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Uraemia and hyperuricaemia in acute myocardial infarction
45
Clinica Chimica Acta, 73 (1976) 45-50 0 Elsevier/North-Holland Biomedical Press
CGA 8024
URAEMIA AND HYPERURICAEMIA INFARCTION
IN ACUTE MYOCARDIAL
K. WIENER Department of Biochemistry, M8 6RB (U.K.) (Received
North Manchester General Hospital, Crumpsall, Manchester
March 31st, 1976)
Summary Plasma urate, urea and creatinine were measured at daily intervals for up to six days in 22 patients suffering from acute myocardial infarction. All except 3 patients showed some increase in plasma urea concentration and a tendency to increases in plasma urate was also observed. The increases in plasma urate correlated significantly with the increases in urea. This leads to the questioning of earlier reports linking hyperuricaemia with myocardial infarction when the possibility of uraemia has been ignored. Urine studies in a small number of patients showed no marked reduction in urea excretion, implying that increased production may partly account for the rise in plasma levels.
Introduction Several reports have appeared in which hyperuricaemia has been linked with atherosclerosis and myocardial infarction [l-4]. In fact, it has been suggested that hyperuricaemia may be considered to be a risk factor predisposing an individual to an increased susceptibility to coronary artery disease [5]. On the other hand, Myers et al. [6] found no evidence of such an association. A number of these studies have been carried out using blood specimens from patients already suffering from acute myocardial infarction and in some cases little attention seems to have been paid to the possibility of concurrent uraemia in these patients. In view of this, it was decided to investigate a smaller number of patients than in the previous studies, but to examine the individual subjects in greater detail. Methods Patients 22 male patients
were studied.
All were judged to be suffering
from acute
46
myocardial infarction on the basis of a characteristic clinical picture, electrocardiographic findings and raised plasma enzyme activity (aspartate aminotransferase, creatine kinase, lactate dehydrogenase). Diabetic patients were excluded from the study. 8 male subjects with myocardial ischaemia, but without signs of infarction, were also investigated as controls. These were cases admitted to hospital with chest pain and in whom there was electrocardiographic evidence of ischaemia, but not infarction, and plasma enzymes remained within normal limits. Sample
collection
Venous blood samples were collected into lithium heparin were made on the first day of admission to hospital and daily to 6 days. 24-h urine specimens were also collected from 7 infarction 3 patients with myocardial ischaemia. Again, collections were admission and continued for up to 6 days. Chemical
tubes. Collections thereafter, for up patients and from started soon after
analyses
Plasma and urine specimens were subjected to estimation of urea, creatinine and mate on a Technicon SMA multi-channel analyser. A diacetyl monoxime method was employed for urea, the Jaffe reaction for creatinine and a phosphotungstate method for urate. Details of the individual procedures were as recommended by the instrument manufacturer. The normal range for plasma urea was considered to be 2.5 to 7.5 mmol/l, for plasma creatinine 0.06 to 0.12 mmol/l and for plasma urate 0.17 to 0.48 mmol/l in males. Results Plasma urea 11 of the 22 patients
with acute myocardial infarction (50%) showed raised plasma urea during the study; 5 already had high levels at the start. In order to avoid the influence of any pre-existing renal disease, it was decided to exclude results from these 5 patients from the statistical calculations. Initial plasma urealevels in the 17 remaining subjects gave mean + S.D. of 5.18 + 1.32 mmol/l. In most cases, peak values occurred three or more days after admission to hospital and the mean + S.D. for these was 8.24 t 3.43 mmol/l. Only 3 patients showed no rise in plasma urea. The highest plasma urea levels recorded in the 8 control subjects gave a mean * S.D. of 5.71 + 1.29 mmol/l.
Plasma creatinine 9 of the 22 patients
(41%) had raised plasma creatinine during the study; 5 showed elevation at the start of the investigation. Means + S.D. for initial and peak plasma creatinine values in the 17 initially non-uraemic subjects were 0.101 + 0.022 mmol/l and 0.117 t 0.025 mmol/l, respectively. Corresponding figures for the highest plasma creatinine values in the controls were 0.103 * 0.017 mmol/l.
