Acta med. scand. Vol. 199, pp. 75-79, 1976
Enzymes and Long-term Survival after First Myocardial Infarction K. Thygesen, B. Lyager Nielsen and J . Strade Nielsen From Department of Medicine B , Odense University Hospital. Odense, Denmcirk
ABSTRACT. The study covers 342 patients still alive one month afier the acute attack of their first rnyocardial infarction. Daily determinations of creatinine phosphokinase (CPK), lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) in serum were carried out during hospitalization, so that a maximum enzyme value could be obtained for each enzyme and patient. A follow-up examination was performed after an observation time ranging from 12 to 38 months. Having calculated the mean (x) of the maximum enzyme values, a parallel relationship was found between the maximum CPK, LDH and SGOT values and the long-term prognosis in myocardial infarction, inasmuch as patients with maximum enzyme values above or equal to the mean had a significantly higher 2-year mortality than patients with values below f. In order to detect any slight difference between the three enzymes with reference to the long-term prognosis, the material was divided into four groups: one with peak values less than 2 4 2 (lowest), one with values from 2 4 2 to 2 exclusive (next lowest), one with values from 1 to 2+2/2 exclusive (next highest) and a group with peak elevations greater than or equal to 2+2/2 (highest). A tendency to inc'reasing mortality from the next lowest to the highest maximum enzyme values was found. On the other hand, patients with the lowest peak values had a tendency to higher mortality than patients in the next lowest group. This characteristic was observed with regard to both CPK and LDH and to some extent to SGOT.
The size of the infarction and the functional capacity of the remaining myocardium are important factors for the prognosis when evaluating the longterm survival following acute myocardial infarction (AMI). As a number of investigations (7, 8, 13, 15, 21) have shown that there is a positive correlation be-
tween maximum enzyme values of lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) in serum and the size of a myocardial infarction, one would expect the maximum enzyme values to yield information as to the long-term prognosis in AMI. The few studies which have been carried out to date (6, 10, 12, 13) have on the whole confirmed this assumption, but the results are somewhat ambiguous, besides being difficult to compare owing to the use of different enzyme units and in some cases comprising only a small number of patients. The relationship between serum creatinine phosphokinase (CPK) and long-term survival in AM1 has apparently not been studied before. The object of the present study has been, on the basis of a reasonably large material, to evaluate both the relationship between maximum values of CPK, LDH and SGOT and long-term survival following AM1 and also the importance of the three enzymes as indicators of the long-term prognosis. MATERIAL AND METHODS The study covers 263 men and 79 women who had been admitted to the Coronary Care Unit (CCU) of the University Hospital of Odense from Nov. 1969 to Dec. 1971. All had AM1 according to the following definitions: precordial pain of long duration and/or acute pulmonary edema in connection with the occurrence of signs of infarction on ECG and/or characteristic increase in enzymes. In addition the following criteria were fulfilled by all patients: 1) first myocardial infarction, 2) admission to the CCU within 24 hours of the onset of symptoms, 3) survival after the acute phase (days &30 inclusive). Enzyme analysis
Blood samples for enzyme analysis were drawn from the majority of patients immediately after admission. The analysis was carried out, depending upon the time of admission, either immediately after sampling or at the Aria med. scand. 199
76
K . Thygesen et a[.
Table I. The day follolting ridmission on which enzyme values reached u mri.rimutn Enzyme (U/U CPK LDH SGOT
Par ccnf mrvivors
Day 1
2
3
4
5
26
58 13 39
220 69 194
53 192 87
7 53 9
2 10 7
2 5 6
40
I20‘
ts,
0
next routine analysis (on serum stored at 4°C). In the following days the blood samples were taken between 7.30 and 10.00 and the analysis was carried out immediately. In the study period the CPK analyses were carried out manually according to a modification of the method of Tanzer and Gilvarg (20). The variation coefficient ( 1 daily control for 10 months) was 9. I %. The normal range for men was 1.0-8.2 U/I and for women 0.9-4.4 U/l. The LDH determinations were carried out using the “Autochemist” according to a colorimetric method (2). The variation coefficient (6 controls daily for 5 months) was 3.7% and the normal range 98-216 U/I. SGOT values were determined by autoanalytic technic (“Autochemist”) according to a colorimetric method (9, 18). The variation coefficient (6 controls daily for 5 months) was 3%. The normal range was 2-15 U/I. Daily estimations of CPK, LDH and SGOT values were carried out in the majority of patients until normal values were obtained. Thus a peak value for each of the three enzymes could be obtained for every patient. Table I shows the day with maximum enzyme values. Maximum enzyme values were used in the following calculations. No significant difference was found between the maximum enzyme values in men and women or between younger and older patients (17). Thus no allowance has been made in the calculations for age or sex. FOIIOW-UP The patients were followed up on Jan. 1st 1973. The minimum period of observation was 12 months, the maximum 38 months. Information regarding the patients was Ar cent
survivors
1 )____. CPK.
