comparison coronary angiographic findings acute chronic first

1938

Comparison of Coronary Angiographic Findingsin Acute and Chronic First Presentation of

Ischemic Heart Disease

Peter Bogaty, MD; Stephen J. Brecker, MD; Sarah E. White, RGN; Robert N. Stevenson, MD;Hassan El-Tamimi, MD; Raphael Balcon, MD; and Attilio Maseri, MD

Background. It is generally assumed that the clinical manifestations of ischemic heart disease occur

randomly on the same underlying pathological process. Therefore, coronary angiographic findings shouldbe similar whether the first presentation of ischemic heart disease is acute myocardial infarction or

uncomplicated chronic stable angina.Methods and Results. We studied 102 patients (men <60 years old, women c65 years old) presenting with

either acute myocardial infarction as first manifestation of coronary artery disease with a concomitantcoronary angiogram (55 patients; mean age, 50.2 years) or stable angina for at least 2 years with no

history, ECG, or left ventriculographic evidence of any acute event and with an angiogram performed atleast 2 years after initial symptoms (47 patients; mean age at symptom onset, 51.7 years). Theseangiograms were evaluated blindly for severity (number of vessels diseased, stenoses >50%o, occlusions),extent of disease (with an index derived by assigning a score of 0-3 per segment, depending on theproportion of lumen length irregularity and dividing the sum by the number of visualized segments), andpattern (discrete: three or fewer loci of disease never involving more than 50%7e of the length of any segmentor diffuse: anything exceeding this).

Patients with unheralded myocardial infarction had fewer vessels diseased, fewer stenoses andocclusions, and a lower extent index than those with uncomplicated stable angina (mean±SD of 1.3 ±0.8versus 2.1+0.8,p<0.001; 2.1±1.8 versus 3.9+1.8,p<0.001; 0.6±0.6 versus 1.0+0.9,p<0.02; and 0.6±0.5versus 1.2±0.5, p<0.001, respectively). A discrete pattern was present in 54.5% of patients withunheralded infarction and in only 8.5% of those with uncomplicated angina (p<0.001).

Conclusions. These very different angiographic findings suggest that unheralded acute myocardialinfarction and uncomplicated chronic stable angina do not occur randomly on a common atheroscleroticbackground but rather that additional factors, such as a varying propensity to thrombosis, maypredispose to one or the other of these two clinical syndromes. (Circulation 1993;87:1938-1946)KEY WORDS * angina * arteriosclerosis

angiography

solated epidemiological reports have suggested thatthe possible clinical presentations of ischemicheart disease may have different risk factor pro-

files.1-8 More recent prospective and cross-sectionalstudies have implicated procoagulant markers predis-posing to acute coronary disease.9-16 The traditionalview is that acute and chronic clinical manifestationsoccur randomly on the same underlying disease process.Clinicians, however, have often been intrigued by theobservation that acute coronary events can occur on abackground of quite limited angiographic disease,whereas other patients with far more extensive disease

From the Cardiovascular Research Unit, Royal PostgraduateMedical School (P.B., S.E.W., H.E.-T., A.M.), HammersmithHospital, and the Department of Cardiology (S.J.B., R.N.S.,R.B.), London Chest Hospital, London.

Presented in part at the 40th Annual Scientific Session of theAmerican College of Cardiology, Atlanta, Ga., March 6, 1991.

Address for correspondence: Peter Bogaty, MD, Quebec HeartInstitute, Hopital Laval, 2725 Chemin Ste. Foy, Ste. Foy, Quebec,Canada, G1V 4G5.