Plasma ura te 7 of the 22 patients (32%) had an abnormally high plasma urate at some time during the study; 5 had high levels at the start and all except one were associated with elevation of plasma urea and/or creatinine. 12 of the 17 initially non-uraemic patients exhibited some tendency to an increase in plasma urate concentration, but values usually remained within normal limits. Mean values for initial and maximal plasma urate in these 17 patients were 0.366 * 0.093 mmol/l and 0.414 f 0.100 mmol/l, respectively. Corresponding figures for the maximal values in the control subjects were 0.340 f 0.076 mmol/l. 4 infarction patients showed a slight fall in plasma urate concentration over the first two days of study; but there was a subsequent rise back to admission levels or higher within six days. Inter-relationships From the point of view of time scale, the rises in plasma urate, urea and creatinine tended to parallel each other in individual patients. In most cases, peak values occurred three of more days after admission to hospital. The initial and maximal values for all 22 patients are listed in Table I. Comparison of the observed increases in plasma urate with those of urea resulted in a significant positive correlation between the two constituents (r = 0.8231; P < 0.001). Significant positive correlations were also observed between increases in plasma urate and creatinine (r = 0.6139; P < 0.01) and between increases in plasma urea and creatinine (r = 0.5734; P < 0.05).
TABLE1 RESULTSOFPLASMAESTIMATIONSINTHE22MYOCARDIALINFARCTIONPATIENTS Patient
Initial values(mmol/l) Urate
1 2 3 4 5 6 1 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
0.31 0.32 0.31 0.24 0.51 0.25 0.41 0.31 0.30 0.34 0.48 0.53 0.48 0.33 0.28 0.45 0.31 0.54 0.51 0.40 0.23 0.49
Urea 5.0 4.5 3.8 4.0 5.3 3.0 6.3 5.5 4.7 5.7 3.0 6.7 7.5 4.5 5.2 6.7 6.7 21.0 11.0 10.5 10.2 9.0
Maximalvalues(mmol/l) Creatinine
Urate
Urea
Creatinine
0.11 0.12 0.07 0.06 0.09 0.08 0.11 0.10 0.10 0.10 0.10 0.14 0.13 0.09 0.07 0.12 0.09 0.36 0.21 0.12 0.12 0.13
0.38 0.32 0.52 0.29 0.51 0.25 0.48 0.38 0.34 0.35 0.48 0.61 0.48 0.50 0.31 0.48 0.36 0.74 * 0.67 0.42 0.26 0.52
6.5 6.0 14.2 6.3 5.5 5.0 11.3 9.0 6.5 5.1 4.7 11.8 7.5 11.5 5.2 7.5 15.8 32.7 20.3 20.5 10.2 12.0
0.11 0.12 0.16 0.09 0.11 0.10 0.14 0.13 0.12 0.10 0.12 0.17 0.13 0.10 0.07 0.12 0.09 0.45 0.21 0.16 0.12 0.14
4x
TABLE RESULTS
II OF URINE
MEASUREMENTS
IN THE TIIREE
PATIENT
GROIJI’S
Group 1, myocardial ischaemia without infarction; Group 2, infarction with normal plasma creatinine: Group 3, infarction with raised plasma urea and creatinine. ..__.____~___.. .--.._-. -_ -___ Patient groups
Group 1 Group 2 Group 3
Mean 24-h excretion -____-lll24-h urine volume (1)
Urak (mm&/24
1.506 1.472 1.061
3.90 5.25 4.07
h)
Urea (mm&/24 353 359 384
Creatinine clearance (ml/min)
____
--__. h)
Creatinine (mmo1/24 11.6 12.8 10.1
urea and
hf 95 111 63
Urine findings The 10 patients on whom urine measurements were made were divided into three groups : 1. Myocardial ischaemia without infarction (3 cases). 2. Infarction with normal plasma urea and creatinine (3 cases). 3. Infarction with raised plasma urea and creatinine (4 cases). Mean daily urea, creatinine and mate excretion for each patient group, together with creatinine clearance values, are shown in Table II. The third group exhibited a slightly higher mean daily urea excretion than the other groups; but this was accounted for by a particularly high excretion (558 mmol/24 h) in one patient. On the other hand, creatinine clearance and creatinine output was lower in this group with raised plasma levels. Urate excretion was very similar in Groups 1 and 3, but higher in Group 2. None of the patients in Groups 1 and 2 exhibited raised plasma urate at any time during the investigation. However, two patients in Group 3 did have raised plasma levels (0.52 mmol/l in both cases), one of whom also showed high urate excretion (5.58 mmol/24 h) and was the patient with the particularly high urea output. A third subject in Group 3 had a plasma urate concentration at the upper limit of normal. Discussion The results presented show that plasma urea frequently rises after