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THE COAGULABILITY OF BLOOD INRELATION TO CORONARY HEART DISEASE

By C. MERSKEY, M.D.(Cape), M.R.C.P.(London)Senior Lecturer and Physician, Department of Medicine, Groote Schuur Hospital and University of Cape Town

and H. LACKNER, M.D.(Leeds), M.R.C.P.(London)Part-time Lecturer and Assistant Physician, Department of Medicine and Groote Schuur Hospital

It is generally agreed that atheroma of thecoronary artery, complicated by thrombosis ofthat vessel, is the usual cause of myocardial in-farction, but in some cases infarction can ap-parently occur without thrombosis. What partdoes coagulation of the blood play in coronaryartery disease? Is it important in the pathogenesisof atheroma-is it, for instance, one of the under-lying mechanisms in the production of the athero-matous plaque? How important is the actualformation of a thrombus in the coronary vessel inan acute infarct? What evidence is there thatalteration in blood coagulability plays a part in thedevelopment (or lack of development) of thedisease in an individual or a group of individuals?Is there a relationship between alterations in bloodlipids, which can occur normally or be broughtabout by dietary and other means, and demon-strable alterations in the blood coagulatingmechanisms?

If blood coagulation is important in some ofthese respects it might, for instance, lend addedsupport to the use of anticoagulants for theprevention of recurrent coronary thrombosis ormyocardial infarction. It would also justifyattempts to ensure prevention of the initial throm-bosis in people who, for reason of age, sex, familyhistory and the presence of recognizable athero-sclerosis in other parts of the body, might be re-garded as especially at risk of coronary thrombosis.If it could be shown, for example, that there is a

positive association between serum-cholesterollevels and liability to clot, this would provideadditional justification for attempting to lower theserum-cholesterol level in patients at risk whoseserum cholesterol is well above the mean for ageand sex. Methods for the reduction of serumcholesterol might include dietary manipulationand particularly the modification of the quantityand quality of the dietary fat.

For all these reasons there has been a surge ofinterest in the study of blood coagulability and the

mechanisms of coagulation and anticoagulation inrelation to the pressing problem of ischaemicheart disease. Conclusions at this stage must betentative and form the basis rather for further re-search than for immediate application.Thrombosis may act in two ways. In the first

place it may be responsible for intimal thickeningwhicfi could be the basis of the atheromatousplaque and, secondly, it could add to atheromaand so be part of the mechanism of final closureof the artery. Rokitansky (I84I) stated that thedeposit in the artery in atheroma is an endogenousproduct derived from the blood and for the mostpart from the fibrin of the original blood. Duguid(1946) revived and elaborated this theory, claimingthat a mural thrombus forming in an artery couldbecome covered with endothelium and, on sub-sequently becoming organized, form a fibrousthickening of the intima. Mural thrombi, heclaimed, especially of the red type, commonlyunderwent fatty change and assumed the charac-ters of atherosclerotic plaques. He believed thatthere was good evidence that a considerable pro-portion of the lesions classified as atherosclerosiswere altered thrombi (Duguid and Robertson,1957). Morgan (1956) and others also supportedthis view. Levene ('1955, I956) reported thatapparently collagenous plaques of intimal thicken-ing, when examined with the electron microscope,consisted mainly of fibrin. This could support thethrombogenic theory of atherogenesis, since it isnot easy to explain in any other way the presenceof fibrin in this situation. This explanation of thepathogenesis has not gone unchallenged (Keechand Reed, 1955; van den Hoof, 1955, 1956). It isalso conceivable that the fibrin is derived fromintimal haemorrhage which has been held to pre-cede the atheromatous plaques as has beenstressed by Paterson (1938) and others. Fewwould deny the importance of age and local strainor tension (Duguid, 1926; Muir, 195i). This iswell shown by the presence of atheroma around

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openings of the intercostal vessels in the aorta andthe greater amount of atheroma which developsin hypertension. But one cannot ignore thepresence of excess cholesterol and other lipids inthe blood and many would feel that these play amajor part in the production of atheroma for theyare, sooner or later, deposited in the artery. Thereis an associated local reaction with the productionof fibrous tissue and the atheromatous plaquedevelops. We would agree with this concept ofthe aetiology of atheroma; in it thrombosis wouldappear to play only a minor part.

