Br HeartJ_ 1994;71:316-321

Serum Lp(a) lipoprotein concentration andoutcome of thrombolytic treatment formyocardial infarction

Anthony D MBewu, Paul N Durrington, Michael I Mackness, Linda Hunt,Wajdi H Turkie, John E Creamer

AbstractBackground-Lp(a) lipoprotein hasstructural homology with plasminogenand has been shown to inhibit plasmino-gen activation in vitro.Objective-To determine whether theserum concentration of Lp(a) lipoproteinpresent when streptokinase was given inacute myocardial infarction influencedthe outcome as judged by electrocardio-graphic methods.Patients and design-Serum Lp(a)lipoprotein concentration was measuredin 135 consecutive patients admitted witha diagnosis of acute myocardial infarc-tion who received streptokinase treat-ment. Recovery from myocardial injurywas assessed by the reduction in the sumof ST segment elevation measured fromthe J point (SiJ) in the electrocardio-gram immediately before streptokinasewas given compared with that threehours later.Results-The serum Lp(a) lipoproteinconcentrations were measured within 12hours of the onset of symptoms ofmyocardial infarction and were higherthan in healthy reference populations.Recovery from myocardial infarctioncould be assessed from the STJ in 116patients (86% of the series). Those inwhom it could not had bundle branchblock, left ventricular hypertrophy, didnot survive three hours, or had startedintravenous nitrate treatment or someother clinical procedure before or at thetime the second electrocardiogram was tobe recorded. Patients with reductions inSTJ after streptokinase that were > 4mm (the median decrease) had mean(range) serum Lp(a) lipoprotein concen-trations of 410 (0.8-220) mg/dl and thosewith a smaller reduction in STJ had con-centrations of 29-1 (1-7-151) mgldl. Thedifference was not statistically signifi-cant.Conclusion-In this study Lp(a) lipopro-tein concentration did not significantlyinfluence the outcome of thrombolytictreatment with streptokinase.

(Br HeartrJ 1994;71:316-321)

Thrombolysis is well established in the treat-ment of myocardial infarction1-3 and has beenshown to increase patency of the infarctrelated coronary artery,4 reduce the size of the

myocardial infarct,5 preserve left ventriculardimensions and function,67 and reduce bothearly and late mortality.89The Lp(a) lipoprotein is widely held to be

an important risk factor in coronary heart dis-ease. High serum Lp(a) lipoprotein concen-trations are associated with an increasedprevalence of angina pectoris, myocardialinfarction, and coronary artery diseaseassessed angiographically.1S-2 The Lp(a)lipoprotein has close structural homology withplasminogen13 and can impede fibrinolysis atthe surface of cultured human endothelialcells.14 Enormous doses of thrombolytic agentare used in the treatment of myocardialinfarction, however, which might be predictedfrom in vitro studies, to overwhelm any com-petition by Lp(a) lipoprotein."5 None the lessin vivo similar kinetic considerations may notapply locally at a thrombosis in a coronaryartery and the possibility remains that Lp(a)lipoprotein might impede plasminogen activa-tion or compete with plasminogen and plas-min treatment impeding breakdown of thefibrin clot.We therefore investigated the influence of

the prevailing serum concentration of Lp(a)lipoprotein on the clinical outcome of acutemyocardial infarction treated with streptoki-nase.

Patients and methodsPATIENTSApproval for this study was obtained from theClinical Ethics Committee of our hospital,and all patients participating gave theirinformed consent. All patients admitted to thecoronary care unit with a diagnosis of acutemyocardial infarction were treated with strep-tokinase unless there were specific contraindi-cations-namely, more than 12 hours sincethe onset of continuous chest pain; confirmedpeptic ulcer within the previous six months;current symptoms suggestive of peptic ulcer;cerebrovascular accident within the past 12months; bleeding diathesis; recent surgery(less than three months); streptokinase treat-ment within the past six months.

Between September 1989 and February1991 162 consecutive patients were admittedto our coronary care unit with a diagnosis ofdefinite myocardial infarction and no contra-indication to streptokinase. Two died imme-diately leaving 160 who were treated withintravenous streptokinase (1 *5 MU overone hour, Hoechst Streptase or KabiVitrum Kabikinase). Venous blood was taken

University ofManchesterDepartnent ofCardiologyA D MBewuW H TurkieJ E CreamerUniversity ofManchesterDepartnent ofMedicineP N DurringtonM I MacknessUniversity ofManchester Faculty ofMedicineComputationalGroup, ManchesterRoyal InfirmaryLinda HuntCorrespondence to:Dr Paul N Durrington,The University Departmentof Medicine, ManchesterRoyal Infirmary, OxfordRoad, Manchester Ml 39WL.Accepted for publication1 November 1993.