40
i* Y
CPU ? 1 . 5 4
,m ‘l4
0
(M .? (0
f
,
bl
I
2
3
I, C P X . 9 I . CPK z i
Olservafion fimc ,n years
Fig. 1 . Survival curves of patients alive one month after first myocardial infarction, according to maximum values of CPK. Acta med. scand. 199
LDH ‘ i . 8 0 0
*---- lo“
= i. a 0 0 1,’ 1’1
f
#I
++ 2
Observation fime
, I
,. I.
‘08.I
U“.i
3 in ywm
F;g. 2 . Survival curves of patients alive one month after first myocardial infarction, according to maximum values of LDH.
obtained from hospital records, National Registration Offices, general practitioners, Medical Officers of Health and the Central Register of Deaths of the National Health Service. Of the 342 patients, 339 were traced. The remaining 3 were foreigners, who had been visiting this country; all three were discharged alive. Statistical analysis The actuarial method has been employed in the calculation of survival probability (3). Confidence limits of 95% have been used in the survival curves. The standard deviation has been calculated with the ”Greenwood’s estimate”. Statistical comparison between the survival rates has been carried out partly by evaluation of the curves with safety intervals and partly using the 2xnx2 test, where n is the number of observatior? intervals (1). For p
Enzymes and Long-term Survival after First Myocardial Infarction K. Thygesen, B. Lyager Nielsen and J . Strade Nielsen From Department of Medicine B , Odense University Hospital. Odense, Denmcirk
ABSTRACT. The study covers 342 patients still alive one month afier the acute attack of their first rnyocardial infarction. Daily determinations of creatinine phosphokinase (CPK), lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) in serum were carried out during hospitalization, so that a maximum enzyme value could be obtained for each enzyme and patient. A follow-up examination was performed after an observation time ranging from 12 to 38 months. Having calculated the mean (x) of the maximum enzyme values, a parallel relationship was found between the maximum CPK, LDH and SGOT values and the long-term prognosis in myocardial infarction, inasmuch as patients with maximum enzyme values above or equal to the mean had a significantly higher 2-year mortality than patients with values below f. In order to detect any slight difference between the three enzymes with reference to the long-term prognosis, the material was divided into four groups: one with peak values less than 2 4 2 (lowest), one with values from 2 4 2 to 2 exclusive (next lowest), one with values from 1 to 2+2/2 exclusive (next highest) and a group with peak elevations greater than or equal to 2+2/2 (highest). A tendency to inc'reasing mortality from the next lowest to the highest maximum enzyme values was found. On the other hand, patients with the lowest peak values had a tendency to higher mortality than patients in the next lowest group. This characteristic was observed with regard to both CPK and LDH and to some extent to SGOT.