While it is arguable that thrombosis is im-portant in the causation of atheroma it is not dis-puted that it is often the final step in the closure ofthe coronary artery. It is not always so. Levineand Brown (I929), for example, examined 44 casesof myocardial infarction and found 23 occludedby a definite thrombus while 12 showed narrowingwithout thrombosis. In a recent study, Branwoodand Montgomery (1956) found that 29 out of 6irecent infarcts had thrombi but only 13 of these(21 per cent.) were fully occlusive; in addition,occlusion by soft atheroma, by the breakdown ofan atheromatous patch, had occurred almost asfrequently. They considered that, by the usualhistological criteria it seemed that the thrombiwere not the cause but were a terminal event insome of these cases of infarction. Boyd (1953)lists the causes of coronary occlusion in order offrequency as: (i) atheroma, (2) haemorrhage intothe intima, (3) rupture of an atheromatous plaque,and (4) thrombosis. We believe that there are amultitude of factors operating; these have a vary-ing validity in different cases. A familial ten-dency, hypercholesterolaemia, and a variety oflocal factors appear to be concerned. Thrombosisagain only seems to play a small part in the initia-tion of the atheromatous plaque, but it is certainlypart of the mechanism of final closure of theartery.

While local abnormalities in the lumen of thevessel may provoke thrombosis it is less certainthat a generalized tendency to more rapid coagula-tion of the blood also plays a part. One of thedifficulties is that it is not easy to demonstratein vitro such a hypercoagulable state. The normalfluidity of the blood is determined by a delicatelybalanced mechanism and many factors could upsetthis balance and so predispose to thrombosis.Blood is especially liable to clot in vessels whoseendothelial surface is damaged by disease or whoselumen is diminished by the thickening of the wall.Stasis and slowing of the blood stream may beimportant factors in the precipitation of a throm-bus. In artificial tubular systems there arevariations in marginal flow when the channels aretortuous, angulated or of varying calibre (Rodbard,

I956). In a patient in whom enough unfavour-able circumstances coexist pathological thrombosismay occur (Biggs and Macfarlane, I957).

Certain conditions are notoriously associatedwith pathological thrombosis in veins, e.g. malig-nant disease, leukaemia, post-puerperal and post-operative states. If a state of increased co-agulability of the blood exists one might expect tobe able to show it in one or other of these condi-tions. Many authors claim to have shown an in-creased tendency of the blood to clot. It has beenasserted, for example, that patients who develop athrombus have a shortening of the whole blood-clotting time (Cummine and Lyons, 1948; Barkerand Margulies, 1949; Warren, I953); tests usingheparin in vivo or in vitro have been said to beabnormal (de Takats, 1943; Hagedorn andBarker, I948); ' fibrinogen B ' has been said to beincreased (Cummine and Lyons, 1948). All theseclaims have been denied (Ingram, Biggs andArmitage, I953; Paterson and McLachlin, 1954).Hum, Barker and Mann (1947) were unable tofind a consistent variation in prothrombin or anti-thrombin in patients with thrombosing tendencieswhen compared with normal.

It has been claimed that patients with acutemyocardial infarction may have phases duringwhich the blood changes from a hypercoagulablestate through a phase of reduced coagulability toreach a stage of late hypercoagulability (Beaumont,Chevalier and Lenegre, I953). Alternatively,patients with acute myocardial infarction could besubdivided into those with evidence of acceleratedcoagulation, those with normal coagulation andthose with retarded coagulation. Anticoagulanttherapy would then only be given to those in whomthe blood showed increased coagulation (FitzgeraldPeel, 1956).A rise in platelet count occurs post-operatively