Received August 14, 1991; revision accepted February 4, 1993.

ischemia * vessels * myocardial infarction -

seem to remain stable for a long time. Patients maypresent with acute myocardial infarction as the firstevent in their history of ischemic heart disease and maythen enter a chronic phase. Other patients have aninitially chronic presentation that may later be punctu-ated by acute coronary events.17 Acute and chronicelements thus tend to be intermeshed in most patientsas a history of ischemic heart disease progresses. Con-sequently, if patients are studied a long time after theirinitial presentation, pathogenetic, clinical, and angio-graphic features that might be uniquely related to acuteor chronic coronary syndromes will be confounded andobscured, as suggested by the postmortem studies ofRissanen.'8These considerations led to the present study. We

speculated that if two pure subsets of coronary diseasecould be identified, one represented by unheraldedacute myocardial infarction and the other by uncompli-cated chronic stable angina, then a comparison of theirrespective angiographic features could have implica-tions regarding the substrate of acute and chronicischemic heart disease. Similar angiographic features

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Bogaty et al Angiographic Findings in Acute and Chronic Coronary Disease 1939

would suggest an identical common substrate, i.e., ath-erosclerosis and the random occurrence of acute eventson this substrate; dissimilar features would suggestinteraction with another pathological process, e.g., athrombogenic susceptibility. No study has yet addressedthis question. Because the conventional evaluation ofcoronary angiograms based on the number of signifi-cantly narrowed vessels provides limited information onangiographic appearance, we also used novel descrip-tive criteria to account not only for atheroscleroticdisease severity but also for its extent as well as toidentify different arteriographic patterns of disease.This study reveals striking differences in the angio-graphic findings in these two ischemic syndromes.

MethodsSelection CriteriaThe consecutive discharge summaries of all patients

hospitalized in two cardiovascular units over a 13-month period were scanned. The two hospitals, inGreater London, are tertiary care centers, with referralsfrom outlying areas constituting about half the admis-sions. The patient composition reflects the heteroge-neous socioeconomic and ethnic nature of the basepopulation. The study commenced in April 1989. Itincluded 10 months retrospectively and 3 months pro-spectively. The summaries of those patients undergoingcoronary arteriography during that hospitalization(n= 2,605) were examined to see whether they appearedcompatible with one of the following two sets of criteria.

Unheralded acute myocardial infarction. 1) Men had tobe .60 years old and women .65 years old at the timeof this presenting event. 2) The diagnosis of myocardialinfarction required the presence of at least two of thefollowing: characteristic chest pain, a cardiac enzymerise greater than twice the upper normal limit, andcompatible ECG changes lasting >48 hours. 3) Myocar-dial infarction had to be the first manifestation ofischemic heart disease in these patients. A prodrome ofa maximum 4 weeks of new-onset chest pain waspermitted. 4) Coronary arteriography had to be per-formed within 3 months of infarction.

Uncomplicated chronic stable angina. This requiredthat 1) men be 560 years old and women <65 years oldat the time of first onset of angina. 2) A minimum 2-yearhistory of typical stable angina with a positive exercisetest was necessary. 3) No history of any acute event,defined as unstable angina or acute myocardial infarc-tion, from the time of first symptom onset for at least 2years was allowed. Unstable angina was defined asprolonged chest pain or a sharp and significant changein the pattern of established angina or new-onset anginawith symptoms at rest or on minimum exertion notculminating in myocardial infarction. 4) No Q waves, noR/S >1 in lead V1 or V2, and no left bundle branchblock on the resting ECG were allowed. 5) No segmen-tal akinesis or dyskinesis on left ventriculography wasallowed. 6) Coronary arteriography had to be per-formed at least 2 years after initial symptoms, and therehad to be no history of any acute event up to andincluding the time of this angiogram.The hospital records of those patients whose dis-

(n=412), and if they remained compatible (n=165),these patients were then contacted either by telephoneor by visit, and a structured questionnaire was adminis-tered. Four of these patients had already died, butinformation judged satisfactory could be obtained forthree of them. Six other patients could not be reachedand were excluded. Of the 158 patients reaching this lastphase, 64 presented with infarction and 94 with angina.The purpose of the questionnaire was to confirm theexactitude of the clinical history, specifically to ensurethat those presenting with myocardial infarction had nopreceding history suggestive of angina or of a prioracute coronary event (nine of the 64 were eliminated)and that those presenting with angina had no history,however brief, compatible with an acute coronary event(47 of the 94 were eliminated). This large number ofexclusions in the angina group at the interview stage wasa result of the frequent finding on close questioning ofsymptoms highly suggestive of instability, particularly atthe inaugural history (usually prolonged chest pain atrest or recurrent pain on minimal activity). Final selec-tion of patients was carried out in committee with theparticipating physicians in such a way that the latterremained blinded to the patients' identity. The targetrecruitment figure for each subset was 50 or 60 patients.This figure was first reached for myocardial infarction,so subsequent consecutive recruitment for angina onlycontinued until a comparable number was attained.