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immediately before the infusion of strepto-kinase for the determination of serum Lp(a)lipoprotein and plasma fibrinogen. SerumLp(a) lipoprotein values before streptokinasewere obtained for 135 patients (eight declinedto participate, and in 17 cases no satisfactorysample was obtained for measurement gener-ally because the clinical team on duty startedthe streptokinase infusion before obtainingblood for the study or because of clinicalurgency). In a subset of patients serum Lp(a)lipoprotein and fibrinogen were also mea-sured at the end of the streptokinase infusion.We include the fibrinogen results. There wasno change in serum Lp(a) lipoprotein concen-trations after the infusion of streptokinase.'6

Twelve weeks after the myocardial infarc-tion, patients were seen in our clinic by ADMto check for recurrent angina, heart failure,changes in medication, blood pressure,weight, and height. On this occasion a fastingblood sample was obtained after the patienthad fasted since 22 00 the previous night. Theserum cholesterol, triglyceride, high densitylipoprotein cholesterol, and apolipoprotein Bresults presented here were obtained from thissample. In a subset of patients it was shownthat these values were not significantly differentfrom those obtained on admlssion.'6Seventeen (12-6%) of the 135 patients withLp(a) lipoprotein values before streptokinasehad died by the time of the 12 week visit.Data for some variables are incomplete forthis reason.

CARDIOLOGICAL INVESTIGATIONThe diagnosis of myocardial infarction wasbased on a history of typical, prolonged (>30minutes) chest pain, plus diagnostic electro-cardiographic changes of >2 mm of ST seg-ment elevation in at least two contiguousprecordial leads on the admission electrocar-diogram or > 1 mm of ST elevation in two ormore inferior electrocardiographic leads, plusa diagnostic rise in serum cardiac enzymes.The electrocardiogram on admission to

hospital was taken by trained nurses in thecasualty department or coronary care unit andvenous blood was taken at that time forestimation of serum Lp(a) lipoprotein.Streptokinase was given as soon as possibleonce the diagnosis was made and the patientwas given aspirin (150 mg) to chew (providedthere was no history of allergy to aspirin). Nopatients had an allergy to aspirin but 10 of the153 (6 5%) patients did not receive aspirinbecause of a history of peptic ulcer or dys-pepsia.A second electrocardiogram was performed

three hours after starting streptokinase. Thiswas compared with the electrocardiogramrecorded immediately before the streptoki-nase. Changes in the sum of ST elevation inall 12 leads of the electrocardiogram at the Jpoint (STJ) and 60 ms after the J point weremeasured. Changes in the degree of ST eleva-tion in the lead with the maximum ST eleva-tion (STmax) at the start of streptokinaseinfusion were also measured. The decline inthe sum of ST elevation in the electrocardio-

gram has previously been shown to correlatewell with recovery from myocardial injury andreperfusion of the infarct-related artery.'7-19 Ofthe 135 patients studied 116 had electrocar-diograms that could be analysed. Six couldnot because of left or right bundle branchblock or left ventricular hypertrophy, fourcould not because the patients died before thesecond electrocardiogram, and nine wereexcluded because intravenous nitrate infusionhad been given to the patients in the intervalbetween the first and second electrocardio-gram or the second electrocardiogram couldnot be recorded at three hours because thepatient's condition demanded some othermore urgent clinical procedure at the time.

Electrocardiograms were performed dailyduring the 48 hour or longer stay on the coro-nary care unit and again before dischargefrom hospital, and the clinical progress of thepatient was monitored by one of us. The elec-trocardiogram recorded before discharge fromhospital was used to calculate a Selvesterscore, which correlates well with the size ofthe myocardial infarction.202'

Sixty five of the patients had coronaryangiography at a median of six days afterthrombolysis, and these films were used tocheck for patency of the infarct related arterywith a protocol from the Thrombolysis inMyocardial Infarction Study.4 Coronaryangiography was performed in all patientsunder the age of 50 for men and 65 forwomen (n = 24) and in patients with recur-rent chest pain after myocardial infarction(n = 39), or for other clinical indications(n = 2), unless there were contraindicationssuch as massive myocardial infarction withpoor ensuing left ventricular function.The films were independently scrutinised

by two experienced angiographers on differentoccasions to assess the patency of the infarctrelated artery.4 Both observers were unawareof the clinical state or blood results of thepatients.