and post-puerperally as does increased plateletstickiness (Wright, 1942); Moolton and co-workers (I949a, i949b) also claimed an increasedplatelet stickiness after cellular destruction insurgery, after trauma or after acute myocardialinfarction and peripheral gangrene. This was notconfirmed by others (Eisen, Tyson, Michael andBaumann, 195i). De Nicola (1953) claimed anincrease in factor 7 in thromboembolic disease andin late pregnancy, the latter finding also being re-ported by Koller (i954) and Alexander (1955), butthere is little evidence that the increase in thisfactor has anything to do with an increased ten-dency to thrombosis. There are claims to havedemonstrated a state of altered blood coagulabilityin patients with established ischaemic heart disease.In one series a ' heparin loading test 'has been saidto reveal a hypercoagulable state (Ulutin andSestakof, I958). McDonald and Edgill (1957)

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claimed an increase in blood coagulability in agroup of patients with ischaemic heart diseasecompared with healthy controls. This was basedon greater thromboplastin generation, faster pro-thrombin time (using Russell Viper Venom asthromboplastin), increased plasma fibrinogen andincreased platelet stickiness. We (Merskey,Gordon and Lackner, 1958, I959) found nodifference in the prothrombin time (using Russellviper venom as thromboplastin), but there was alittle greater thromboplastin generation in thecoronary group. We confirmed that patients overthe age of 50 with established ischaemic heartdisease have a higher plasma fibrinogen thansimilar age-matched controls. We did not esti-mate platelet stickiness. In any case, as McDonaldand Edgill are careful to point out, these effectsmay be a result of the disease rather than a cause.One of the great difficulties is that the so-calledage-matched 'control' group contains many in-dividuals with occult coronary artery disease. Inan attempt to overcome this difficulty we testedBantu subjects (in whom coronary artery diseaseis rare) and found these to have diminished pro-thrombin and factor 7 and in this respect theirblood might be considered less coagulable.Curiously there seemed to be an increase in theantihaemophilic factor in Bantu plasma as well asmore efficient prothrombin consumption, and inthis regard this blood was possibly more coagu-lable. Thromboplastin generation was equal tothat of the coronary group and more than thecontrols. We thus found very little to supportthe thesis that the relative immunity to coronaryartery disease of the Bantu was caused by anydiminution in the tendency of the blood to clot;one might even claim that their blood had agreater tendency to clot.

In summary, therefore, one can say that thoughthere have been many claims to have demonstratedincreased coagulability of the blood in thrombotic(or potentially thrombotic) states, there is nounanimity of opinion on the subject and the casecan by no means be considered as established. Theevidence against increased coagulability of theblood is no less convincing than the evidence inits favour. This subject has recently been re-viewed by Poole (1958).

Approaching the problem from a completelydifferent direction, one could consider the effectof mechanisms which inhibit coagulation or whichremove clots once they are forming or haveformed., Anticoagulant therapy is widely used inatheromatous conditions and many believe itexerts a beneficial effect. Despite some un-repentant sceptics like McMichael (1958) it isprobable that the patient who has an acutecoronary thrombosis has a better chance of coming

out of hospital alive if he has anticoagulant therapythan if he does not. One should, however, bewary of citing this as evidence that ' clotting'plays a part in this disease. A large number ofanticoagulant drugs have been claimed to beeffective; this is perhaps the best evidence wehave. It seems hardly likely that they all work bymeans of some other, as yet, unidentified action.Even so, do they necessarily save lives by prevent-ing coronary thrombosis? Honey and Truelove(I957), after a careful analysis, concluded that theoverall effect of anticoagulant therapy on thefatality rate of acute coronary thrombosis has notbeen very great and the improvement could beaccounted for by the almost complete abolition ofdeaths from pulmonary embolism.