Angiographic CriteriaDuring this recruitment phase, coronary angiograms

unrelated to the study were examined. Initially, sincethe conventional criterion of number of vessels diseasedprovides limited information on angiographic appear-

ance, methods previously described for scoring coronaryatherosclerosis were considered.19-23 Because thesewere found to be either too restrictive or too cumber-some and do not identify particular patterns of disease,a more comprehensive analysis of coronary angiogramsbased on three descriptive concepts- severity, extent,and pattern-was developed. Severity pertains exclu-sively to degree of narrowing ("transverse disease") andwas evaluated by counting the number of vessels dis-eased, stenoses, and occlusions. Extent, as distinct fromseverity, considers the proportion of each coronarysegment that appears abnormal ("longitudinal dis-ease"). Pattern implies a global appreciation of athero-sclerotic involvement; a discrete pattern and a diffusepattern could be identified.Under severity, the three indexes considered were

thus 1) vessels diseased, classically the number of majorepicardial vessels with 270% narrowing of the lumendiameter. The maximum number of vessels diseased wasthree. A left main stem stenosis of 250% counted astwo vessels.24 2) Stenoses, the total number of .50%narrowings on all the vessels of the angiogram. A longstenosis whose length attained twice the normal lumendiameter was counted as two stenoses. A maximum ofthree stenoses was permitted per coronary arterialsegment (see below). Nonocclusive stenoses were clas-sified as concentric, eccentric type I, or complex (eccen-tric type II or multiple irregularities) according to the

charge summaries appeared compatible with one or theother of these sets of criteria were then examined

criteria of Ambrose et al.2.5 3) Occlusions, which alsoincluded subtotal occlusions if there was clearly delayed



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1940 Circulation Vol 87, No 6 June 1993

a. stenoses=O; extent score=1.

b. Stenoses=O; extent score=3.

C. stenoses=1; extent score=2.

d. stenoses=2; extent score=3.

FIGURE 1. Illustrative schema of stenoses and extent scoreas applied to one coronary artery segment. Stenoses are thetotal number of narrowings 250%. If no abnormality isapparent, the segment extent score is 0. A segment scores 1 forextent if any abnormality is confined to 10% or less of itslength; the extent score is 2 if the abnormality affects morethan 10% up to 50% of its length; the extent score is 3 if theabnormality affects more than 50% of the segment's length.

or incomplete antegrade flow. The quality of collaterals(absent-to-poor or good-to-excellent) was noted.The extent of atherosclerosis was quantified in a score

that was normalized to an extent index. This was donesimply and visually by assigning a score of 0-3 persegment of the coronary arterial tree. A segment wasscored 0 if it appeared angiographically normal; 1 ifc 10% of its length appeared abnormal (narrowedand/or irregular); 2 if > 10% up to 50% of its length wasabnormal; and 3 if >50% of its length was abnormal. Ifa segment was occluded or suboccluded with compro-mised antegrade flow, it was arbitrarily given a score of2 (or 3 if any abnormality proximal to the occlusioninvolved more than half the nonoccluded portion of thesegment), and segments distal to it were not scored. Theextent score was the total score of the 15 segments ofthe coronary tree. The division of the angiogram intosegments was a slightly modified version of the Ameri-can Heart Association classification.26 A dominant rightcoronary artery had five segments: proximal, mid, distal,posterior descending artery, and posterior left ventric-ular. The left main stem was one segment. The leftanterior descending artery had five segments: proximal,mid, distal, and two for the diagonals. The circumflexartery (of a nondominant left coronary artery) had foursegments: proximal, distal, obtuse marginal, and an-other marginal. The extent index was the extent scoredivided by the number of segments that could beproperly visualized by antegrade flow. Thus, the extentindex could range from 0 (score of 0) to a maximum of3 (score of 45 divided by 15 segments). An illustrativeschema of stenoses and extent score appears in Figure 1.For the pattern concept, a discrete pattern was one in

