Incidence and significance coronary artery calcification · between calcification andsignificant...

British Heart journal, I974, 36, 499-506.

Incidence and significance of coronary arterycalcification

J. H. McCarthy and F. J. PalmerFrom the Departments of Pathology and Radiology, Prince Henry Hospital, Sydney, and the University ofNew South Wales, Australia

The incidence of coronary artery calcification was studied in 65 hearts obtained at necropsy.In cases over the age of 40 there was an incidence of coronary calcification of 79 per cent. The incidence

increases with age and is slightly more common in men. These lesions occur more commonly in the left coronarycirculation than the right. There is a strong association with aortic valve calcification.

Postmortem angiographic studies and microcopical examinations indicate that there is a close associationbetween calcification and significant arterial atheroma.

It is suggested that routine fluoroscopy should include a searchfor coronary calcification.

Calcification of arterial atheroma occurs in the cor-

onary arteries as it does in the remainder of thearterial tree. Such calcified coronary arteries are

occasionally noted on routine chest radiographs butare difficult to distinguish from normal mediastinalstructures and are easily confused with calcifica-tions in the chest wall, lungs, or other intracardiacstructures.These lesions are more easily shown by image

intensification fluoroscopy when the shape, size,position, and density of an abnormality can beviewed in high resolution in several planes and itsmovement relative to other structures clearly visual-ized. Tampas and Soule (I966) made a careful studyof the cardiac outline for coronary artery calcifica-tion during I097 routine chest screenings. The in-cidence of coronary calcification in patients over 40years of age was I5 per cent.

If coronary artery calcification were invariablyassociated with significant arterial stenosis or occlu-sion then routine chest screening with image intensi-fication would be a simple, safe, and valuable meansof detecting such patients. However, the patho-logical and prognostic significance of coronary

calcification appears to be in some doubt. Steiner,Sutton, and Grainger(i969), writing in a widely-usedradiology textbook states, 'In general there is no

correlation between the degree of coronary arterycalcification and the severity of coronary arterydisease.' Other authors have expressed similar

Received 23 October I973.

opinions (Adams, Abrams, and Ruttley, 1972;Vlodaver, Neufeld, and Edwards, I972).During 1972 we undertook a joint radiological-

pathological study into atherosclerotic coronaryheart disease which was subsequently incorporatedinto a thesis (McCarthy, I973). This study providedan opportunity to observe the incidence of radio-logically visible coronary artery calcification and toassess its significance by further radiological andmorbid anatomical studies. Sixty-five hearts re-moved at necropsy over an 8-month period werestudied. Case selection was random and largely con-secutive, and there were various causes of death, in-cluding trauma, respiratory disease, heart disease,intracranial catastrophe, and chronic renal disease.All age groups were represented but there wasnaturally a preponderance of older patients in anunselected necropsy series.

MethodThe heart was removed intact including the proximalaorta and main pulmonary artery. Radiographs weretaken in the anteroposterior and lateral planes. Forhearts of normal size a focal film distance I02 cm wasused and factors 36-40 kilovolts and 230 milliamps em-ployed. Appropriate variations in factors were made forenlarged hearts. Non-screen film was used without agrid.

After the plain radiographs the coronary arteries wereinjected with radio-opaque material using a modifica-tion of Schlesinger's original method (Schlesinger,I938). The injection mass of Laurie and Woods (r958)

on August 20, 2021 by guest. P

rotected by copyright.http://heart.bm

j.com/

Br H

eart J: first published as 10.1136/hrt.36.5.499 on 1 May 1974. D

ownloaded from

http://heart.bmj.com/

500 McCarthy and Palmer

FIG. I Normal coronary arteries outlined by contrast medium. Heart 'unrolled' for optimumdisplay.

was found to be the most satisfactory medium. Solidi-fication of the medium was obtained by placing the heartin iced saline. Further anteroposterior and lateral radio-graphs were obtained before dissection.The heart was opened by Schlesinger's method which

has the virtue of 'unrolling' the heart so that the wholecoronary arterial system is displayed and confusing over-lap of vessels avoided (Schlesinger, 1938). Furtherradiographs were obtained (Fig. I).

Microscopical and histological examinations of thecoronary arteries were made with particular reference toareas of apparent abnormality as indicated by the angio-graphic studies.