If Duguid is right there would, perhaps, bejustification for long-term anticoagulant therapy.Here, too, there are very conflicting claims. Thereis very little evidence that anticoagulants can re-move pre-existing thrombi. Wright, Kubik andHayden (I953) and Wright (I954) showed thatoral anticoagulants (ethyl-biscoumacetate or phen-indione) could cause disappearance of artificiallyproduced thrombi in the femoral arteries of rab-bits, while Loewe and Hirsch (I947) showed thatheparin caused clots in jugular veins of rabbits todisappear. Nevertheless, many patients on long-term anticoagulant therapy have not been relievedof their angina (Gabrielsen and Myhre, 1958;Manchester, 1957). As regards saving of lifeafter long-term anticoagulant therapy, once againthe evidence is not very good and is also con-flicting. Suzman, Ruskin and Goldberg (I955)found these drugs to be life-saving especially whenthe presenting attack of infarction was severe andrecurrent. Wright et al. (1954) and Manchester(I957) also found anticoagulants to be helpfulwhen continued over a period of years., On theother hand, Bjerkelund (I957), in the best con-trolled study published to date, recorded benefitonly during the first year of treatment and only inpatients under the age of 60 years. One could,however, take issue with him when he comparesthe fate of survivors after the first year on anti-coagulant therapy with the survivors who did nothave such therapy, since the first group containsmany who could otherwise have died and must,therefore, be rated as 'worse risks' from thebeginning of the second year.

In summary we feel that anticoagulant drugshave probably made a difference to the prognosisof this disease in acute cases of coronary thrombosisas well as when these drugs are used continuouslyfor long-term treatment. It is probable that thebeneficial effect is mediated through an anti-coagulant mechanism, though the mechanism ofthis is not, at the moment, very clear.

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It is now generally accepted that there exists inthe blood a fibrinolytic enzyme which is capableof dissolving fibrin clots. The fibrinolytic activityof blood, as tested in vitro, is labile, and normallyof a low order of activity. The relationship be-tween fibrinolysis and coronary artery disease is atthe moment largely speculative. It seems not veryunreasonable to suppose that decreased fibrino-lytic activity might play a part in the pathogenesisof atheroma. Artificially-induced fibrinolysis, onthe other hand, may in the future prove to be ofvalue in the removal of intravascular thrombi.

If one accepts Duguid's concept that atheromais due to fibrin deposition in the lining of thearteries, it is only one step further to suggest thatfibrinolytic activity may be concerned in the dis-solution of these deposits, thus preventing theirincorporation within the vessel wall and the pro-duction of atherosclerosis. Greig (I956) hasshown that, following a fatty meal, the fibrinolyticactivity of the blood is considerably diminishedand suggested that this finding may be the con-necting link between Duguid's theory and thereports that a diet rich in animal fats plays an im-portant part in the production of atheroma.Moreover, Kwaan and McFadzean (1957) haveshown that rabbits fed on a diet rich in cholesteroltook four times as long to lyse artificially-producedvenous thrombi, than did the normal controls.Both these claims are as yet unconfirmed. Evenif they are true, we have very considerable reserva-tions regarding their importance in this problem.On comparing the fibrinolytic activity of the

blood in a group of normal Bantu males in Durbanwith Greig's (I956) report on White controls inJohannesburg it was found that the Bantu hadmore fibrinolytic activity than the White (Gillman,Naidoo and Hathorn, I957). In groups of Bantuand White males studied by ourselves, we(Merskey, Gordon and Lackner, 1958) found themean clot lysis time for the Bantu group to be5.6 hours and for the White control groups 10.4hours, the difference being statistically highlysignificant ,(P<o.ooi). We were unable todemonstrate any difference between the clot lysistime of normal White controls and of patients whohad undoubted ischaemic heart disease.

Since coronary artery disease is practically un-known in the Bantu, this finding could be held tosupport the concept that the lower fibrinolyticactivity in the blood in White men may play a partin the production of atheroma, but the absence ofa difference in our two White groups would re-quire to be explained. Hume (1958), on the otherhand, has shown that for io days following myo-cardial infarction there is marked depression andundue fluctuation of fibrinolysis. Whether thisphenomenon is the cause or the result of the in-

farction has not been established. The role thatfibrinolysis plays in the aetiology of atheroma andmyocardial infarction is, at present, largely specu-lative and we doubt whether it is of majorsignificance.

