569 PREVENTION OF CORONARY HEART-DISEASE Sm—In July the Department of Health circulated all doctors with the recommendations of a joint working-party of the Royal College of Physicians and the British Cardiac Society on the Prevention of Coronary Heart Disease. This official endorsement is astonishing. The main recommendation was to lower plasma-cholesterol by reducing saturated animal and dairy fat in the diet. In your columns two years ago,Iemphasised the uncertainty about this recommendation, and I am now even more convinced, from the arguments then presented and from further advances, that there can be little benefit on coronary incidence from such measures. The joint report is narrowly based on epidemiological studies and has ignored relevant and direct observational studies of high significance in this important and complex pathological process.
(1) Examination of living coronary arteries by angiography2 shows no difference in the severity of coronary-artery disease between patients with high and those with normal lipid values. Indeed Fuster et al.2 reported that "stepwise discriminant analysis revealed that no combination of the three coronary risk factors (smoking, hypertension and cholesterol) had any influence on the cardiographic patterns".
(2) An American controlled study3 in 834 patients on clofibrate and/or niacin which reduce plasma-cholesterol very significantly showed that these drugs had no beneficial influence coronary mortality.
on
(3) Werko has done a critical analysis. of the Framingham and other reports, finding a number of disturbing defects and discrepancies. He also points out the lack of any linear relationship of cholesterol levels with coronary manifestations in the published charts (figs. 7 and 8) in the Seven Countries study.’ Statistical correlation carries no conviction as a causeand-effect relationship and indeed the correlation is hardly significant if we exclude the figures for the East Finns (see [4] below). Björck,6 having given these matters the most detailed consideration over many years, was also highly sceptical about risk factors. (4) Punsar and Kamoven7 in their careful follow-up have shown that the higher coronary mortality in East Finland is due to the strenuous work of lumberjacks and not to cholesterollevels which were equally high in West Finland where the coronary death-rate is half. Dr Donald Gregg reported to the recent European Congress of Cardiology that when the coronary flow in dogs is reduced to a critical level exercise can precipitate infarction. In your editorial
(Aug. 28, p. 449)
you
comment
that in pa-
tients with atypical E.C.G.S who develop infarcts subsequently serum-cholesterol was not important. Indeed we all have a degree of coronary atheroma after about age 30. It is only the accidental complications that matter.
Many other points in the joint report deserve critical re-examination. It is better to trust to luck than to foster neurosis by pretence that we can save lives by interfering with life habits. Much of the advice is good general advice, but coronary disablement and mortality are unlikely to be changed. The Department of Health to its credit did not recommend the substitution of animal fats by polyunsaturated margarine. 2 Sorth Square, London XW11I
JOHN MCMICHAEL
1. 2.
McMichael, J. Lancet, 1974, i, 1340. Fuster, V., Frye, R. L., Connolly, D. C., Danielson, M. A., Elveback, L. R., Kurland, L. T. Br. Heart. J. 1975, 37, 1250. 3. Coronary Drug Project. J. Am. med. Ass. 1975, 231, 360. 4 Werkö, L. Am. Heart J. 1976, 91, 87. 5. International Co-operative Study on the Epidemiology of Cardiovascular Disease. Circulation, 1970, 42. 6. Björck, G. Contrasting Concepts of Ischæmic Heart Disease. Lilly Lectures
of 1974, Stockholm,
1975.
