449

THE LANCET

Unrecognised Myocardial

Infarction

IN cardiovascular disease the epidemiological approach-concerned with the distribution and determinants of disease in defined populations-has yielded much information concerning the natural history of coronary heart-disease (C.H.D.). Most cardiologists now accept that there is a wider world of disease beyond the wards and the clinics, and that data based on those patients who reach hospital do not truly reflect the pattern of a disease. In the United Kingdom the studies of myocardial infarction in Oxford,l Edinburgh,2 and London (Tower Hamlets)3 have clearly shown the limitations of the view from the hospital. Most C.H.D. events have their onset at home and most deaths occur at the place of onset. Most coronary deaths occurring in the first four weeks take place within one hour, and most of these within the first

few minutes. The

myocardial-infarction comnow spread very widely and munity registers the W.H.O. International Collaborative Study4 covered 19 countries in Europe together with Australia and Israel, and involved 3ymillion people aged 20-64 years. This report provides a remarkable view of myocardial infarction in the comhave

munity, since all persons, male or female, in whom "any suspicion" of acute myocardial infarction might have occurred, were admitted to the registers. But what of those in whom suspicion of a heart-attack has not arisen? The concept of painless myocardial infarction has been well-documented for over twenty years,5 but clinicians are still reluctant to accept "probable" or "possible" electrocardiographic evidence of myocardial infarction in the absence of any suggestive symptoms. Several prospective community studies in the United States have shown 1 Kinlen, L J. Br. Heart J. 1973, 35, 616.

that almost a third of infarcts are. unrecognised;67 about half of these are silent-i.e., there are no associated symptoms at all-whereas the other half 7 are symptomatic but with atypical complaints.’ The importance of unrecognised myocardial infarctions can only be assessed by determining (a) their relation to clinically obvious myocardial infarction, (b) the prognosis in those with unrecognised infarcts, and (c) the patterns of risk factors associated with their development. An Israeli report,8 based on the results of a prospective study of almost 10 000 men aged 40 years or more, answers some of these questions. The study population consisted of permanent Government and municipal employees, and the response to the initial (1963) examination was 86%, with 98% of those still living being re-examined in 1968. The mortality follow-up was 100% and was extended to 1970 (7 years). All those who in 1963 had E.C.G. evidence of myocardial infarction or leftbundle-branch block, or a suggestive history of infarct, were removed from those at risk, as were the subjects who had a clinical myocardial infarct (M.I.) between 1963 and 1968. In the remaining

subjects, unrecognised infarction

was

diagnosed

when the E.c.G. in 1965 or in the 1968 follow-up revealed evidence of M.I. and when no history or other evidence was obtained. Since E.c.G. evidence of M.I. can disappear, sometimes in as little as 6 months, the incidence rates based on 2 or 3 year intervals will considerably underestimate the "true" incidence. During the 5-year follow-up there were 427 infarcts, of which 170 (40%) were unrecognised. The rate rose steeply with age from 2-0/1000 persons in the 40-49 age group to 10-6/1000 in the 60-andover group, in keeping with the steep rise with age seen in clinical infarcts. Half of those with unrecognised infarcts had no recollection of any symptoms or illness ("silent"), while 40% had atypical symptoms which neither the patient nor the physician associated with a heart-attack. All E.C.G.S were recorded simultaneously on paper and on tape and the taped E.C.G.S were interpreted by computer. There was considerable disagreement between the computer and the project cardiologists, who did not accept the computer’s views of abnormality and re-interpreted all of them. Of the tracings interpreted by the computer as possible or probable infarcts, only 15% were accepted by the cardiologists as infarcts. The subjects diagnosed by computer as having infarcts and by the cardiologists as not having infarcts had a slightly higher rate of clinical M.l.s and a strikingly increased rate

2 Armstrong, A, Duncan, B., Oliver,

M. F., Julian, D. G., Donald, K. W., Fulton, M, Lutz, W., Morrison, S. ibid. 1972, 34, 67. 3 Tunstall Pedoe, H., Clayton, D. G., Morris, J. N., Brigden, W., McDonald, L Lancet, 1975, ii, 833.

4

World Health Organisation. Public Health tion

Community Registers. Regional

1976 5 Roseman, M. D. Ann.

intern.

Med.

in

Office

1954, 41,

Myocardial Infarcfor Europe, Copenhagen,

Europe

1.

5.

Rosenman, R. H., Fnedman, M., Straus, R., Jenkins, C. D., Zyzarski, S. J., Wurm, M. J. chron. Dis. 1970, 23, 173. 7. Marfolis, J. R., Kannel, W. B., Femleib, M., Dawber, T. R., McNamara, P. M. Am. J. Cardiol. 1973, 32, 1. 8. Medalie, J. H., Goldbourt, U. Ann. intern. Med. 1976, 84, 526.

6.