Artificially-induced fibrinolysis may prove to bean important advance in the treatment of intra-vascular thrombosis. This work, which is still inits infancy, is being tackled from two differentaspects. Meneghini (1958) stimulated the patients'own fibrinolytic system by injection of protein-free pyrogenic lipopolysaccharides. This is asso-ciated with considerable constitutional upset,which is incompletely controlled by administrationof salicylate. Results seem to be encouraging,especially in cases of venous thrombosis, but thismethod is not suitable in cases of coronary throm-bosis because of the unpleasant and severe side-effects. Cliffton, Grossi and Cannamela (1954)and Back, Ambrus, Goldstein and Harrison (I956),on the other hand, injected a previously preparedfibrinolysin (plasmin) in the form of streptokinase-streptodornase (SK-SD) activated plasminogen.Again results are better in cases of venous throm-bosis than in those of arterial thrombosis. Un-toward side reactions in the form of chills, fever,cyanosis and hypotension seem to be related toan excess of SK-SD and can be somewhatdiminished by using less activator. Since thereactions with this method are less severe, thereis hope that a non-toxic preparation might bedeveloped which could be used in the treatmentof coronary thrombosis.The part that blood lipids play in the problem

of ischaemic heart disease is reviewed elsewhere(Bronte-Stewart, I958). What part do they playin blood coagulation? Heparin, for instance, hasa ' fat-clearing action' as well as an anticoagulantaction. It was hoped that a study of the Bantumight reveal differences in blood coagulation,since the Bantu have both less serum cholesteroland less coronary artery disease. The somewhatconfusing results have already been discussed. Inrabbits, if the plasma cholesterol is raised to ex-cessive levels, there is a diminished tendency ofthe blood to clot while at the same time cholestero-losis of the aorta develops (Merskey, 1957). Ratsfed large amounts of cholesterol and fat andthiouracil form thrombi in the coronary vesselsand develop myocardial infarction (Hartroft andThomas, 1957). None of these observations ap-pears to have any direct bearing on human disease.There is a little evidence on the effect of an acute

fat load on blood coagulation which is worth men-tioning. It is not difficult to show that fat addedto blood in a test tube materially accelerates bloodcoagulation (Poole, 1955, 1958). This is not thesame thing as saying that fat taken by mouth can

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have this effect. Waldron and co-workers (1951,1954) claimed that ingested fats accelerated co-agulation of blood, and similar claims were putforward by Fullerton, Davie and Anastasopoulos(I953), O'Brien (1955), Keys, Buzina, Grande andAnderson (i957), and by others. The coagulationtime of the blood in silicone tubes was said to beshortened and so was the co-called ' Stypven'time (one-stage plasma thromboplastin time using,Russell Viper Venom as thromboplastin). Noeffect of ingested fat on coagulation time of bloodin silicone tubes could be shown by Tulloch,Overman and Wright (1953), by Manning andWalford (1954), by Sheehy and Eichelberger(I958), by Borrero, Sheppard and Wright (1958),by Merskey and Nossel (957), or by Sohar,Rosenthal and Adlersberg (957). These last twogroups of workers also used a large number ofother tests of coagulation efficiency without ob-taining convincing evidence of the effect of post-prandial hyperlipaemia on blood coagulation.Curiously enough, even O'Brien (I955), whoclaimed that fat shortened the coagulation time,could not demonstrate any correlation betweenthis shortening and the changes in the total etherextractable fatty acids in the plasma or the opacityof the plasma. Nor could he demonstrate adifference in the reaction of coagulation time to anacute fat load in normal subjects and those withcoronary artery disease (O'Brien, 1958). Allworkers agreed that fat taken by mouth shortenedthe Stypven time, especially in platelet-poorplasma (or in platelet-containing plasma if theplatelets had not been allowed to rupture andrelease their contained phospholipid). Muchenergy was expended in identifying the fat whichwas responsible for the effect and there were manyconflicting results. In 1936 Trevan and Mcfarlaneshowed that the addition of crude lecithin to re-calcified citrate plasma with Russell Viper Venomaccelerated clotting. Ethanolamine phosphatidehas the same action as crude lecithin and it seemsto have the same effect on enhancing thrombinformation whether it is prepared synthetically orwhether it is derived from brain or egg yolk(Poole and Robinson, 1956). O'Brien (I957), whohas reviewed this subject extensively, feels that itis likely that the post-prandial acceleration of theStypven time could be due to the presence in theplasma of any one of a number of identified, or asyet unidentified, phospholipids. But many wouldquery the validity of conclusions based on such anartificial test as the Stypven time. It is sensitiveto the presence of fat, but there is hardly anyevidence that it plays a part in vivo. Finally,while fats of different degrees of saturation or un-saturation have varying effects on the serum-cholesterol level the degree of saturation seems to