7. Punsar, S., Karvonen, M. J. in Paavo Nurmi Symposium. Basle, 1975.
UNRECOGNISED MYOCARDIAL INFARCTION
SIR,-You state (Aug. 28, p. 449) that "American and Israeli studies suggest that for every clinical infarct detected there is probably at least one unrecognised one in the same population". The number of unrecognised infarcts is obtained from the discovery Of E.C.G. changes thought to indicate infarction in those without symptoms or with atypical symptoms. This leaves out of account those unrecognised infarcts which do not cause E.c.G. changes. For there is no evidence whatsoever to support the commonly made assertion that all infarcts cause E.c.G. changes. The true figure of unrecognised infarcts is probably many times greater than you suggest. You ask: "Should one take frequent E.c.G.s for vague or suspicious symptoms, particularly in those with known risk factors... ?" The one good reason for taking frequent E.C.G.s-or for doing any other investigations-is to benefit the patient. Not so long ago the man who was thought to have the smallest infarct was put to bed for 6 weeks or so, initially at "absolute rest", and advised to live a restricted life thereafter. His brother who was seen by a doctor who did not do an E.c.G. and diagnosed "indigestion" was fortunate indeed to escape that appalling fate. Today, patients with minor infarcts are not treated so abominably, but even if a man is told no more than that he has had a minor infarct and encouraged to carry on living normally he and his wife and family will at the very least be worried. The taking of routine E.C.G.S on the middle-aged male population, which is so common in America and increasingly common in the U.K., is one of the most fatuous aspects of modem medicine. For a normal 12-lead E.c.G. can be found in someone with actual symptoms of myocardial ischaemia, and the finding of an abnormal E.c.. rarely if ever benefits the patient; it merely causes him anxiety. You end your editorial by urging "an attempt at prevention" of coronary heart-disease (C.H.D.). If the public would give up smoking, exercise vigorously throughout life, and not become obese the incidence of many maladies, including C.H.D., would drop. But all this has nothing to do with the taking of vast numbers of E.c.G.s. Vicarage Hill, Farnham, Surrey GU9 8HJ
6
JOHN W., TODD
ELISA: A REPLACEMENT FOR RADIOIMMUNOASSAYS? on the future of radioimmunoassay of timely. Many your readers, aware of the prominence of R.I.A., yet conscious of much discussion of the development of analogous analytical techniques which do without radioactivity, are probably confused about the future of analytical methods and about the way investment in instrumentation and expertise should be directed. Nevertheless I feel that you misrepresent the situation and point too unequivocally to trends which are by no means certain. Radioimmunoassay revolutionised the measurement of biologically important compounds because it combined the structural specificity of specific antibodies (and of other comparable, biologically derived binding reagents) with the sensitivity of radioactive measurement techniques. It adheres to the saturation-assay principle-i.e., a limited amount of a specific reagent (e.g., antibody) reacts with the substance under test and the extent of reaction of the test substance (some of which is labelled) reflects its concentration. An alternative approach uses similar reagents and measurement techniques though the principle is entirely different: an excess of specific reagent (e.g., antibody) is used and measurement is founded on the extent of reaction of the reagent with the test substance. This usually requires that the reagent itself should be labelled. Typical of this approach is the immunoradiometric assay of Miles and Hales. Each of these analytical principles has advantages and disadvantages with respect to
SIR,-Your editorial
was
the other; however, the
radioimmunoassay probably
became
(1) Examination of living coronary arteries by angiography2 shows no difference in the severity of coronary-artery disease between patients with high and those with normal lipid values. Indeed Fuster et al.2 reported that "stepwise discriminant analysis revealed that no combination of the three coronary risk factors (smoking, hypertension and cholesterol) had any influence on the cardiographic patterns".
(2) An American controlled study3 in 834 patients on clofibrate and/or niacin which reduce plasma-cholesterol very significantly showed that these drugs had no beneficial influence coronary mortality.
on
(3) Werko has done a critical analysis. of the Framingham and other reports, finding a number of disturbing defects and discrepancies. He also points out the lack of any linear relationship of cholesterol levels with coronary manifestations in the published charts (figs. 7 and 8) in the Seven Countries study.’ Statistical correlation carries no conviction as a causeand-effect relationship and indeed the correlation is hardly significant if we exclude the figures for the East Finns (see [4] below). Björck,6 having given these matters the most detailed consideration over many years, was also highly sceptical about risk factors. (4) Punsar and Kamoven7 in their careful follow-up have shown that the higher coronary mortality in East Finland is due to the strenuous work of lumberjacks and not to cholesterollevels which were equally high in West Finland where the coronary death-rate is half. Dr Donald Gregg reported to the recent European Congress of Cardiology that when the coronary flow in dogs is reduced to a critical level exercise can precipitate infarction. In your editorial
(Aug. 28, p. 449)
you
comment
that in pa-
tients with atypical E.C.G.S who develop infarcts subsequently serum-cholesterol was not important. Indeed we all have a degree of coronary atheroma after about age 30. It is only the accidental complications that matter.