ResultsIncidence of calcificationCoronary artery calcification was present in 4I(63%) (Fig. 2) but there were no cases with calci-fication under the age of 40. The incidence overthe age of 40 was 79 per cent and there was seen tobe a significant increase in incidence with advancingage (Table). Only 2 of the cases over the age of 6o

TABLE Incidence of calcification related to age

Age groupsWhole 40+ 50+ 60+ 70+ 8o+series

63%' 79% 84%o 94% 93% io0%

had no calcification; they were both women aged6i and 70.The incidence in men (84%) was higher than in

women (75%). Since the average age of the menwas 6i and of the women 58 5, the figures are com-parable and confirm the slightly higher incidence inmen found in other series (Tampas and Soule, I966;Warburton et al., I968).The calcified lesions vary in appearance. Blanken-

hom and Stem (I959) defined the following types.i) Punctate lesions: discrete opacities of varying

size; may be linear, rounded, or irregular inshape. These occurred in 38 per cent.



j.com/

Br H


ownloaded from


Coronary artery calcification 5OI

2) Block calcification: oblong or linear densitiessufficiently large to outline the vessel, andindicating its size and direction. Theseoccurred in 36 per cent.

3) Double calcification. Linear and punctate den-sities outline both sides of the vessel but notfilling it completely. This type of lesionoccurred in 22 per cent.

4) Incomplete double calcification. The ve'sel isoutlined in one or both sides by small separatelesions of approximately i mm diameter(Fig. 2 to 5). This occurred in only 4 per cent.

It proved difficult to classify the findings in thisway as several or all types commonly occurred in thesame specimen.

Distribution of calcificationCalcified lesions ranged from a single, small plaquein one major branch to extensive calcification for allmajor branches (Fig. 2). The left coronary systemshowed a tendency for earlier and more extensivecalcification than the right coronary artery and therewere no examples of extensive calcification re-stricted to the right coronary artery. Most cases withpronounced calcification showed involvement of allmajor vessels (Fig. 2). The incidence ofpredominant

FIG. 2 Gross coronary calcification involving allproximal vessels.

vessel involvement was as follows: left coronaryand/or anterior descending, 47 per cent; right cor-onary, 30 per cent; circumflex, 23 per cent.The proximal 3 cm of the major vessel was the

predominant site of calcification in all cases, andthere were no cases of calcification or peripheralvessels without proximal involvement. Pathologicalexamination revealed a similar distribution ofatheromatous lesions.

Aortic valve calcificationBy using the air-filled shadow of the ascending aortaas a guide the aortic valve was easily identified inthe radiographs. In i6 cases calcification was de-tected in the aortic valve mainly at the junction ofthe cusps and valve ring. In only one had there beenclinical evidence of aortic valve disease. In all butone of the i6 cases aortic valve calcification wasassociated with coronary artery calcification (93%).There is, therefore, a strong relation between aorticvalve sclerosis and coronary calcification (Fig. 3a).

Mitral valve calcificationFive cases showed calcification in the mitral valvecusps or annulus. There was no correlation withcoronary calcification. Care was required to differ-entiate mitral annulus calcification from arterycalcification in the radiographs (Fig. 3a and 4).

Correlation with pathological findingsEach heart was carefully examined microscopicallyand areas of apparent abnormality in the coronaryarteries were removed for section. Areas suggestedas abnormal on the radiographs were also removed.The blocks of excised tissue were embedded in

gelatin which were then frozen and sections cut on afreezing stage microtome at 5-7 t± and floated onglass slides. Individual sections were stained todemonstrate fat, muscle cells, fibrin, mucopoly-saccharide, elastic tissue, and iron. A detailed studyof the disease process could thus be made(McCarthy, I973).For the purpose of histological correlation the

cases could be divided into three groups accordingto the radiographic findings.

A) No radiographic abnormalities (14 cases)All cases showed some evidence of histologicalabnormality even in the paediatric age group. Theinitial lesion of atheroma consisted of disruption ofthe internal elastic lamina with proliferation ofmuscle cells into the intima. Stains for lipid andcholesterol showed no evidence of these substancesin this type of lesion.



j.com/

Br H


ownloaded from



(a)

(b)F IG. 3 a) Aortic valve calcification (curved arrow),mitral valve calcification (closed arrow), and coronary

artery calcification (open arrow). b) Mitral valvecalcification again seen (open arrow). Tight stenosisin anterior descending and circumflex arteries at sitesof calcification.