LABORATORY METHODSHigh density lipoprotein cholesterol wasmeasured by the managanese/heparin precipi-tation method.22 Serum total cholesterolwas determined enzymatically (reagentsupplied by Diamed, Murten, Switzerland)and serum triglycerides by the glycerylphosphate oxidase-peroxidase-aminophenazonemethod (Boehringer Mannheim, Mannheim,Germany). Within batch coefficients of varia-tion for cholesterol and triglyceride assayswere 1 5% and 2 1% respectively. Our labora-tory participates in the national qualitycontrol scheme. Apolipoprotein B was deter-mined by immunonephelometry with theBeckman Array (Beckman Instruments, PaloAlto, California, USA). The antiserum toapolipoprotein B was supplied by Beckman.The method was repeatedly calibrated againsta secondary serum standard, the apolipopro-tein B concentration of which was determinedby immunoelectrophoresis with a primarystandard of lipoprotein of density 1 040-1 053 g/ml isolated by ultracentrifugation.22

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Table 1 Characteristics ofpatients on admission to the coronary care unit (mean (SD))or median (range))

Patients whose ST Patients withchange could be coronary

Al patients measured angiograms

No (M:F) 135(106:29) 116(91:25) 62(53:9)Age (y) 58(32-82) 59(32-82) 54(34-71)Serum cholesterol (mmol/l) 6-81(1-52) 6-74(1-54) 6-84(1-52)Serum triglycerides (mmoIl/) 2-23(0-61-8-64) 2-22(0-61-8-64) 2-25(0-90-8-17)Serum HDL cholesterol (mmol/l) 0 9(0 35) 0-91(0-35) 0-91(0-40)Serum apolipoprotein B (mg/dl) 113(31) 111(31) 113(32)Serum Lp(a) lipoprotein (mg/dl) 34 0(0 8-220 0) 34 7(0 8-220 0) 24-2(0-8-184-8)Plasmafibrinogen (g/l) 3-26(1-11) 3-26(1-12) 3-29(0 94)Smokers (%) 60 58 64Previous MI(%) 18 18 18Systolic BP (mm Hg) 140(33) 141(34) 136(26)Diastolic BP (mm Hg) 86(21) 86(21) 87(16)Quetelet's index (Kg/M2 26-1(3-9) 25 9(3-8) 26 9(3 9)

Complete data were available for Lp(a) lipoprotein and for > 85% of patients for other variablesexcept HDL (76%), apolipoprotein B (73%), fibrinogen (53%), and Quelelet's index (80%).HDL, high density lipoprotein, MI, myocardial infarction.

The Lp(a) lipoprotein was determined by atwo site immunoradiometric assay(Pharmacia, Uppsala, Sweden) previouslyevaluated in this laboratory.'0 This methodshows no cross immunoreactivity with plas-minogen or with low density lipoprotein, andhas a lower detection limit of 0-06 mg/dl. Themethod was calibrated in our laboratoryagainst the standard provided by Pharmacia.The results were expressed as mg total proteinin Lp(a) lipoprotein (apolipoprotein(a) andapolipoprotein B) per dl serum, after repeatedcomparisons of the results obtained with thestandard and preparations of Lp(a) lipopro-tein isolated from pooled serum by ultracen-trifugation and affinity chromatography. Theprotein concentration of these was deter-mined by a modification of the Lowrymethod. The within batch coefficients of vari-ation for the apolipoprotein B and Lp(a)lipoprotein assays were 5-4% and 2a1%respectively. In all lipid and apolipoproteinassays quality control serum samples wereincluded to ensure that between batch varia-tion was within acceptable limits. Serum crea-tine kinase activity was measured in theroutine clinical chemistry laboratory for threedays after admission.