Many other points in the joint report deserve critical re-examination. It is better to trust to luck than to foster neurosis by pretence that we can save lives by interfering with life habits. Much of the advice is good general advice, but coronary disablement and mortality are unlikely to be changed. The Department of Health to its credit did not recommend the substitution of animal fats by polyunsaturated margarine. 2 Sorth Square, London XW11I
JOHN MCMICHAEL
1. 2.
McMichael, J. Lancet, 1974, i, 1340. Fuster, V., Frye, R. L., Connolly, D. C., Danielson, M. A., Elveback, L. R., Kurland, L. T. Br. Heart. J. 1975, 37, 1250. 3. Coronary Drug Project. J. Am. med. Ass. 1975, 231, 360. 4 Werkö, L. Am. Heart J. 1976, 91, 87. 5. International Co-operative Study on the Epidemiology of Cardiovascular Disease. Circulation, 1970, 42. 6. Björck, G. Contrasting Concepts of Ischæmic Heart Disease. Lilly Lectures
of 1974, Stockholm,
1975.
7. Punsar, S., Karvonen, M. J. in Paavo Nurmi Symposium. Basle, 1975.
UNRECOGNISED MYOCARDIAL INFARCTION
SIR,-You state (Aug. 28, p. 449) that "American and Israeli studies suggest that for every clinical infarct detected there is probably at least one unrecognised one in the same population". The number of unrecognised infarcts is obtained from the discovery Of E.C.G. changes thought to indicate infarction in those without symptoms or with atypical symptoms. This leaves out of account those unrecognised infarcts which do not cause E.c.G. changes. For there is no evidence whatsoever to support the commonly made assertion that all infarcts cause E.c.G. changes. The true figure of unrecognised infarcts is probably many times greater than you suggest. You ask: "Should one take frequent E.c.G.s for vague or suspicious symptoms, particularly in those with known risk factors... ?" The one good reason for taking frequent E.C.G.s-or for doing any other investigations-is to benefit the patient. Not so long ago the man who was thought to have the smallest infarct was put to bed for 6 weeks or so, initially at "absolute rest", and advised to live a restricted life thereafter. His brother who was seen by a doctor who did not do an E.c.G. and diagnosed "indigestion" was fortunate indeed to escape that appalling fate. Today, patients with minor infarcts are not treated so abominably, but even if a man is told no more than that he has had a minor infarct and encouraged to carry on living normally he and his wife and family will at the very least be worried. The taking of routine E.C.G.S on the middle-aged male population, which is so common in America and increasingly common in the U.K., is one of the most fatuous aspects of modem medicine. For a normal 12-lead E.c.G. can be found in someone with actual symptoms of myocardial ischaemia, and the finding of an abnormal E.c.. rarely if ever benefits the patient; it merely causes him anxiety. You end your editorial by urging "an attempt at prevention" of coronary heart-disease (C.H.D.). If the public would give up smoking, exercise vigorously throughout life, and not become obese the incidence of many maladies, including C.H.D., would drop. But all this has nothing to do with the taking of vast numbers of E.c.G.s. Vicarage Hill, Farnham, Surrey GU9 8HJ
6
JOHN W., TODD
ELISA: A REPLACEMENT FOR RADIOIMMUNOASSAYS? on the future of radioimmunoassay of timely. Many your readers, aware of the prominence of R.I.A., yet conscious of much discussion of the development of analogous analytical techniques which do without radioactivity, are probably confused about the future of analytical methods and about the way investment in instrumentation and expertise should be directed. Nevertheless I feel that you misrepresent the situation and point too unequivocally to trends which are by no means certain. Radioimmunoassay revolutionised the measurement of biologically important compounds because it combined the structural specificity of specific antibodies (and of other comparable, biologically derived binding reagents) with the sensitivity of radioactive measurement techniques. It adheres to the saturation-assay principle-i.e., a limited amount of a specific reagent (e.g., antibody) reacts with the substance under test and the extent of reaction of the test substance (some of which is labelled) reflects its concentration. An alternative approach uses similar reagents and measurement techniques though the principle is entirely different: an excess of specific reagent (e.g., antibody) is used and measurement is founded on the extent of reaction of the reagent with the test substance. This usually requires that the reagent itself should be labelled. Typical of this approach is the immunoradiometric assay of Miles and Hales. Each of these analytical principles has advantages and disadvantages with respect to
SIR,-Your editorial
was
the other; however, the
radioimmunoassay probably
became