450

of unrecognised infarcts during the next 5 years. The computer thus turned out to be the best predictor of subsequent unrecognised infarcts. Multivariate analysis of the 5-year incidence of unrecognised infarctions revealed that the most significantly related variables were age, left-axis deviation and left-ventricular hypertrophy on E.C.G., cigarette smoking, blood-pressure, and peripheral vascular disease. Some of the known risk factors for clinical infarct or angina, such as serumcholesterol, diabetes, anxiety, and psychosocial pro-

blems,

were

not

important

in

unrecognised

in-

farcts. Over the

7-year follow-up for mortality, the general study population had an average annual mortality-rate of 4-6/1000, whereas those with unrecognised infarcts had almost 4 times this rate In those with overt clinical infarcts 75/1000, 4y times the rate of the unrecognised infarcts and 16 times the rate of the infarct-free section of the population. This observation is at variance with those at Framingham,7 where subjects with unrecognised infarcts had the same mortality as those with clinical infarcts, but the Israeli workers regard the Framingham results

(17-3/1000).

the rate

was

as possibly misleading, since fatal cases were excluded from analysis. The American and Israeli studies suggest that for every clinical infarct detected there is probably as least one unrecognised one in the same population. Apparently the unrecognised infarct is a less severe episode of myocardial ischaemia than the clinically overt infarction, with a lower 7-year mortality-rate. These findings raise a number of issues-notably, concerning screening of populations at risk. Should one take frequent E.c.G.s for vague or suspicious symptoms, particularly in those with known risk factors such as hypertension or diabetes mellitus? In societies high in the world league-table for C.H.D., the social and financial consequences of regular E.c.G. surveillance of all middle-aged subjects with one or more risk factors and/or minor symptoms are frightening to contemplate. Despite the lack of conclusive evidence that removal of risk factors reduces the incidence of c.H.D., an attempt at prevention9 seems the only way out of the present epidemic.

Clinical

Immunology

CLINICAL immunology has developed at a brisk pace, both academically and in relation to the practice of medicine, since the late 1950s; and those associated with it enjoy the intellectual stimulus of a subject where the basic physiology is unravelling, often with prompt application to the elucidation of 9. Joint Working Party of the Royal College of Physicians of London and the British Cardiac Society. Jl.R. Coll. Physns. 1976, 10, 213. 10. Roitt, I. M. Essential Immunology. Oxford, 1974.

disorders hitherto obstinately obscure. Thus, ideas on the pathogenesis of pernicious anaemia have moved from the contemplation of the drinking of too much hot tea to the picture of an organ-specific autoimmune process against the specialised cells of the mucosa of the body of the stomach and to the recognition that the condition is one of the family of organ-specific autoimmune diseases, whose members are mainly endocrine disorders including juvenile-onset diabetes." Immune complexes and antibody to glomerular basement members are important in the causation and diagnosis of different types of glomerulonephritis; 12 and allergic reactions are the underlying mechanism in certain hitherto unexplained lung diseases.13 Other examples abound of the application of immunology to

medicine. 14 The fuller understanding of the immunodeficiency disorders that has emerged from the better appreciation of the physiology of the immune system has led to remarkable therapeutic achievements. The role of plasma exchange in Goodpasture’s syndrome and other conditions is becoming established. Prevention of haemolytic disease of the newborn is now routine by means of immunological techniques; and there is hope that immuno-suppression may achieve greater specificity than has so far been possible. The association between certain HLA phenotypes and immune-response genes is yielding exciting evidence about the linkage between genetics and the behaviour of the immune system and susceptibility to disorders linked with immunopathology. Again the immune mechanisms which may cause tissue damage are being more closely defined. The rapid establishment of Clinical and Experimental Immunology as a major publication within the past ten years, the much stronger representation of basic and applied immunology in undergraduate and postgraduate texts,ls-1’ and the popularity of the clinical immunology course for physicians and scientists held in Edinburgh each year all testify to the growth of the subject, especially within the United Kingdom. All the references we have cited so far are to British work. Although it is perhaps un-British to talk of this country’s achievements in thisarea, it is the needs of the subject in Britain which are the theme of the article by Dr REEVES on p. 459 this week. His paper, which emanates from the British Society for Immunology’s working party on clinical immu11. Irvine, W.

J. (editor) Autoimmunity in Endocrine Disease; vol. 4, no 2, of Endocrinology. London, 1975. 12. Peters, D. K., Williams, D. C. in Recent Advances in Renal Disease, edited by N. F. Jones), Edinburgh, 1975. 13. Pepys, J., Turner-Warrick, M. in Clinical Aspects of Immunology; chap 43 (edited by P. H. Gell, R. R. A. Coombs, and P. J. Lachmann), Oxford Clinics

in

1975. 14. Gell, P. H., Coombs, R. R. A., Lachmann, P. J. (editors) ibid. 15. Macleod, J. (editor) Davidson’s Textbook of Medicine. Edinburgh, 1974 16. Passmore, R., Robson, J. S. (editors). Companion to Medical Studies; vols, I-III. Oxford, 1974-76. 17. Peters, D. K. (editor). Advanced Medicine: 12th symposium in Advanced Medicine. Royal College of Physicians, London, 1976.

Unrecognised myocardial infarction.

449 THE LANCET Unrecognised Myocardial Infarction IN cardiovascular disease the epidemiological approach-concerned with the distribution and deter...
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