- Email: [email protected]
Angiographic severity of coronary narrowing is a surrogate marker for the extent of coronary atherosclerosis
Angiographic Severity of Coronary N arrowing Is a Surrogate Marker for the Extent of Coronary Atherosclerosis Akihiro Nakagomi,
MD, David S. Celermaier,
MB, BS, PhD, Thomas Lumley, MSC,
and S. Ben Freedman, MB, BS, PhD Most acute coronary events occur because of narrowings at sites of angiographically minor plaque. Despite this, angiogmms are reported in terms of the number of coronary arteries with severe narrowings. Disease severity is correlated with prognosis, but this may simply be due to a strong positive correlation between the severity and extent of coronary atheroma. We therefore aimed to assess the relation between the severity and the extent of coronary atherosclerosis. Coronary angiograms of 350 consecutive patients referred for elective cardiac catheterization were analyzed. Two independent observers calculated the number of arteries with ~70% stenosis, a disease severity score, and an extent score (percentage of the coronary artery length with any luminal irregularity). There were no obstructive &noses in 123 patients (35%); 91 (26%) had 1-vessel disease,
81 (23%) had 2-vessel disease, and 55 (16%) had 3vessel coronary artery disease. The median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8), and the median extent score was 66% (lower, upper quartile 32,83; range 0% to 100%). There was a strong linear relation between severity score and extent score (r = 0.62, p
orbidity and mortality in patients with coronary artery disease are related to the number M of major epicardial arteries with 250% or 270%
were scored for extent and severity of coronary artery disease, as detailed later. The indications for cardiac catheterization were stable angina pectoris in diameter reduction. l-5 The method of scoring coro- 146 (42%)) unstable angina in 94 (27%)) prognostic nary angiograms for the number of arteries showing reasons following myocardial infarction in 32 (9%)) coronary stenoses has been widely accepted, in part assessment of valvular disease in 32 (9%)) atypical because of the prognostic value of this score. Despite chest pain in 22 (6%)) and other reasons in 24 (7%). this, acute coronary events are usually due to arterial Patients were excluded if they had a history of corocclusion or thrombotic complication at sites of pre- onary artery surgery or coronary angioplasty. viously minor disease.6-g In patients who have had Coronary angiogmphy: Coronary angiography was coronary angiograms performed on 2 occasions, total performed by the standard Judkins or Sones techocclusion of a previously severe stenosis is likely to nique and was recorded on 35 mm tine films or digbe clinically silent, whereas unstable angina or acute ital/analog laser disc. Coronary angiograms were inmyocardial infarction is more likely to have resulted terpreted visually using multiple orthogonal views. from progression of a relatively minor plaque.6-g Coronary scores: Coronary angiograms were Major clinical coronary events may therefore be re- scored by 3 techniques. lated better to the extent of minor plaque in the corNUMBER OF DISEASED ARTERIES: This score onary arteries than to the number of obstructive le- counted the number of coronary arteries (left antesions.” In this study, we estimated the extent of rior descending artery, left right circumflex and arcoronary atherosclerosis using a novel extent score tery) with 270% diameter stenosis (i.e., scores rang(percent of the coronary tree covered by any irreg- ing from 0 to 3). Left main stenosis 250% was ularity) l1 and explored the relation between this ex- scored as l-vessel disease. tent score and more traditional measures of coronary SEVERITY SCORE: In this score, a value of 1 was artery disease severity. given to any of 15 arterial segments (as defined by the American Heart Association)” that contained METHODS 270% diameter stenosis, giving a potential score Subiectsz Coronary angiograms of 350 consecutive patients referred for elective coronary angiography range from 0 to 15. This score therefore gives a more complete measure of disease severity than simply the number of major arteries involved. From the Department of Cardiology, Royal Prince Alfred Hospital, Camoerdown. Svdnev; and The NHMRC Clinical Trials Centre. UniEXTENT SCORE:We developed this score previversi$ of Sydney: Sydhey, Australia. Manuscript received November ously to estimate the percentage of the coronary ar17. 1995: revised manuscriot received and acceoted Aoril 1 1996. tery length involved by atheroma.” Briefly, the pro‘Addrek for reprints: Pkfessor S. B. FreedAan, depariment of portion of each vessel involved by any atheroma, Cardiology, Concord Hospital, Hospital Road, Concord, Sydney, identified by luminal irregularity, was multiplied by NSW, 2 139, Australia. 5
16
0 1996 by Excerpta Medico, All rights reserved.