B) Radiographic lumenal irregularity with-out calcification (io cases) Similar but morepronounced changes were found. There was con-siderable fragmentation of the internal elasticlamina with pronounced proliferation of fibroblastsand muscle cells within a thickened intima. Local-ized area of such fibromuscular plaques producednarrowing of the vessel lumen, which correlated wellwith the arteriographic appearances. Collagen andlipid could be detected in the intima at these sitesbut there was no evidence of cholesterol.

C) Calcification of vessels of varying severity(41 cases) All cases showed some degree of lumenalirregularity, varying from minimal vessel narrowingto complete occlusion. Calcification was confirmedmicroscopically in all cases where it was seen radio-logically.

Two types of calcification were found: i) Smalldeposits in fibromuscular plaques close to theinternal elastic lamina and without associatednecrosis. These were always found in suchatheromatous areas and were associated withminimal narrowing radiographically.2) Large deposits ( > o 5 cm) associated with franknecrosis within the intima. In these lesions theinternal elastic laniina had largely disappeared andthe media degenerated. The necrotic area con-tained considerable quantities of lipid and chol-esterol. These lesions were associated with morepronounced vessel narrowing ( > 70%), andrupture of the necrotic material into the vessellumen could be identified microscopically in somecases.The relative importance of degencration of

fibromuscular plaques and inundation of lipid andcholesterol from the blood stream was not deter-mined by this study.

Pronounced calcification was associated in allcases with severe atheromatous disease in the in-volved vessel. Thus, all cases with calcificationextending for over I cm of a vessel or with blockcalcification of several vessels demonstrated angio-graphic evidence of significant vessel stenosis orfrank occlusion (Fig. 4a and b).

In I9 hearts vessel occlusion was demonstratedangiographically and confirmed by dissection andmicroscopy. In i6 of these calcification was presentin the vessel wall at the site of occlusion (Fig. 2a,Fig. 3a and b, Fig. 5a and b and Fig. 6). The threecases without associated calcification were of a com-paratively younger age (44, 54, and 58 years), andpathological examination revealed recent acutecoronary thrombosis.



j.com/

Br H


ownloaded from


Coronary artery calcification 503

FI G. 4 Gross calcification in annulus of mitral valve (thin arrow). Double calcification in rightcoronary artery (wide arrows).

This study demonstrates a clear relation betweencalcification and arterial atheroma. Calcified lesionsof the order visible by fluoroscopy, i.e. os5 cm(Blankenhorn and Stern, I959) are associated withnecrotic lesions of the intima and vessel narrowing.The degree of vessel stenosis and the incidence ofcomplete vessel occlusion correlates well with theextent of radiologically visible calcification.

DiscussionCalcification in the wall of an involved vessel iscommonly demonstrated in atheromatous lesionsthroughout the arteriai system. Coronary arteryatheroma similarly undergoes calcification but thesignificance of this is disputed. It has been sug-

gested that calcification is a measure of the age of theatheromatous process and that it often occurs inelderly arteries without significant lumenal obstruc-

tion (Vlodaver et al., I972). Other authorities haveventured similar opinions (Adams et al., 1972).

Certainly the correlation with clinical cardiacischaemia is variable, dependent as it is on suchfactors as the degree of vessel stenosis, distribu-tion of lesions, arterial anatomical variations, andthe development of collateral circulation. However,this study has demonstrated that, even in theelderly, pronounced coronary artery calcificationis associated with severe atheroma and vesselstenosis above or approaching the critical level of50 to 75 per cent reduction of vessel calibre or frankvessel occlusion. There have been several studiesmade using methods similar to the present investi-gation whose authors have also concluded that thereis a strong correlation (Beadenkopf, Daoud, andLove, I964; Blankenhorn and Stem, i959; Eggen,Strong, and McGill, I965; jorgens et al., I965;



j.com/

Br H


ownloaded from



(a)

(b)

FIG. 5 a) Calcification in right coronary, anterior descending, and circumflex vessels. b) Com-plete occlusions in corresponding vessels demonstrated by contrast injection (wide arrows). Notethe collateral vessel supplying the distal circumflex artery (thin arrow).



j.com/

Br H


ownloaded from


Coronary artery calcification 505

FIG. 6 Complete occlusions in right artery and circumflex arteries (arrows). Stenosis alsoseen in anterior descending artery. The vessels were heavily calcified on the plain film.

