control Mitral Difference 8. D. difference Critical, ratio
BLOOD
PRESSURES
DIASTOLIC
AND
MITRAL
GROUPS
OVER AGE 45 148.2 ? 2.34 144.4 t 3.02
.96 2.78 .34
3.8 3.81
4.1
1
1.2
PRESSURES TOTAL
Control Mitral Difference 8. D. difference Critical, ratio
II FOR CONTROL
TOTAL 139.86 +_ 1.68 138.9 2 2.23
TABLE AVERAGE
JOURNAL
85.7 54.4
GROUP t .91 t 1.35 1.3 1.68 .75
UNDER
AGE 45 2 1.79 + 2.88
125.5
129.6
3.39
III
FOR CONTROL
AND
OVER AGE 45 88.9 t 1.09 86.2 t 1.75 2.7 2.05 1.32
MITRAL
GROUPS UNDER 80.3 81.5
AGE 45 2 2.3 +_ 2.03 1.2 2.3 .52
A comparison of the mitral groups with their corresponding controls on a basis of average systolic and diastolic pressures (Tables II and III) likewise results in small differences which are not statistically significant. The highest critical ratio among these is 1.32. Here, too, the observed, slight difference for the subgroup over the age of 45 years is actually the opposite of that suggested. For the mitral group, the average blood pressure was 144.4 + 3.02, systolic, and 86.2 + 1.75, diastolic, as compared to the control values of 148.2 + 2.34 and 88.9 + 1.09. An additional check upon the control group, averages of systolic and diastolic pressures, weighted for age and sex to correspond with the control group employed, were calculated from the values given by Wetherby.5 These values were ascertained from a study of 5,540 persons of the same population from which the control group for the present study was selected. The averages thus calculated are 143, systolic, and 86, diastolic, and compare closely with the 139.86, systolic, and 85.7, diastolic, found in the present study. It does not appear therefore, that any considerable selective factor was operative in determining the present control group. Finally, the mitral group of 144 cases was divided into those with hypertension and those without, and the average age at death of these two groups was compared. The average age at death for those with hypertension was 56.5 + 2.19, and for those without, 48.9 & 2.58. The difference of 7.6 + 2.55 may be considered as bordering on statistical significance. However, it is not safe to conclude from this that the presence of hypertension confers an increased life expectancy upon a person with mitral disease. Hypertension and age are not independent variables; the former occurs with increasing frequency at higher ages, and, for that reason, the selection of a group on a basis of hypertension entails the artificial selection of those in the higher age range. ,The objection may be raised that the blood pressures recorded for the autopsy group of cases of mitral stenosis are spuriously low because
E-IORNS
:
HYPERTEKSION
AND
MITRAL
STENOSlS
i&>
they were taken after the onset of heart failure in most cases; and JIM hospitalized patients, whereas those for the control group were taken An attempt was made to avoid the largely on ambulatory patients. terminal fall in blood pressure by excluding those cases in which ihe recording was made within twelve hours of death. Furthermore, a la11 in blood pressure with the onset of heart failure with mitral stenosis In considering this question, Fishberg” does not appear to be the rule. SCiYS, “Sometimes the systolic and pulse pressure fall slightly. More often the onset of heart failure in mitral stenosis is accompanied by a rise in the diastolic pressure with a smaller increase in s>-stolic pressure. ” He also reports, “Lang and Manswetowa found that as a. rule a break in compensation in cardiac disease is accompanied by a rise in arterial pressure which falls again as the heart improves. This was especially often the case in mitral disease and emphysema heart. ‘: Finally, it seems unlikely that false readings due to the patients’ CODdition would, in a group of this size, so exactly counterbalance an acti.iat difference as to yield the observed close agreement CONCLUSIOKS
It is somewhat hazardous to draw sweeping conclusions from small samples, however rigorous statistical precautions may be exercised. appears, however, that the close agreement,s which were found iu the present study between mitral and control groups by all methods of eomparison justify at least a skeptical attitude toward the assertion that there is a higher frequency of hypert,ension among persons with mitral stenosis than obtains in the general population. From the evidence presented, nothing can be concluded concerning the efrect of hypertension upon the clinica,] course of mitral stenosis. REFZRENCES 1. lievine, 8. A.: Clinical Heart Disease, Philatlelphia, 1949, W. 33. Saunders Cornwy. 9. Boas, E. P., and Fineberg, M. H.: Hypertension in Its Relationship to Mitral Stenosis and Aortic InsufEciency, Am. J. 35. SC. 172: 648, 1926. :3. Levine, 8. A., and Fulton, M. N.: The Relation of Hypert.ension to Mitral Stenosis, Am. J. M. SC. 176: 465, 1928. 4. Brumm, H. J., and Smith, H. L.: Hypertension Associated With Mitral Sten:&; Report of 44 Cases, Minnesota, Med. 24: 664, 1941. 5. Wetherby, M.: A Comparison of Blood Pressure in Men and Women; Statistica: Study of 5,540 Individuals, Ann. Int. Ned. 6: 754, 1932. 6. Fishberg, A. M.: Heart Failure, Philadelphia, 1940, Lea & Febiger.