Inc
0002-9 149/96/$15.00 PII SOOO2-9149(96)00355-4
r=O.GS y
I
0
20
40
Extelrt
80
60
100
Score (%I
FIGURE 1. Relation between he number of diseased arteries with 270% stenosis and extent score. The data poink represent mean + 2 SEM (95% confidence intervals).
in an approximately linear fashion. This linear relation was then used to estimate the SD as a function of disease extent for each measurement. The reciprocal of the variance (the precision) was then used as a weight for each observation in the weighted analyses. A scatterplot smoother I4 was then applied to these data. This gives an estimate of the relation between the 2 variables without making assumptions about the form of a model. The curve was relatively straight up to about 80% disease extent and then rose more sharply for more extensive disease. A formal test of this behavior was carried out by constructing a 2-phase regression curve, in which the relation is assumed to be linear but with a change in slope at some unspecified point. This intersection point was chosen by minimizing the weighted residual sum of squares from the fitted 2-phase regression model. A 95% confidence interval was calculated using an F test.15
RESULTS a factor for each vessel: left main artery, 5; left anterior descending artery, 20; main diagonal branch (or branches), 10; first septal perforator, 5; left circumflex artery, 20; obtuse marginal artery and posterolateral branch together, 10; right coronary artery, 20; and main posterior descending branch, 10. When the major lateral wall branch was a large obtuse marginal or intermediate vessel with no posterolateral branches, these were given a factor of 20, and the left circumflex artery a factor of 10. When a vessel was occluded and the distal vessel was not fully visualized by coronary collateral flow, the proportion of the vessel not visualized was given the mean score of the remaining arteries. The scores for each vessel or branch were added to give a total score out of 100. The number of arteries and severity scores were based on the consensus opinion of 2 experienced angiographers. The extent score was obtained independently by a third angiographer. The interobserver error of extent score (mean unsigned difference between 2 estimates + SD) has been reported previously to be 5 + 4% in our laboratory.” In this series, a second blinded extent score was measured by the same observer 1 month after the first reading in 40 randomly selected cases; the intraobserver error was 2 + 2%. Statistical analysis: Data were analyzed using the Statistical Programme for Interactive Data Analysis (SPIDA) .I3 All descriptive data are expressed as mean 5 SD. In the variability studies, inter- and intraobserver variabilities were expressed as the mean of the unsigned differences between paired readings 2 SD of the mean difference. Standard linear regression was used to assessthe relation between the number of arteries with ~70% stenosis and extent score. For comparison of the severity score with the extent score, the data were divided into 5 groups according to extent score (0 to 20%, 21 to40%, 41 to 60%, 61 to 80%, 81 to lOO%), and the SD of the severity score was calculated for each group. These SDS increased with disease extent CORONARY
Subjects: There were 249 men (71%) and 101 women (29%) (mean age 60 ? 10 years [range 30 to 851). One hundred nineteen (34%) had never smoked cigarettes, 32 (9%) were current smokers, and 199 (57%) were former smokers. The average lifetime smoking was 22 ? 10 pack-years (range 2 to 140). There were 45 patients (13%) with diabetes mellitus (all had type 2 or noninsulin-dependent diabetes), and 118 (34%) had a history of systemic hypertension. One hundred subjects (29%) had a family history of premature vascular disease. In total, 152 subjects (43%) gave a history of hypercholesterolemia, although only 48 ( 14%) were taking lipidlowering drugs. Angiographic results: One hundred twenty-three patients (35%) had no arteries with 270% stenosis; 91 (26%) had l-artery, 81 (23%) had 2-artery, and 55 ( 16%) had 3-artery coronary disease. The median number of diseased arteries was 1 (lower, upper quartile 0,2; range 0 to 3 ) , the median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8)) and the median extent score was 66% (lower, upper quartile 32, 83; range 0% to 100%). The number of diseased arteries (~70% diameter stenosis) correlated well with the extent score (r = 0.65, p