play little part in this Stypven time (Merskey andNossel, I957; O'Brien, 1957), since both saturatedand unsaturated fats may shorten the Stypventime.

This brief and admittedly very incomplete re-view shows how little concrete evidence there isthat alterations in the coagulability of the bloodplay a part in the pathogenesis of coronaryatheroma and in the production of ischaemic heartdisease. It remains an attractive theory, but theevidence in favour of it is scanty. The techniquesof assaying coagulation which we have at ourdisposal are crude and sensitive to a host of ex-traneous factors. They must be done withmeticulous care, be adequately (and even, perhaps,excessively) controlled, and even then looked atwith a somewhat sceptical eye. Possibly one daywe may have other techniques available, moresensitive, more reproducible and, perhaps, evenmore meaningful. Until that time we would bewell advised to conclude that while fat, atheromaand blood coagulation may be linked in some way,available evidence is insufficient for us at themoment to draw any definite conclusions.

BIBLIOGRAPHYALEXANDER, B. (1955), New Engl. J. Med., 252, 526.BACK, N., AMBRUS, J. L., GOLDSTEIN, S., and HARRISON,

J. W. E. (1956), Circulation Research, 4, 440.BARKER, N. W., and MARGULIES, H. (I949), 'Blood Clotting

and Allied Problems,' Transactions 2nd Conference JosiahMacy, Jnr., Foundation, p. 106.

BEAUMONT, J. L., CHEVALIER, H., and LENEGRE, J. (1953),Amer. Heart J., 45, 756.

BIGGS, R., and MACFARLANE, R. G. (1957), 'Human BloodCoagulation and Its Disorders,' Blackwells, Oxford.

BJERKELUND, C. J. (1957), Acta. med. scand., 158, suppl. 330.BORRERO, J., SHEPPARD, E., and WRIGHT, I. S. (I958),

Circulation, 17, 936.BOYD, W. (1953), 'A Textbook of Pathology,' 6th ed., p. 324,

Henry Kimpton, London.BRANWOOD, A. W., and MONTGOMERY, G. L. (1956),

Scottish M. J., i, 367.BRONTE-STEWART, B. (1958), this Journal, p. ooo.CLIFFTON, E. E., GROSSI, C. E., and CANNAMELA, D.

(1954), Ann. Surg., 139, 52.CUMMINE, H., and LYONS, R. N. (1948), Brit. J. Surg., 35, 337.DUGUID, J. B. (1926), J. Path. Bact., 29, 37I.DUGUID, J. B. (1946), Ibid., 58, 207.DUGUID, J. B., and ROBERTSON, W. B. (I957), Lancet i, 1205.EISEN, M. E., TYSON, M. C., MICHAEL, S., and BAUMANN,F. (I951), Circulation, 3, 271.FULLERTON, H. W., DAVIE, W. J. A., and ANASTASO-

POULOS, G. (1953), Brit. med. J., ii, 250.GABRIELSEN, Z., and MYHRE, J. R. (1958), Circulation, 17, 348.GILLMAN, T., NAIDOO, S. S., and HATHORN,'M. (I957),Lancet, ii, 696.GREIG, H. B. W. (1956), Ibid., ii, i6.HAGEDORN, A. B., and BARKER, N. W. (I948), Amer. Hearty.,

35, 603.HARTROFT, W. S., and THOMAS, W. A. (1957), J. Amer. med.