Tampas and Soule, I966; Oliver et al., I964). It istherefore our contention that patients having pro-nounced coronary calcification are at risk from cor-onary occlusion, including those without clinicalevidence of ischaemic heart disease. Coronary cal-cification is therefore of important prognostic signi-ficance.

Osborn (I963) states, 'we have no means of sayingwhether the coronary arteries of the man in thestreet are good, bad or indifferent'. Screening of theheart for coronary calcification at routine fluoroscopyis a simple procedure that gives some measure of thesubclinical coronary atheroma in the general popula-tion. This finding in a comparatively young patientshould lead to further investigation.

Calcified lesions ofthe order ofo03 cm diameter aretheoretically visible fluoroscopically (Blankenhornand Stem, 1959). Random measurements of lesionsin our material show that the majority of calcifica-tions associated with stenosis obey these criteria.Many patients now attending hospitals are pre-

sently examined by image intensified fluoroscopyduring investigation of respiratory, cardiac, gastro-intestinal, urological, or vascular problems. Exam-ination of the cardiac silhouette for coronary calci-fication can be incorporated in these examinationswithout significantly increasing the duration of the

procedure or the amount of radiation. We supportthe plea (Tampas and Soule, I966; Warburtonet al., I968; Oliver, I970) that a search for coronarycalcification should be included in all such fluoro-scopic procedures.

ReferencesAdams, D. F., Abrams, H. L., and Ruttley, M. (I972). The

roentgen pathology of coronary artery disease. Seminarsin Roentgenology, 7, 3I9.

Beadenkopf, W. G., Daoud, A. S., and Love, B. M. (i964).Calcification in the coronary arteries and its relationship toarteriosclerosis and myocardial infarction. AmericanJournal of Roentenology, 92, 865.

Blankenhorn, D. H., and Stern, D. (I959). Calcification of thecoronary arteries. American Journal of Roentgenology, SI,772.

Eggen, D. A., Strong, J. P., and McGill, H. C. (I965). Cor-onary calcification: relationship to clinically significantcoronary lesions and race, sex, and topographic distribu-tion. Circulation, 32, 948.

Jorgens, J., Boardman, W. J., Damberg, S. W., Kinney,W. N.,and Kundel, R. R. (I965). The significance of coronarycalcification. AmericanJournal of Roentgenology, 95, 667.

Laurie, W., and Woods, J. D. (1958). Anastomosis in thecoronary circulation. Lancet, 2, 8I2.

McCarthy, J. H. (1973). The nature of the occlusion in cor-onary artery disease. Thesis for B.Sc., University of NewSouth Wales.

Oliver, M. F. (1970). The diagnostic value of detecting cor-onary calcification. Circulation, 41, 98I.



j.com/

Br H


ownloaded from



Oliver, M. F., Samuel, E., Morley, P., Young, G. B., andKapur, P. L. (1964). Detection of coronary-artery calci-fication during life. Lancet, I, 89I.

Osborn, G. R. (I963). The Incubation Period of CoronaryThrombosis. Butterworths, London.

Schlesinger, M. J. (I938). An injection plus dissection studyof coronary artery occlusions and anastomoses. AmericanHeart_Journal, 15, 528.

Sutton, D., and Grainger, R. G. eds. (I969). A Textbook ofRadiology, E. S. Livingstone, Edinburgh.

Tampas, J. P., and Soule, A. B. (I966). Coronary arterycalcification. American Journal of Roentgenology, 97, 369.

Warburton, R. K., Tampas, J. P., Soule, A. B., and TaylorH. C. (I968). Coronary artery calcification: its relationshipto coronary artery stenosis and myocardial infarction.Radiology, 9I, IO9.

Vlodaver, Z., Neufeld, H. N., and Edwards, J. E. (1972).Pathology of coronary disease. Seminars in Roentgenology,7, 376.

Requests for reprints to Dr. F. J. Palmer, Departmentof Radiology, Prince Henry Hospital, Little Bay, N.S.W.2036, Australia.



j.com/

Br H


ownloaded from


Incidence and significance coronary artery calcification · between calcification andsignificant...

Documents

Transcript of Incidence and significance coronary artery calcification · between calcification andsignificant...