The smoothed curve of the relation between severity and extent score revealed a relatively straight initial portion, with an increase in slope at an extent of approxi-
ARTERY DISEASE/EXTENT AND SEVERITY OF CORONARY
DISEASE 517
the relation we have observed between severity and the extent of coronary atherosclerosis, which reflects the load of minor plaque. The precise nature of this relation has important implications in the assessment and management of patients with coronary artery disease. Our study indicates that when a single severe stenosis is present, approximately 40% of the length of the coronary tree is covered with atheroma. Thus, the so-called “solitary stenosis” in l-artery disease may be a misnomer, since overall coronary artery disease may already be moderately extensive. In several statistical models, the relation between extent and severity is not a simple straight line; instead, the slope of the relation increases markedly when there are 2 to 3 severe stenoses. This could explain the observed differences in prognosis between l-, 2-, and 3-artery disease in previous studies. In the studies of Bruschke, ‘,* Thompson, 5 and their co-workers, there was a much larger difference in DISCUSSION prognosis between l- and 2-artery disease than beThe results of this study show that traditionally obtained scores of severity, such as the number of tween 2- and 3-artery disease. Our study indicates arteries with ~70% stenosis, are strongly related to that as the severity progresses from l- to 2-artery the extent of coronary atherosclerosis. The wide- disease, the extent of coronary atheroma increases spread use of severity scores for coronary disease is from 40% to 75% of the coronary tree; after this, the understandable given the utility and prognostic in- extent of coronary disease increases only slightly, formation of angiography for defining the number of even when multiple severe stenoses are present. We relied on visual angiographic assessmentfor significant obstructive stenoses.‘I* Recent angiographic, angioscopic, and pathologic studies, how- both the severity and extent of coronary atheroscleever, have shown that the major events in coronary rosis, which may lack accuracy. However, we have disease-sudden cardiac death, myocardial infarc- previously reported a relatively low measurement ertion, and unstable angina pectoris-are caused by ror and good reproducibility between observers.” rupture of relatively minor plaques.6-9S16-22 The num- We did not assessall of the small coronary branches ber and extent of such minor stenoses are better de- for extent of atherosclerosis, so the score does not scribed by a score of the extent of atherosclerosis take into account the whole coronary tree. Our extent that takes into account all plaques, rather than by a score has not been validated against other techniques score of severe stenoses only. The same studies have such as intravascular ultrasound, which has been shown that occlusion at the site of a severe stenosis shown to be more accurate than standard angiograis usually silent. 6*8,9 For this reason, it may seem sur- phy in detecting minor plaque. The use of intravasprising that severity scores do convey important cular ultrasound to determine the total extent of corprognostic information. The likely reason for this is onary atherosclerosis is not practicable, however, as mately 80%. The fitted 2-phase model (2 intersecting straight lines; Figure 2) defined the relation better than a straight line ( Fl,lzl = 6.9, p = 0.001 ), in keeping with the pattern suggested by the smoothed curve. The intersection point of the 2 lines was an extent score of 87% (95% confidence interval, 67% to 96% extent). This model predicts that if there is 1 severe stenosis, then 41% (on average) of the coronary tree will actually be involved by angiographically evident plaque (Figure 2). The much steeper slope of the relation when there are 2 to 3 stenoses suggests that such patients usually have very extensive coronary atherosclerosis. The relation between the severity score and extent score also could be described by an exponential function (r = 0.67, p
lo-
FIGURE2. Scatterplot of the relation behmen severi score and extent score. This re7ation is well described by 2 intersecting straight lines, with a steeper increase in disease severity when the extent score is between 80%. and 90% (FIJ1zl= 6.9, p = 0.001). The intersection point of the 2 lines is an extent score of 87% (95% confidence interval 67% to 96% extent).