The size of the infarction and the functional capacity of the remaining myocardium are important factors for the prognosis when evaluating the longterm survival following acute myocardial infarction (AMI). As a number of investigations (7, 8, 13, 15, 21) have shown that there is a positive correlation be-
tween maximum enzyme values of lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) in serum and the size of a myocardial infarction, one would expect the maximum enzyme values to yield information as to the long-term prognosis in AMI. The few studies which have been carried out to date (6, 10, 12, 13) have on the whole confirmed this assumption, but the results are somewhat ambiguous, besides being difficult to compare owing to the use of different enzyme units and in some cases comprising only a small number of patients. The relationship between serum creatinine phosphokinase (CPK) and long-term survival in AM1 has apparently not been studied before. The object of the present study has been, on the basis of a reasonably large material, to evaluate both the relationship between maximum values of CPK, LDH and SGOT and long-term survival following AM1 and also the importance of the three enzymes as indicators of the long-term prognosis. MATERIAL AND METHODS The study covers 263 men and 79 women who had been admitted to the Coronary Care Unit (CCU) of the University Hospital of Odense from Nov. 1969 to Dec. 1971. All had AM1 according to the following definitions: precordial pain of long duration and/or acute pulmonary edema in connection with the occurrence of signs of infarction on ECG and/or characteristic increase in enzymes. In addition the following criteria were fulfilled by all patients: 1) first myocardial infarction, 2) admission to the CCU within 24 hours of the onset of symptoms, 3) survival after the acute phase (days &30 inclusive). Enzyme analysis
Blood samples for enzyme analysis were drawn from the majority of patients immediately after admission. The analysis was carried out, depending upon the time of admission, either immediately after sampling or at the Aria med. scand. 199
76
K . Thygesen et a[.
Table I. The day follolting ridmission on which enzyme values reached u mri.rimutn Enzyme (U/U CPK LDH SGOT
Par ccnf mrvivors
Day 1
2
3
4
5
26
58 13 39
220 69 194
53 192 87
7 53 9
2 10 7
2 5 6
40
I20‘
ts,
0
next routine analysis (on serum stored at 4°C). In the following days the blood samples were taken between 7.30 and 10.00 and the analysis was carried out immediately. In the study period the CPK analyses were carried out manually according to a modification of the method of Tanzer and Gilvarg (20). The variation coefficient ( 1 daily control for 10 months) was 9. I %. The normal range for men was 1.0-8.2 U/I and for women 0.9-4.4 U/l. The LDH determinations were carried out using the “Autochemist” according to a colorimetric method (2). The variation coefficient (6 controls daily for 5 months) was 3.7% and the normal range 98-216 U/I. SGOT values were determined by autoanalytic technic (“Autochemist”) according to a colorimetric method (9, 18). The variation coefficient (6 controls daily for 5 months) was 3%. The normal range was 2-15 U/I. Daily estimations of CPK, LDH and SGOT values were carried out in the majority of patients until normal values were obtained. Thus a peak value for each of the three enzymes could be obtained for every patient. Table I shows the day with maximum enzyme values. Maximum enzyme values were used in the following calculations. No significant difference was found between the maximum enzyme values in men and women or between younger and older patients (17). Thus no allowance has been made in the calculations for age or sex. FOIIOW-UP The patients were followed up on Jan. 1st 1973. The minimum period of observation was 12 months, the maximum 38 months. Information regarding the patients was Ar cent
survivors
1 )____. CPK.
40
i* Y
CPU ? 1 . 5 4
,m ‘l4
0
(M .? (0
f
,
bl
I
2
3
I, C P X . 9 I . CPK z i
Olservafion fimc ,n years
Fig. 1 . Survival curves of patients alive one month after first myocardial infarction, according to maximum values of CPK. Acta med. scand. 199
LDH ‘ i . 8 0 0
*---- lo“
= i. a 0 0 1,’ 1’1
f
#I
++ 2
Observation fime
, I
,. I.
‘08.I
U“.i
3 in ywm
F;g. 2 . Survival curves of patients alive one month after first myocardial infarction, according to maximum values of LDH.
obtained from hospital records, National Registration Offices, general practitioners, Medical Officers of Health and the Central Register of Deaths of the National Health Service. Of the 342 patients, 339 were traced. The remaining 3 were foreigners, who had been visiting this country; all three were discharged alive. Statistical analysis The actuarial method has been employed in the calculation of survival probability (3). Confidence limits of 95% have been used in the survival curves. The standard deviation has been calculated with the ”Greenwood’s estimate”. Statistical comparison between the survival rates has been carried out partly by evaluation of the curves with safety intervals and partly using the 2xnx2 test, where n is the number of observatior? intervals (1). For p