which there was a maximum of three loci of disease orabnormality never involving more than half the lengthof any segment, with the rest of the angiogram having awholly normal appearance. An occlusion could count asa locus of a discrete pattern provided that, if there wasany abnormality just proximal to it, this did not involve

ment. If a locus appeared astride two segments, it couldcount as the locus of a discrete pattern if the total lengthof the abnormality involved 25% or less of the combinedlength of the two segments. Exceptionally, the left mainstem, because of its short length, could be considered asa locus of a discrete pattern even if its entirety appeareddiseased. A diffuse pattern was anything exceeding thecriteria for a discrete pattern, either more than threeloci of disease and/or any involvement exceeding 50% ofthe length of any segment.Once these descriptive criteria were defined and

practiced, they were then applied to the constitutedstudy group. Each angiogram was evaluated indepen-dently by two observers blinded to all clinical dataincluding the left ventriculogram. If there had beenthrombolysis or angioplasty during angiography (in caseof a myocardial infarction presentation), this part of thefilm was removed before the angiogram was presentedto the observers. After initial evaluation, each angio-gram was studied jointly to reach agreement. Whenagreement was not possible for the criteria of severity(vessel disease 270% narrowing or stenosis 250%narrowing), a computerized contour detection system(CAAS, Pie Data Medical, Holland) was applied, aspreviously described.27 This was done for 16 of 171lesions of vessel disease (9%) and 35 of 293 stenoses(12%). Reproducibility of the extent scoring system wasgood, with 75% of the scores of two observers withinone point of each other, 90% within two points, and95% within three points. When agreement was notpossible regarding the criteria of extent of disease (13 of102 angiograms), a third observer intervened. Regard-ing pattern of disease, it was found that all angiogramscould be quite easily and quickly classified as having adiscrete or diffuse pattern (Figure 2). The two observersinitially disagreed about pattern in 12 of 102 angio-grams, and a third observer intervened in nine of these.The data were analyzed only after final angiographicevaluation of the entire study group.

Risk Factor CriteriaConventional risk factors were examined from hospi-

tal records, rechecked by direct questioning, and com-pleted with data from personal physicians and, whereappropriate, from hospital follow-up. Recent smokerswere those who had been smoking five or more ciga-rettes a day for at least 3 months in the year precedingangiography. Past smokers were those who had con-sumed five or more cigarettes a day for a year or moreat any time (within 20 years) up to 1 year beforeangiography. Serum cholesterol was measured by enzy-matic assay. For myocardial infarction patients, it wasdetermined on admission and at least 2 months later.For all subjects, the highest value found was retained.Hypertension required a satisfactory prior diagnosis oran arterial pressure .140/90 mm Hg on three occasionsexcept during angiography or an evolving infarction.Diabetes mellitus required either a satisfactory priordiagnosis or the presence of at least two fasting plasmaglucose values .140 mg/dL. For myocardial infarctionpatients, this had to be at least 1 week after infarction.A family history was positive if any first-degree relativehad sustained an acute or chronic manifestation of

more than half the nonoccluded portion of that seg- coronary disease before the age of 65 years.



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FIGURE 2. Coronary angiograms showing examples of discrete and diffuse patterns of disease. Top panels: Right and leftcoronary arteriograms showing a discrete pattern in a patient with unheralded acute myocardial infarction. This angiogram hasa normal appearance except for localized disease of the distal half of the proximal segment of the right coronary artery (arrow).Bottom panels: Diffuse pattern in a patient with uncomplicated chronic stable angina. Both right and left coronary arteriogramsshow extensive disease involvement.