myocardial infarction and may exceed the upper limit of normal. A less obvious rise in plasma urate was also seen and this correlated positively with the rise in urea, suggesting a relationship between them and introducing a complicating factor into the interpretation of previous reports linking myocardial infarction with hyperuricaemia per se. Uraemia could result from acute renal failure, but this is likely to occur in only a very small number of cases. However, a temporary or in some cases permanent reduction in the rate of renal blood flow could result from hypotension and shock, or possibly reduced cardiac output by the damaged heart. Alternatively, increased urea production could account for raised plasma levels, in spite of an associated increase in urinary excretion. An obvious source is breakdown
49
of necrosed cardiac tissue; however, complete breakdown of the heart would account for a theoretical rise in plasma urea of only 10 mmol/l, assuming free distribution throughout the body water. Since the extent of tissue damage would never be as great as this, it is unlikely that myocardial tissue breakdown could be responsible for the considerable rises in urea sometimes seen; but it may be a contributory factor. Although the urine studies were too small in number to allow unequivocal conclusions to be drawn, urea output did not appear to be low in either group of infarction patients, in spite of reduced creatinine clearance in those with raised plasma urea and creatinine levels. In fact, the subject with the highest urea output had a creatinine clearance of 75 ml/min and experienced left ventricular failure in the early stages of his illness. Increased urea formation has previously been reported in congestive heart failure, producing quite considerably uraemia in some cases [7]; muscle hypoxia is considered to be the cause. Similarly, other authors have suggested that stagnant tissue anoxia may be responsible for the muscle wasting sometimes seen in congestive cardiac failure [8]. In acute myocardial infarction, body protein catabolism will also be favoured by reduced food intake, elevated plasma corticosteroids [ 91, and temporary insulin deficiency [lo]. McEwin et al. [ 51 and Jacobs [4] found higher serum urate levels in myocardial infarction cases compared with normal subjects. In the former study, more than one determination was performed on most patients and a mean value taken, which according to the authors “helped to balance the day to day fluctuations”. In the other study, samples were collected on the fourth day after admission to hospital, which is about the time of peak values in the present study. Srivastava et al. [ll] found initial levels to be highest, with a subsequent fall continuing up to the fourth week, whereas Mikus [12] observed a fall in plasma urate over the first three days following infarction, with a return to admission levels by about the seventh day. This decline was attributed to increased adrenocortical activity at that stage of the condition and could explain the transient fall in plasma urate in four patients in the present study and, to some extent, the relatively high urate excretion in some of the infarction cases compared with the ischaemic ones, since cortisol has a uricosuric effect. Plasma and urine urate levels are affected by diet; but assuming this is constant, the plasma level would normally be determined by the rate of synthesis and degradation of purines within the body, together with excretion into the alimentary tract and in the urine. Following myocardial infarction, breakdown of damaged cardiac tissue would involve some purine degradation, and if there is also breakdown of other hypoxic muscle tissue, then this too is a potential source of urate. The existence of an enlarged urate pool and increased urate turnover has been demonstrated in myocardial infarction patients [13] and attributed to altered feedback control of purine synthesis. In addition, the diminished creatinine clearance seen in some of the patients of the present study suggests that reduced renal perfusion may be a significant factor in the aetiology of the rise in plasma urate. Diuretic therapy can also produce hyperuricaemia and some of the patients in this investigation were treated with diuretics. However, a recent study of myocardial infarction cases showed that diuretic therapy could account for only a part of the rise in plasma urate [14]. These authors re-