Ass., 164, 1899.HONEY, G. E., and TRUELOVE, S. C. (1957), Lancet, i, II55.HOOFF, A. VAN DEN (1955), Ibid., ii, 1392.HOOFF, A. VAN DEN (1956), Ibid., i, 247.HUME, R. (I958), Brit. Heart J., 2o, I5.HURN, M., BARKER, N. W., and MANN, F. D. (I947), Amer.

J. din. Path., 17, 709.INGRAM, G. I. C., BIGGS, R., and ARMITAGE, P. (1953),J. clin. Path., 6, 46.KEECH, M. K., and REED, R. (I955), Lancet, ii, 1392.Bibliography continued on page 222

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virtually no change in the prevalence of the diseasemeasured electrocardiographically in the threeracial groups during the period under review(1952 to 1957).The effect of sex on the prevalence of infarction

was again well borne out during 1957 in all races.Only 64 of the 262 cases in Whites were women,and 56 of these were 50 or over, with a peakprevalence between 60 and 69. In the 79 Colouredcases, 22 were women, I7 were 50 and over, witha similar peak prevalence between 60 and 70. Nocase of ischaemic heart disease has yet been en-countered in a Bantu female. The peak incidencein White and Coloured males was between 50 and59, with 27 per cent. of the Whites below 50 and37 per cent. of the Coloureds. The only Bantucase was over 70 years old. These figures are verysimilar to those published for 1952 to 1956(Schrire, I958a).Conclusions

Electrocardiograms of 3,525 adults attending theGroote Schuur Hospital and the New SomersetHospital, Cape Town, during I957 were analysedto determine the inter-racial prevalence of myo-cardial infarction.

Electrocardiographic evidence of myocardial in-

farction was found in only one Bantu during 1957and this patient had been seen before in previousyears.

Electrocardiographic evidence of myocardial in-farction and ischaemic heart disease was found farmore commonly in the White than in the CapeColoured, in both of whom the disease wascommon.The higher prevalence of ischaemic heart disease

in Whites than in non-Whites was confirmed andwas not attributable to a significant difference inage distribution of the population studied.The peak prevalence in males was between 50

and 59 and in females between 60 and 69. Thedisproportionate prevalence in males was con-firmed.The results were compared with the findings of

previous years.BIBLIOGRAPHY

CONYBEARE, J. (1952), Guy's Hosp. Gaz., 66, 421.OSLER, W. (I910), Lancet, i, 697.PATON, B. C. (1957), Amer. J. Med., 23, 76r.RYLE, J. A., and RUSSELL, W. T. (1949), Brit. Heart J., I, 370.SCHRIRE, V. (I958a), Amer. Heart J., 56, 280.SCHRIRE, V. (I958b), S. Afr. med. J., 32, I77.STOCKS, P. (I951), Lancet, i, 35I.THOMAS, A. J., COCHRANE, A. L., and HIGGINS, I. T. T.

(1958), Ibid., ii, 540.VOGELPOEL, L., and SCHRIRE, V. (i955), Ibid., ii, 10o8.

Bibliography continued from page 207-C. Merskey, .(Cape), .C.P.(LCondon), and H. Lackner, M.D.(Leeds)M.R.C.P.(London)

KEYS, A., BUZINA, R., GRANDE, F., and ANDERSON, J. T.(1957), Circulation, 15, 274.

KOLLER, F. (1954), in 'Thrombosis and Embolism,' p. II2,B. Schwabe and Co., Basel.

KWANN, H. C., and McFADZEAN, A. J. S. ('957), Nature, 179,260.

LEVENE, C. I. (1955), Lancet, ii, 1216.LEVENE, C. I. (1956), Ibid., i, Io5.LEVINE, S. A., and BROWN, C. L. (1929), Medicine, 8, 245.LOEWE, L., and HIRSCH, E. (I947),J. Amer. med. Ass., 133, 1263.MANCHESTER, B. (1957), Arch. intern. Med., 100, 959.MANNING, P. R., and WALFORD, R. L. (1954), Amer. J. med.