Statistical AnalysisResults are expressed as mean±SD. Comparisons

were made by the unpaired two-tailed t test for normallydistributed values; otherwise, the two-tailed Mann-Whitney U test corrected for ties was applied. The x2test with continuity correction was used to analyzedifferences in proportions when the smallest expectedvalue was >5; otherwise, the Fisher exact test was used.Correlations between variables were tested by simpleregression analysis. A value of p<0.05 was consideredstatistically significant.

ResultsThe study group consisted of 102 patients. This

constitutes <5% of all patients with coronary artery

disease undergoing catheterization during this sameperiod. Of this group, 55 patients (80% men) fulfilledthe criteria for unheralded myocardial infarction (twothirds had Q waves) and 47 (78.7% men) for uncompli-cated chronic stable angina. The age of the infarctiongroup was 50.2±8.3 years (range, 32-63 years); of theangina group, it was 51.7+5.6 years (range, 39-60years) at the time of symptom onset and 56.7±+6.2 yearsat the time of cardiac catheterization. The subjects withstable angina had thus been symptomatic for almost 5years before angiography. The indications for coronaryangiography in the infarction patients were residualischemia (36%) with angiography often performed dur-ing that hospitalization, a research protocol requiringangiography before starting thrombolysis (38%), and



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unrelated reasons at the discretion of the consultantcardiologist (26%).When the angiograms of these two cohorts were

evaluated in terms of the standard criteria of number ofvessels diseased, the infarction group had 1.3±0.8 com-pared with 2.1±0.8 vessels diseased for the anginagroup (p<0.001) (Figure 3). The distribution of zero-,

one-, two-, and three-vessel disease was 9.1%, 61.8%,18.2%, and 10.9%, respectively, in the infarction group;it was 0%, 25.5%, 38.3%, and 36.2%, respectively, in theangina group. When the other two indexes of severity(stenoses and occlusions) were considered, the resultswere comparable. Patients with unheralded myocardialinfarction had 2.1±1.8 stenoses and 0.6±0.6 occlusions,whereas those with uncomplicated stable angina had3.9±1.8 stenoses (p<0.001) and 1.0±0.9 occlusions(p<0.02) (Figure 3). The distribution of lesions accord-ing to concentric, eccentric type I, and complex mor-phology was 25.6%, 59.8%, and 14.6%, respectively, inthe infarction subset and 21.5%, 75.4%, and 3.1%,respectively, in the angina subset. Of the myocardialinfarction patients, 22 (40%) had received thrombolytictherapy before angiography, and 10 of these (45.5%)had an occluded infarct-related artery; of the 33 (60%)who did not receive thrombolytic therapy at the time ofthe study angiogram, 19 (57.6%) had an occludedinfarct-related artery. Therefore, the impact of throm-bolysis on the number of occlusions in the infarctiongroup was not very important. Of the infarction patientswith occlusions, 39.5% had good-to-excellent collater-als; the corresponding figure for angina patients was95.7%.The findings for extent of disease were similar to

those for severity (Figure 3). The extent index of thosewith infarction was 0.6±0.5; of those with angina, it was1.2±0.5 (p<0.001). The indexes of severity, vesselsdiseased, stenoses, and occlusions correlated highly witheach other (p<0.001 for all), and all correlated highlywith the extent index (p<0.001 for all).A diffuse pattern was extremely frequent in the

uncomplicated stable angina subset (91.5%); a discretepattern predominated in the unheralded infarction sub-set (54.5%) (Figure 3). Of the 34 patients with a discretepattern, this involved only one locus of disease in 50%,two loci in 32.4%, and three loci in 17.6%.The angiographic findings in patients with uncompli-

cated stable angina with respect to the duration of their

60

50

40

30

20

10

0

PatternFIGURE 3. Bar graphs show-ing severity, extent, and patternof coronary artery disease com-pared in patients with unher-alded acute myocardial infarc-tion and uncomplicated chronicstable angina. Solid bars, unher-alded acute myocardial infarc-tion; hatched bars, uncompli-