50
ported a significant positive correlation between plasma urate and creatinine and suggested that renal factors may have played a major role in the hyperuricaemia. The evidence presented indicates that a rise in plasma urea frequently occurs in acute myocardial infarction and a rise in plasma urate may accompany this; but hyperuricaemia in the absence of uraemia is unusual. Increased production or decreased excretion may be responsible for both and may result from circulatory impairment following infarction. It is likely that both factors play a part. This suggests that previous attempts to implicate hyperuricaemia as a risk factor for coronary disease may have been falsely based if patients already suffering from myocardial infarction were used to obtain data. Acknowledgement I should like to express my gratitude to the physicians of North Manchester General Hospital for allowing me to study their patients and also to the nursing and other staff who assisted in collection and handling of specimens. References 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Gertler, M.M., Garn. S.M. and Levine, S.A. (1951) Ann. Intern. Med. 34,1421-1431 Spring, M., Cavusoglu, M., Chu. Y.C. and Artymowska. E. (1960) Circulation 22, 817 Hall, A.P. (1965) Arthritis Rheum. 8.846-852 Jacobs, D. (1972) S. Afr. Med. J. 46. 367-369 McEwin, R., McEwin, K. and Loudon, B. (1974) Med. J. Aust. 1, 530-532 Myers. A.R., Epstein, F.H., Dodge, H.J. and Mikkelsen, W.M. (1968) Am. J. Med. 45, 520-528 Domenet, J.G. and Evans, D.W. (1969) Q. J. Med. 38.117-133 Pittman, J.G. and Cohen, P. (1964) N. Engl. J. Med. 271.453-460 Logan, R.W. and Murdoch, W.R. (1966) Lane& ii, 521-524 Allison, S.P., Chamberlain, M.J. and Hinton, P. (1969) Br. Med. J. 4, 776-778 Srivastava, B.N.. Hari, O.M., Deshmankar, B.S. and Gupta, R.K. (19’74) Ind. Heart J. 26, 24-28 MikuH, F. (1972) Beitr. RheumatoI. 18, 74-76 Dosman, J.A., Crawhall, J.C. and Klassen, G.A. (1975) Metabolism 24.473-480 Ghosh, P., Cochrane, A.M.G., Gordon, P.W.N. and Radcliffe, A.G. (1975) Br. Med. J. 4, 261--262
Clinica Chimica Acta, 73 (1976) 45-50 0 Elsevier/North-Holland Biomedical Press
CGA 8024
URAEMIA AND HYPERURICAEMIA INFARCTION
IN ACUTE MYOCARDIAL
K. WIENER Department of Biochemistry, M8 6RB (U.K.) (Received
North Manchester General Hospital, Crumpsall, Manchester
March 31st, 1976)
Summary Plasma urate, urea and creatinine were measured at daily intervals for up to six days in 22 patients suffering from acute myocardial infarction. All except 3 patients showed some increase in plasma urea concentration and a tendency to increases in plasma urate was also observed. The increases in plasma urate correlated significantly with the increases in urea. This leads to the questioning of earlier reports linking hyperuricaemia with myocardial infarction when the possibility of uraemia has been ignored. Urine studies in a small number of patients showed no marked reduction in urea excretion, implying that increased production may partly account for the rise in plasma levels.
Introduction Several reports have appeared in which hyperuricaemia has been linked with atherosclerosis and myocardial infarction [l-4]. In fact, it has been suggested that hyperuricaemia may be considered to be a risk factor predisposing an individual to an increased susceptibility to coronary artery disease [5]. On the other hand, Myers et al. [6] found no evidence of such an association. A number of these studies have been carried out using blood specimens from patients already suffering from acute myocardial infarction and in some cases little attention seems to have been paid to the possibility of concurrent uraemia in these patients. In view of this, it was decided to investigate a smaller number of patients than in the previous studies, but to examine the individual subjects in greater detail. Methods Patients 22 male patients
were studied.