STATISTICSThe unpaired Student's t test was used tocompare the means of the variables, whichwere normally distributed. Serum Lp(a)lipoprotein concentrations and coronary

Table 2 Serum Lp(a) lipoprotein concentrations (median (range)) in patients above andbelow median change in ST segment elevation over the three hours after the intravenousinfusion ofstreptokinase

Change in ST segment Serum Lp(a) lipoproteinelevation No (mgldl) p value*

J point:<4mm 56 29-1 (1-7-151)

0-087> 4mm 60 41-0 (0-8-220)

60 ms:< 4mm 57 28-8 (1-7-215)

0-089, 4 mm 59 39-9 (0 8-220)

ST max:<1-5mm 48 26-8 (1-7-151)

0-083> 1-5 mm 68 41-0 (0-8-220)

*Mann-Whitney test (two tailed)

artery disease (Selvester) scores were com-pared with the non-parametric Mann-Whitney U test. Qualitative variables with twocategories (sex, number with previousmyocardial infarction, family history of coro-nary heart disease, smokers, proportion ofpatients with occluded infarct related arterywho have serum Lp(a) lipoprotein > 25mg/dl, percentage of patients with serumLp(a) lipoprotein greater or less than themedian Lp(a) lipoprotein, and percentage ofpatients with STJ greater or less than themedian STJ) were compared with the 2 x 2 %2test or Fisher's exact test (if the numbers weresmall).

Correlations between variables were soughtwith Kendall's test. The Wilcoxon matchedpairs test was used to compare Lp(a) lipopro-tein before myocardial infarction and at 12weeks after myocardial infarction. Two tailedtests are reported throughout.

ResultsPATIENTS STUDIEDTable 1 shows the clinical characteristics ofthe patients. The patients tended to have highcholesterol and triglycerides and low highdensity lipoprotein cholesterol compared withtypical values for a healthy British population.The serum Lp(a) lipoprotein values werehigh, the median value in healthy local peoplebeing 10 mg/dl." The site of the myocardialinfarction on electrocardiographic criteria wasinferior in 48%, anterior in 45%, posterior in4%, and lateral in 3%. The median (range)time between the onset of chest pain and thestart of the intravenous infusion of streptoki-nase was three (0-5-14) hours.

MORTALITYSeventeen (12-6%) ofthe 135 patients investi-gated died during the next three months. Themedian (range) serum Lp(a) lipoprotein con-centration immediately before streptokinasein those who died was 28-8 (1-7-85-0) mg/dl,which was not significantly different fromthose who survived (34 0 (0 8-220-0) mg/dl).There was no significant relation betweenserum Lp(a) lipoprotein concentrations andmortality within the first three months orheart failure treated within the first three days.

ELECTROCARDIOGRAPHIC INDICES OFOUTCOME OF THROMBOLYTIC TREATMENTWhen patients whose ST segment recoveryexceeded the median rate were, comparedwith those with rates below this value (table 2)there was a tendency for serum Lp(a) lipopro-tein concentrations to be higher in patientswhose ST segments returned rapidly towardsthe isoelectric line than in those in whom itwas slower to return. This was so regardless ofthe measure of ST segment elevation used.The difference was not significant by twotailed tests, which we considered should beused because our original hypothesis was thathigh circulating Lp(a) lipoprotein at the timeof streptokinase infusion might unfavourablyaffect its outcome.

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Table 3 Characteristics of the 62 patients who had coronary angiography mean (SD))or median (range))

Infarct related arteuy

Occluded Patent

No (M:F) 17 (14:3) 45(39:6)Age (y) 58(36-71) 52(34-70)Previous myocardial infarction (%) 35 12*Smokers (%) 65 64Peak serumCreatine kinase (U/i) 1721(100-3954) 1430(239-6248)Time interval between streptokinase and

coronary angiogram (days) 6-0 (1-20) 6-0 (0-23)Time interval between onset of symptoms and

streptokinase (h) 3(1 25-11 00) 3(0 75-12 00)Serum cholesterol (mmolA) 6 68(1 99) 6.90(1.34)Serum apolipoprotein B (mg/dl) 110(31) 114(33)Serum triglyceride (mmol/1) 1-75 (0 9-4 94) 2-42(0-99-8-17)Serum HDL cholesterol (mmol/1) 0.88(0.40) 0 93(0 40)Serum Lp(a) lipoprotein (mg/dl) 28-8(44-96 6) 23-5(08-185)

*p = 0-085. All differences are NS. Data are incomplete for cholesterol, triglycerides, high densitylipoproteins, and apolipoprotein B, because some patients did not survive until 12 weeks (seemethods).

There was no significant correlationbetween the serum Lp(a) lipoprotein concen-tration and size of the myocardial infarctionassessed by electrocardiography.