Z57 cated chronic stable angina.*p<0.001; **p=0.02.

anginal symptoms are summarized in Table 1. Subjectswith a 2-year history of angina are compared with thosewith a history of 27 years. The former were 54±4.6years old at the time of angiography; the latter, 60.7+ 3.7years old. Despite these differences in age and durationof angina, the findings are not significantly different.As for risk factors (Table 2), serum cholesterol levels

and the proportion of those with a positive familyhistory were comparable in the two groups. A recentsmoking history was obtained nearly twice as often inthose with myocardial infarction than in those withstable angina (60% versus 31.9%, p<0.01). When pastand recent smoking history were considered, however,the proportions were comparable. Hypertension wasfound twice as frequently in angina patients (63.8%versus 30.9%, p<0.01). There was one patient withdiabetes in the infarction group and seven such patientsin the angina group (p=0.02).None of the indexes of severity correlated with serum

cholesterol either in the angina or the infarction sub-sets. The extent index, however, did correlate withserum cholesterol in the stable angina group (r=0.4,p=0.015) but not in the myocardial infarction group(r=0.24, p=0.11).None of the unheralded infarction patients were

taking aspirin on a regular basis before their event. Ofthe angina patients, fewer than half (20 of 47) were onregular aspirin therapy at the time of angiography. Onlyfour angina patients and no infarction patients weretaking lipid-lowering agents.

DiscussionThe major finding of this study is the markedly

different angiographic appearance of unheralded acutemyocardial infarction compared with uncomplicatedchronic stable angina. Whether the standard criterion ofnumber of vessels diseased was used or the number of

TABLE 1. Angiographic Findings: 2-Year Versus >7-YearHistory of Uncomplicated Stable Angina

2-Year history .7-Year history(n=12) (n=13) p

Vessels diseased (No.) 2.2+0.8 2.1±0.8 0.8Stenoses (No.) 3.8±1.3 4.2±2.0 0.6Occlusions (No.) 0.8±1.0 1.3±0.9 0.1Extent index 1.12±0.46 1.28±0.44 0.4



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Bogaty et al Angiographic Findings in Acute and Chronic Coronary Disease

TABLE 2. Risk Factor Profiles of the Two Patient Groups

Unheralded acute Uncomplicated chronicmyocardial infarction stable angina

(n=55) (n=47)Age at onset (years±SD) 50.2±8.3 51.7+5.6Men (%) 80 78.7Serum cholesterol (mmol/L+SD) 6.6±+1.8 (256±70) 6.9±1.3 (267±50)Arterial hypertension (%) 30.9 63.8*Recent smoking history (%) 60 31.9*Recent or past smoking history (%) 65.5 61.7Diabetes mellitus (%) 1.8 14.9tPositive family history (%) 53.7 53.2

Numbers in parentheses are concentrations in mg/dL.*p<0.01; tp=0.02.

stenoses or occlusions or an index of disease extent, theresults are concordant and discriminate clearly betweenthe two groups. The difference is even more strikingwhen pattern of disease is considered. A discrete pat-tern is frequent in and characteristic of unheraldedmyocardial infarction; a diffuse pattern is almost therule in uncomplicated chronic stable angina.These contrasting angiographic findings are intrigu-

ing. On the one hand, atherosclerosis may diffuselyinvolve the epicardial coronary arteries and even prog-ress to total occlusion without causing clinically appar-ent episodes of instability or signs of infarction. On theother, sudden occlusion can cause infarction in thepresence of very limited angiographically detectableatherosclerosis. It is the study of patients at the time offirst presentation of ischemic heart disease that iscrucial to a recognition of these distinct patterns. Thepremise of this study was that if acute and chronic firstclinical presentations of ischemic heart disease occurredrandomly on the same underlying pathological process,similar angiographic findings would be expected. Thesedissimilar findings suggest that, in addition to slowlyprogressive coronary atherosclerosis, another patholog-ical process and another constellation of risk factors,possibly related to increased thrombogenicity, could beinvolved, accounting for these different angiographicappearances and clinical presentations.