All were judged to be suffering
from acute
46
myocardial infarction on the basis of a characteristic clinical picture, electrocardiographic findings and raised plasma enzyme activity (aspartate aminotransferase, creatine kinase, lactate dehydrogenase). Diabetic patients were excluded from the study. 8 male subjects with myocardial ischaemia, but without signs of infarction, were also investigated as controls. These were cases admitted to hospital with chest pain and in whom there was electrocardiographic evidence of ischaemia, but not infarction, and plasma enzymes remained within normal limits. Sample
collection
Venous blood samples were collected into lithium heparin were made on the first day of admission to hospital and daily to 6 days. 24-h urine specimens were also collected from 7 infarction 3 patients with myocardial ischaemia. Again, collections were admission and continued for up to 6 days. Chemical
tubes. Collections thereafter, for up patients and from started soon after
analyses
Plasma and urine specimens were subjected to estimation of urea, creatinine and mate on a Technicon SMA multi-channel analyser. A diacetyl monoxime method was employed for urea, the Jaffe reaction for creatinine and a phosphotungstate method for urate. Details of the individual procedures were as recommended by the instrument manufacturer. The normal range for plasma urea was considered to be 2.5 to 7.5 mmol/l, for plasma creatinine 0.06 to 0.12 mmol/l and for plasma urate 0.17 to 0.48 mmol/l in males. Results Plasma urea 11 of the 22 patients
with acute myocardial infarction (50%) showed raised plasma urea during the study; 5 already had high levels at the start. In order to avoid the influence of any pre-existing renal disease, it was decided to exclude results from these 5 patients from the statistical calculations. Initial plasma urealevels in the 17 remaining subjects gave mean + S.D. of 5.18 + 1.32 mmol/l. In most cases, peak values occurred three or more days after admission to hospital and the mean + S.D. for these was 8.24 t 3.43 mmol/l. Only 3 patients showed no rise in plasma urea. The highest plasma urea levels recorded in the 8 control subjects gave a mean * S.D. of 5.71 + 1.29 mmol/l.
Plasma creatinine 9 of the 22 patients
(41%) had raised plasma creatinine during the study; 5 showed elevation at the start of the investigation. Means + S.D. for initial and peak plasma creatinine values in the 17 initially non-uraemic subjects were 0.101 + 0.022 mmol/l and 0.117 t 0.025 mmol/l, respectively. Corresponding figures for the highest plasma creatinine values in the controls were 0.103 * 0.017 mmol/l.
Plasma ura te 7 of the 22 patients (32%) had an abnormally high plasma urate at some time during the study; 5 had high levels at the start and all except one were associated with elevation of plasma urea and/or creatinine. 12 of the 17 initially non-uraemic patients exhibited some tendency to an increase in plasma urate concentration, but values usually remained within normal limits. Mean values for initial and maximal plasma urate in these 17 patients were 0.366 * 0.093 mmol/l and 0.414 f 0.100 mmol/l, respectively. Corresponding figures for the maximal values in the control subjects were 0.340 f 0.076 mmol/l. 4 infarction patients showed a slight fall in plasma urate concentration over the first two days of study; but there was a subsequent rise back to admission levels or higher within six days. Inter-relationships From the point of view of time scale, the rises in plasma urate, urea and creatinine tended to parallel each other in individual patients. In most cases, peak values occurred three of more days after admission to hospital. The initial and maximal values for all 22 patients are listed in Table I. Comparison of the observed increases in plasma urate with those of urea resulted in a significant positive correlation between the two constituents (r = 0.8231; P < 0.001). Significant positive correlations were also observed between increases in plasma urate and creatinine (r = 0.6139; P < 0.01) and between increases in plasma urea and creatinine (r = 0.5734; P < 0.05).