CORONARY ANGIOGRAPHIC OUTCOME OFTHROMBOLYTIC TREATMENTThe 62 patients selected to have coronaryangiography were younger than the rest. Theywere also minimally more obese (p < 0 05)but in most other respects their clinical char-acteristics were similar to the others. Therewere also no significant differences in serumLp(a) lipoprotein concentrations or in otherlipid or lipoprotein variables between patientswith occluded and patent infarct related coro-nary arteries (table 3). There was a trend forhigher coronary artery disease scores and atendency for previous myocardial infarction inpatients with occluded infarct related coro-nary arteries.

HAEMATOLOGICAL RESPONSE TOTHROMBOLYTIC TREATMENTBefore the streptokinase infusion the mean(SD) plasma fibrinogen was 3-26(1l11) g/l(n = 71) and three hours afterwards it was0 67(0 45) g/l (n = 77). The pretreatmentplasma fibrinogen in patients with occludedinfarct related coronary arteries (3-53(1 15)g/l; n = 9) and the fibrinogen response tostreptokinase (079(077) gil; n = 10) werenot significantly different from those withpatent arteries (3-19(084) gil; n = 21 and0 74(0 56) g/l; n = 25). Furthermore plasmafibrinogen concentration did not differbetween patients with a > 4 mm fall in STsegment elevation and those in whom it was< 4 mm. There was no significant correlationbetween the change in plasma fibrinogen fromzero to three hours after the start of streptoki-nase treatment and the serum Lp(a) lipopro-tein concentration before streptokinaseinfusion (Kendall's tau = 0-106, NS).

CHANGE IN SERUM LP(A) LIPOPROTEINCONCENTRATION AFITER MYOCARDIALINFARCTIONPaired serum samples taken before streptoki-nase infusion and 12 weeks after myocardial

infarction were available for 84 patients.Median serum Lp(a) lipoprotein 12 weeksafter myocardial infarction was 42A4(08-2 10) mg/dl and before streptokinase was30-2 (0 8-220) mgidl. These values were ofborderline significance (p = 0'053).

DiscussionThere is an enormous volume of case-controlevidence linking serum Lp(a) lipoproteinconcentrations and premature coronary heartdisease.'10-2 Furthermore in European popula-tions a parental history of coronary heart dis-ease early in life is associated with increasedserum Lp(a) lipoprotein concentrations in off-spring. 1024 Also in familial hypercholestero-laemia, in which risk of coronary heart diseaseis greatly increased, the serum Lp(a) lipopro-tein concentration is raised.2325 Prospectivestudies are, however, less persuasive withone26 supporting Lp(a) lipoprotein as a deter-minant of risk of coronary heart disease andtwo failing to do SO.2728 In our investigationthe median Lp(a) lipoprotein value within 12hours of the onset of symptoms of acutemyocardial infarction was more than threetimes that of a healthy British population.23 It islikely that the Lp(a) lipoprotein value thisearly in the course of myocardial infarctionreflected its premorbid concentration and ourstudy thus supports the view that Lp(a)lipoprotein is predictive of myocardial infarc-tion. There was a tendency for serum Lp(a)lipoprotein concentrations to be higher 12weeks after myocardial infarction than imme-diately after it. Maeda and colleagues foundno acute changes in serum Lp(a) lipoproteinconcentrations in the week after myocardialinfarction, but there was a rise in somepatients during the second week.29 In a studyof similar design we confirmed the relativestability of serum Lp(a) lipoprotein in theweek after myocardial infarction with greatervariation in the concentrations in the secondweek.16 It is thus possible that the increase at12 weeks after myocardial infarction mayreflect this late rise in some people.The Lp(a) lipoprotein is distinguished from

other lipoproteins by possessing anapolipoprotein, apolipoprotein(a), which is amutation of plasminogen. It has a proteasedomain structurally similar to that of plas-minogen, but is not activated to lyse fibrin byplasminogen activators. Furthermore in placeof the short series of five kringles present inplasminogen, Lp(a) lipoprotein has a longseries of kringles due to repetition of kringleshomologous to the fourth kringle of plasmino-gen. The number of these repeats is deter-mined by a single genetic locus and isresponsible both for the genetic variation inthe molecular mass of apolipoprotein(a) andlargely for its circulating concentration.0

Because of its resemblance to plasminogenand its lack of activation by known plasmino-gen activating factors, Lp(a) lipoproteinseems an obvious candidate to inhibit fibrinol-ysis competitively. There are in vitro studiesthat show that it will bind to plasminogen