Sci., 228, 652.McDONALD, L., and EDGILL, M. (I957), Lancet, ii, 457.McMICHAEL, J. (1958), Ibid., i, 528.MENEGHINI, P. (1958), Acta Haemat. (Basel), 19, 65.MERSKEY, C. (x957), Brit. J. Haematol., 3, 366.MERSKEY, C., GORDON, H., and LACKNER, H. (1958),

S. Afr. med. J., 32, 855.MERSKEY, C., GORDON, H., and LACKNER, H. (I959), to

be published.MERSKEY, C., and NOSSEL, H. L. (1957), Lancet, i, 806.MOOLTEN, S. E., VROMAN, L., and VROMAN, G. M. S.

(I949a), Amer. J. din. Path., 19, 814.MOOLTEN, S. E., VROMAN, L., VROMAN, G. M. S., and

GOODMAN, B. (1949b), Arch. intern. Med., 84, 667.MORGAN, A. D. (1956), 'The Pathogenesis of Coronary Occlu-

sion,' Blackwells, Oxford.MUIR, R. (I95s), in 'Muir's Textbook of Pathology,' 6th ed.,

p. 293, Edward Arnold, London.de NICOLA, P. (1953), ' Texas Report on Biology and Medicine,'

II, 3.O'BRIEN, J. R. (I955), Lancet, ii, 690.O'BRIEN, J. R. (I957), Amer. J. med. Sci., 234, 373.O'BRIEN, J. R. (1958), Lancet, i, 410.PATERSON, J. C. (X938), Arch. Path., 25, 474.

'A'i'ERSON, 1. C., and :McLACHLIN, J. (1954), Surg Gynec.Obstet., 98, 96.

PEEL, A. A. FITZGERALD (1956), Brit. Heart ., I8, 378.POOLE, J. C. F. (I955), Brit. J. exp. Path., 36, 248.POOLE, J. C. F., and ROBINSON, D. S. (I956), Quart. J. exp.

Physiol., 4I, 295.POOLE, J. C. F. (1958), Brit. med. Bull., I4, 253.RODBARD, S. (1956), Circulation, 14, 483ROKITANSKY, C. (841), ' Manual of Pathological Anatomy,'

cited by Morgan (1956).SHEEHY, T. W., and EICHELBERGER, J. W., Jnr. (1958),

Circulation, 17, 927.SOHAR, E., ROSENTHAL, M. C., and ADLERSBERG, D.

(I957), Amer. J. din. Path., 27, 503.SUZMAN, M. M., RUSKIN, H. D., and GOLDBERG, B. (1955),

Circulation, 12, 338.de TAKATS, G. (I943), Surg. Gynec. Obstet., 77, 31.TREVAN, J. W., and MACFARLANE, R. G. (1936), Report of

the Medical Research Council for the year 1936-37, p. 143.TULLOCH, J. A., OVERMAN, R. S., and WRIGHT, I. S. (1953),

Amer. J. Med., 14, 674.ULUTIN, O. N., and SESTAKOF, D. (1958), Lancet, i, 324.WALDRON, J. M., BEIDELMAN, B., and DUNCAN, G. G.

(I95I), Gastroenterology, 17, 360.WALDRON, J. M., and DUNCAN, G. G. (I954), Amer. J. Med.,

I7, 365.WARREN, R. (I953), New Engl. J. Med., 249, 99.WRIGHT, H. P. (I942), J. Path. Bact., 54, 461.WRIGHT, H. P., KUBIK, M. M., and HAYDEN, M. (1953),

Brit. med. J., i, I02I.WRIGHT, H. P. (1954), in ' Thrombosis and Embolism,' p. 565,

B. Schwabe and Co., Basel.WRIGHT, I. S., BOURGAIN, R. H., FOLEY, W. T., Mc-

DEVITT, E., GROSS, C., BURKE, G., SIMON, E.,LIEBERMAN, J., SYMONS, C., and HUEBNER, R. (1954),Circulation, 9, 748.

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