TABLE1 RESULTSOFPLASMAESTIMATIONSINTHE22MYOCARDIALINFARCTIONPATIENTS Patient
Initial values(mmol/l) Urate
1 2 3 4 5 6 1 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
0.31 0.32 0.31 0.24 0.51 0.25 0.41 0.31 0.30 0.34 0.48 0.53 0.48 0.33 0.28 0.45 0.31 0.54 0.51 0.40 0.23 0.49
Urea 5.0 4.5 3.8 4.0 5.3 3.0 6.3 5.5 4.7 5.7 3.0 6.7 7.5 4.5 5.2 6.7 6.7 21.0 11.0 10.5 10.2 9.0
Maximalvalues(mmol/l) Creatinine
Urate
Urea
Creatinine
0.11 0.12 0.07 0.06 0.09 0.08 0.11 0.10 0.10 0.10 0.10 0.14 0.13 0.09 0.07 0.12 0.09 0.36 0.21 0.12 0.12 0.13
0.38 0.32 0.52 0.29 0.51 0.25 0.48 0.38 0.34 0.35 0.48 0.61 0.48 0.50 0.31 0.48 0.36 0.74 * 0.67 0.42 0.26 0.52
6.5 6.0 14.2 6.3 5.5 5.0 11.3 9.0 6.5 5.1 4.7 11.8 7.5 11.5 5.2 7.5 15.8 32.7 20.3 20.5 10.2 12.0
0.11 0.12 0.16 0.09 0.11 0.10 0.14 0.13 0.12 0.10 0.12 0.17 0.13 0.10 0.07 0.12 0.09 0.45 0.21 0.16 0.12 0.14
4x
TABLE RESULTS
II OF URINE
MEASUREMENTS
IN THE TIIREE
PATIENT
GROIJI’S
Group 1, myocardial ischaemia without infarction; Group 2, infarction with normal plasma creatinine: Group 3, infarction with raised plasma urea and creatinine. ..__.____~___.. .--.._-. -_ -___ Patient groups
Group 1 Group 2 Group 3
Mean 24-h excretion -____-lll24-h urine volume (1)
Urak (mm&/24
1.506 1.472 1.061
3.90 5.25 4.07
h)
Urea (mm&/24 353 359 384
Creatinine clearance (ml/min)
____
--__. h)
Creatinine (mmo1/24 11.6 12.8 10.1
urea and
hf 95 111 63
Urine findings The 10 patients on whom urine measurements were made were divided into three groups : 1. Myocardial ischaemia without infarction (3 cases). 2. Infarction with normal plasma urea and creatinine (3 cases). 3. Infarction with raised plasma urea and creatinine (4 cases). Mean daily urea, creatinine and mate excretion for each patient group, together with creatinine clearance values, are shown in Table II. The third group exhibited a slightly higher mean daily urea excretion than the other groups; but this was accounted for by a particularly high excretion (558 mmol/24 h) in one patient. On the other hand, creatinine clearance and creatinine output was lower in this group with raised plasma levels. Urate excretion was very similar in Groups 1 and 3, but higher in Group 2. None of the patients in Groups 1 and 2 exhibited raised plasma urate at any time during the investigation. However, two patients in Group 3 did have raised plasma levels (0.52 mmol/l in both cases), one of whom also showed high urate excretion (5.58 mmol/24 h) and was the patient with the particularly high urea output. A third subject in Group 3 had a plasma urate concentration at the upper limit of normal. Discussion The results presented show that plasma urea frequently rises after myocardial infarction and may exceed the upper limit of normal. A less obvious rise in plasma urate was also seen and this correlated positively with the rise in urea, suggesting a relationship between them and introducing a complicating factor into the interpretation of previous reports linking myocardial infarction with hyperuricaemia per se. Uraemia could result from acute renal failure, but this is likely to occur in only a very small number of cases. However, a temporary or in some cases permanent reduction in the rate of renal blood flow could result from hypotension and shock, or possibly reduced cardiac output by the damaged heart. Alternatively, increased urea production could account for raised plasma levels, in spite of an associated increase in urinary excretion. An obvious source is breakdown
49
of necrosed cardiac tissue; however, complete breakdown of the heart would account for a theoretical rise in plasma urea of only 10 mmol/l, assuming free distribution throughout the body water. Since the extent of tissue damage would never be as great as this, it is unlikely that myocardial tissue breakdown could be responsible for the considerable rises in urea sometimes seen; but it may be a contributory factor. Although the urine studies were too small in number to allow unequivocal conclusions to be drawn, urea output did not appear to be low in either group of infarction patients, in spite of reduced creatinine clearance in those with raised plasma urea and creatinine levels. In fact, the subject with the highest urea output had a creatinine clearance of 75 ml/min and experienced left ventricular failure in the early stages of his illness. Increased urea formation has previously been reported in congestive heart failure, producing quite considerably uraemia in some cases [7]; muscle hypoxia is considered to be the cause. Similarly, other authors have suggested that stagnant tissue