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receptors3" and to fibrin32 and that it willinhibit plasminogen activation.'4 One attemptto show that Lp(a) lipoprotein does bind toplasminogen receptors in vivo, however,proved negative." There have been three pre-vious studies in which in vivo evidence of aneffect of Lp(a) lipoprotein on thrombolysishas been sought with the clinical outcome ofpatients undergoing thrombolytic treatmentfor acute myocardial infarction as themodel.'4'6 In none of these reports was strep-tokinase used. Nor was the electrocardio-graphic response investigated. These studieswere small, involving only 20-50 patients, andbecause coronary angiography could not beundertaken without a clinical indication (as inour present study) they may have been con-founded by selection bias. The results of thesestudies, like ours, showed no effect of Lp(a)lipoprotein on the patency of infarct-relatedcoronary arteries.We considered that the electrocardio-

graphic response to thrombolytic treatmentmight provide an insight into the in vivo effectof Lp(a) lipoprotein in a larger, less biasedseries of patients than was possible with coro-nary angiography. This proved to be the casebecause it was possible to assess the rate ofrecovery of the ST segment elevation in 86%of a series of 135 patients. (The remaindercould not be assessed as their electrocardio-grams were unsuitable and showed abnormal-ities such as left bundle branch block and leftventricular hypertrophy). One factor limitingthe return of the ST segment to the isoelectricline when thrombolytic treatment has beengiven is whether the ischaemic myocardium issuccessfully reperfused.'9 We therefore rea-soned that were Lp(a) lipoprotein to interferewith thrombolysis a greater proportion ofpatients with high concentrations of serumLp(a) lipoprotein at the time they receivedstreptokinase would show a slower recovery inST segment elevation. We found no evidencefor this possibility in our study. Indeed, thepatients with the more rapid decline of STsegments had a median concentration ofLp(a) lipoprotein that was one third greaterthan that of those with a slower response.This trend was close to significance andwould have been so had our original hypothe-sis been that Lp(a) lipoprotein may have con-ferred some benefit. It is thus important toconsider alternative hypotheses that mightexplain the results. One suggestion is that thecoronary thrombosis, which forms in patientswith high circulating Lp(a) lipoprotein con-centrations, is particularly susceptible to lysisby streptokinase and thus reperfusion is moreoften evident in such patients. This may notbe as improbable as it at first seems becauseMao et al reported enhanced fibrinolysis in thepresence of high Lp(a) lipoprotein concentra-tions in vitro.'7 This possibility is, however,not supported by the angiographic part of ourstudy or the results of others.'4'6A second hypothesis to explain our electro-

cardiographic findings might be that theyresult, not so much from greater reperfusionof the myocardium in the patients with high

serum Lp(a) lipoprotein concentrations, butthat they represent a greater degree of reperfu-sion injury in patients with low serum Lp(a)lipoprotein concentrations. If this were thecase, its explanation might be that Lp(a)lipoprotein was acting to limit the extent ofbleeding into the perinfarction zone after dis-solution of the clot. Such bleeding leads to themorbid anatomical appearance of "red infarc-tion"38 and has been implicated as the causeof reperfusion injury (associated with pro-longed elevation of ST segments due to per-sisting "current-of-injury"), slower recoveryfrom myocardial injury, and eventuallyimpaired ventricular remodelling.39 40 Bothcoronary thrombolysis and red infarction canoccur spontaneously during myocardialinfarction, although they are more likely to doso if a thrombolytic agent has been given.Thus although Lp(a) lipoprotein may be

related to the risk of developing coronaryatheroma, our findings do not exclude a possi-ble beneficial effect during myocardial infarc-tion. This suggests caution in the use oftreatments aimed at lowering serum Lp(a)lipoprotein concentrations in patients at riskof coronary heart disease, because there maybe advantages as well as disadvantages from ahigh concentration of circulating Lp(a)lipoprotein. Any in vivo effects it might haveon coagulation are difficult to predict from invitro experiments. We believe that serumLp(a) lipoprotein concentrations should becorrelated with the clinical outcome in largertrials of thrombolytic treatment.This study was supported by an infrastructure award to PNDand a Research Fellowship to ADM from the NorthwestRegional Health Authority. We are grateful to the nurses anddoctors of the casualty department and the coronary care unit ofthe Manchester Royal Infirmary for their contribution to thiswork and our consultant cardiology colleagues Drs DJRowlands, LC, Cotter, G Howitt and all the general physi-cians at the Royal Infirmary who allowed us to study patientsunder their care. We are indebted to Miss S Arrol for technicalassistance and to Miss C Price for expertly typing the paper.

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