Comparison With Other StudiesIt has not been generally appreciated that myocardial

infarction and stable angina as pure isolated presenta-tions might possess different angiographic features. Weare not aware of any other coronary arteriographicstudy that has attempted to characterize patients ac-cording to rigorous criteria of exclusively acute andexclusively chronic coronary disease. As a result, withthe exception of the morphological analysis of certainindividual lesions,25,28,29 the angiographic impression ofacute and chronic coronary disease tends to be that ofan undifferentiated entity. Pathological reports as wellas angiographic studies, few of which are stratifiedaccording to prior clinical status and which often have aselection bias in favor of advanced disease, have rein-forced the tendency to assume that coronary arterydisease is generally severe when its clinical manifesta-tions appear, whatever they might be.30-39

It has already been suggested, however, that angio-graphic appearance might differ depending on clinical

presentation. In a pathological study, Rissanen18 ob-served that atherosclerosis was more severe in patientswho had had symptomatic heart disease and in oldmyocardial infarction and least severe in those withsudden death as the first manifestation of coronarydisease. When infarction is the initial presentation ofcoronary disease, it appears more often associated withsingle-vessel involvement, whereas angina before infarc-tion may be more frequently associated with multivesseldisease.40,41 Roberts et a142 found a higher incidence ofmultivessel disease in chronic angina than in new-onsetangina. Single-vessel disease and poor collateral floware the most frequent angiographic findings in patientswho develop a ventricular aneurysm after a first anteriormyocardial infarction.43The relatively low number of occlusions in the myo-

cardial infarction patients can be only marginally attrib-uted to thrombolysis (see "Results") and more tospontaneous recanalization, because angiography wasperformed within 3 months of infarction. But it is thelarge number of occlusions in the stable angina groupthat is intriguing, because we had gone as far as possibleto exclude acute coronary events in this cohort. Theconsistent presence of a developed collateral circulationand of preserved ventricular function suggests gradualrather than abrupt development of occlusion in chronicstable angina patients. Pathological studies lend supportto this observation. In a pioneering work, Blumgart etal44 noted coronary occlusions in the absence of necro-sis, fibrosis, or a clinical history and with evidence of adeveloped collateral circulation. Rissanen18 found cor-onary occlusions in 12% of a control group without anymyocardial signs of disease. Hangartner et a145 foundrecanalized vessels in 10 of 16 patients with stableangina in the absence of infarction.

Nature of Cohorts and Potential LimitationsStringent clinical criteria were applied so that the two

cohorts might constitute, as far as possible, pure subsetsof acute and chronic coronary disease. The interviewquestionnaire was structured to make doubly certain ofthe absence of "contaminating events" in either group.In the angina subjects, the ECG criteria and the re-quirement for no dyskinesia or akinesia on left ventric-ulography were intended to exclude, as far as possible,the occurrence of unsuspected myocardial infarction.Hypokinesia was not an exclusion criterion because it isopen to interpretation variability and might also reflect

1943



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a hibernating state.46 In spite of these precautions, theoccurrence of prior silent or inapparent acute coronaryevents cannot be excluded in the stable angina cohortnor prior silent ischemia in the unheralded infarctioncohort. Notwithstanding these possibilities, the angio-graphic findings in the two groups differ quite markedly.

Because this is an angiographic study, in each case thereason for this procedure was reviewed to see whetherthese patients are representative of unheralded infarc-tion and chronic angina patients in general. In 36% ofthe infarction patients, angiography was performedbecause of possible residual ischemia, a percentagewithin the limits observed in other studies.47 In 38%,angiography was carried out acutely under a researchprotocol requiring arteriographic documentation beforethrombolysis. The entry criteria of this protocol weresufficiently wide as to cover a representative sample ofpatients sustaining a myocardial infarction. In 26%,angiography was performed at the discretion of theattending physician for reasons present in general clin-ical practice, the relatively young age of a patient, anon-Q-wave infarction, left ventricular dysfunction, oran institutional policy favoring angiography after infarc-tion. In the angina group, angiography was never per-formed in the context of an unstable state. Almost halfof these patients were referred from areas removedfrom tertiary facilities. Had they originated from urbancenters, it is likely that they would have come tocatheterization earlier. However, this was preciselywhat was needed for the purposes of this study, an"undisturbed" stable subset that could give some idea ofwhat chronic morphology might be.