anoxia may be responsible for the muscle wasting sometimes seen in congestive cardiac failure [8]. In acute myocardial infarction, body protein catabolism will also be favoured by reduced food intake, elevated plasma corticosteroids [ 91, and temporary insulin deficiency [lo]. McEwin et al. [ 51 and Jacobs [4] found higher serum urate levels in myocardial infarction cases compared with normal subjects. In the former study, more than one determination was performed on most patients and a mean value taken, which according to the authors “helped to balance the day to day fluctuations”. In the other study, samples were collected on the fourth day after admission to hospital, which is about the time of peak values in the present study. Srivastava et al. [ll] found initial levels to be highest, with a subsequent fall continuing up to the fourth week, whereas Mikus [12] observed a fall in plasma urate over the first three days following infarction, with a return to admission levels by about the seventh day. This decline was attributed to increased adrenocortical activity at that stage of the condition and could explain the transient fall in plasma urate in four patients in the present study and, to some extent, the relatively high urate excretion in some of the infarction cases compared with the ischaemic ones, since cortisol has a uricosuric effect. Plasma and urine urate levels are affected by diet; but assuming this is constant, the plasma level would normally be determined by the rate of synthesis and degradation of purines within the body, together with excretion into the alimentary tract and in the urine. Following myocardial infarction, breakdown of damaged cardiac tissue would involve some purine degradation, and if there is also breakdown of other hypoxic muscle tissue, then this too is a potential source of urate. The existence of an enlarged urate pool and increased urate turnover has been demonstrated in myocardial infarction patients [13] and attributed to altered feedback control of purine synthesis. In addition, the diminished creatinine clearance seen in some of the patients of the present study suggests that reduced renal perfusion may be a significant factor in the aetiology of the rise in plasma urate. Diuretic therapy can also produce hyperuricaemia and some of the patients in this investigation were treated with diuretics. However, a recent study of myocardial infarction cases showed that diuretic therapy could account for only a part of the rise in plasma urate [14]. These authors re-
50
ported a significant positive correlation between plasma urate and creatinine and suggested that renal factors may have played a major role in the hyperuricaemia. The evidence presented indicates that a rise in plasma urea frequently occurs in acute myocardial infarction and a rise in plasma urate may accompany this; but hyperuricaemia in the absence of uraemia is unusual. Increased production or decreased excretion may be responsible for both and may result from circulatory impairment following infarction. It is likely that both factors play a part. This suggests that previous attempts to implicate hyperuricaemia as a risk factor for coronary disease may have been falsely based if patients already suffering from myocardial infarction were used to obtain data. Acknowledgement I should like to express my gratitude to the physicians of North Manchester General Hospital for allowing me to study their patients and also to the nursing and other staff who assisted in collection and handling of specimens. References 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Gertler, M.M., Garn. S.M. and Levine, S.A. (1951) Ann. Intern. Med. 34,1421-1431 Spring, M., Cavusoglu, M., Chu. Y.C. and Artymowska. E. (1960) Circulation 22, 817 Hall, A.P. (1965) Arthritis Rheum. 8.846-852 Jacobs, D. (1972) S. Afr. Med. J. 46. 367-369 McEwin, R., McEwin, K. and Loudon, B. (1974) Med. J. Aust. 1, 530-532 Myers. A.R., Epstein, F.H., Dodge, H.J. and Mikkelsen, W.M. (1968) Am. J. Med. 45, 520-528 Domenet, J.G. and Evans, D.W. (1969) Q. J. Med. 38.117-133 Pittman, J.G. and Cohen, P. (1964) N. Engl. J. Med. 271.453-460 Logan, R.W. and Murdoch, W.R. (1966) Lane& ii, 521-524 Allison, S.P., Chamberlain, M.J. and Hinton, P. (1969) Br. Med. J. 4, 776-778 Srivastava, B.N.. Hari, O.M., Deshmankar, B.S. and Gupta, R.K. (19’74) Ind. Heart J. 26, 24-28 MikuH, F. (1972) Beitr. RheumatoI. 18, 74-76 Dosman, J.A., Crawhall, J.C. and Klassen, G.A. (1975) Metabolism 24.473-480 Ghosh, P., Cochrane, A.M.G., Gordon, P.W.N. and Radcliffe, A.G. (1975) Br. Med. J. 4, 261--262