It may be that two additive confounding factors,greater age and a longer clinical history, contributed tothe more severe and extensive disease found in subjectswith stable angina. Thus, although the ages of the twocohorts were comparable at the time of onset of symp-toms, the stable angina group was 6 years older and hadbeen symptomatic for almost 5 years at the time ofangiography. An indirect way of considering this prob-lem is to compare the ages (see "Results") and angio-graphic findings of those patients with a 2-year historyof stable angina with those with a history of >7 years ofangina (Table 1). Despite the differences in age (>6years) and duration of angina, there is only a very weaktrend to more severe and extensive disease in the lattergroup. Thus, although the effects of age and duration ofclinical history cannot be ruled out, it is unlikely thatthese factors might account for the major differences inangiographic findings between the infarction and anginacohorts.Although angiography underestimates coronary dis-

ease, especially in the presence of diffuse smooth ath-erosclerotic narrowing,48-50 the dissimilar findings in thetwo patient groups strongly suggest significantly differ-ent disease involvement.Whereas the large number of ex-smokers in the

angina group suggests risk factor modification afterdiagnosis, a recent smoking history is frequently elicitedin the infarction group, suggesting a potential trigger foracute events. This has already been evoked in previousstudies6'7 and is indirectly suggested by the link betweencigarette smoking and myocardial infarction with angio-graphically normal coronary arteries.51,52 Although thedissimilar risk factor profiles noted in these two patient

groups are provocative, this must be tempered by thelimited numbers as well as by the retrospective nature ofthe data collection.

ConclusionsThe study of patients at the ends of the clinical

spectrum of ischemic heart disease has revealed markeddifferences in severity, extent, and pattern of coronarydisease. At one end of the spectrum, diffuse atheroscle-rosis can progress to critical stenosis and even toocclusion without provoking infarction or clinically ap-parent episodes of instability. At the other end, myo-cardial infarction abruptly inaugurates clinical ischemicheart disease most often in coronary arteries discretelyaffected by angiographically detectable atherosclerosis.Although it is well accepted that the mechanisms re-sponsible for stable and unstable coronary syndromesare different,53-56 the contrasting angiographic features(and dissimilar risk factor profiles) found in these twopure ischemic syndromes suggest that, in addition, thepathogenetic substrate on which these mechanismscome into play might not be an undifferentiated entity.These findings lend support to the concept that al-though atherosclerosis constitutes a strong predisposingfactor for acute coronary disease, acute disease may beneither an inherent and inevitable consequence nor arandom expression56 of atherosclerosis. Studies alreadysuggest that the occurrence of acute coronary events inchronic ischemic heart disease patients is difficult topredict from clinical parameters57 or from the severityof coronary stenoses.58-60 It is perplexing why somesubjects with coronary atherosclerosis appear "protect-ed" for at least some time from acute disease, whereasin others, myocardial infarction occurs precociously onlimited angiographically detectable atherosclerosis.Factors in addition to the presence of atherosclerosisthat may involve differences in genetic susceptibility6'and in acute (e.g., thrombogenic) as opposed to chroniccoronary disease risk factors9-'6 could interact in somedecisive manner. Work at these two ends of the spec-trum of ischemic heart disease may provide clues tothese intriguing mechanisms.

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P Bogaty, S J Brecker, S E White, R N Stevenson, H el-Tamimi, R Balcon and A Maseriischemic heart disease.

Comparison of coronary angiographic findings in acute and chronic first presentation of

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