. 0
FTmACOROE
80
100
(%) 518
THE AMERICAN JOURNAL OF CARDIOLOGY@
VOL. 78
SEPTEMBER 1, 1996
it would require a full interrogation of the entire coronary tree with an ultrasound catheter. Although our findings on the extent of atherosclerosis based on angiography have not been validated by postmortem analysis, they are consistent with reported pathologic findings, that >50% of the coronary tree is usually covered by raised atheroma before a clinical event has occurred.‘6-20 In future prospective studies, it may be important to determine whether the extent of coronary atherosclerosis carries greater prognostic information than severity scores, because of the apparent importance of the load of minor versus obstructive atheromatous plaque.
7. Ambrose JA, Winters SL, Arora RR, Eng A, Riccio A, Gorlin R, Fuster V. Angiographic evolution of coronary artery morphology in unstable angina. J Am Co11 Cardiol 1986;7:472-478.
8. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Cdl Cardiol 1988;12:56-62. 9. TaeymansY, Theruox P, LesperanceJ, Waters D. Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion. Circulation 1992.8578-85. 10. Brown BG, Zhao X-Q, Sacco DE, Alberts JJ. Lipid lowering and plaque regression.New insights into prevention of plaque disruption andclinical events in coronary disease.Circulation 1993;87:1781- 1791. I 1. Sullivan DR, Matwick TH, Freedman SB. A new method of scoring coronary angiogramsto reflect extent of coronary atherosclerosisand improve correlation with major risk factors. Am Hem J 1990;119:1262-1267. 12. Austen WG, Edwards JE, Frye RL, Gemini GG, Gott VL, Griffith LSC, McGoon DC, Murphy ML, Roe BB (b). AHA Committee Report: a report system on patients evaluated for coronary disease,Council on Cardiovascular Surgery, American Heart Association. Circulation 1975;51(suppl):7-40. 13. Gebski V, Leung 0, McNeil D, Lunn D. SPIDA User’s Manual (Version 61 1992. Eastwood. New South Wales. Australia: Statistical Comoanv Labor;tory Pty. Ltd., 1992. 14. Cleveland WS. Robust locally-weighted regression and smoothing scatterplots. Am J Stat Assoc 1979;74:829-836. 15. Hastie TJ, Tibshiian RJ. Generalized Additive Models. London: Chapman and Hall, 1990. 16. Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease.Circuhtion 1990;86(suppl II):II-38-11-46. 17. Davies MJ, Thomas AC. Plaque fissuring-the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985;53:363-373. 18. Falk E. Why do plaques rupture? Circulation 1992;86(suppl III):III-30.
1. Bruschke AVG, Proudfit WL, Sones FM Jr. Progressive study of 590 consecutive nonsurgical casesof coronary diseasefollowed 5-9 years: I. Angiographic correlations. Circularion 1973;47:1147-1153. 2. Bruscbke AVG. Kramer JR, Bal ET, Haque IU, Detrano RC, Goormastic M. The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J 1989;117:296-305, 3. The CASS Principal Investigators and Their Associates. A randomized trial of coronary artery bypasssurgery. Survival data. Circulahm 1983;68:939-950. 4. Proudfit WJ, Bruschke AVG, MacMillan JP, Williams GW, Sones FM Jr. Fifteen-year survival study of patients with obstructive corouary artery disease. Circulation 1983;68:986-997. 5. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW, for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995;332:635-641. 6. Little WC, ContantinescuM, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, SantamoreWP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulafion 1988;78:1157-l 166.
I
111-42.
19. Davies MJ, Thomas AC. Thrombosis and acute coronary-artery lesions in suddencardiac ischemic death. N Engl J Med 1984;3 10:1137- 1140. 20. Solberg LA, Strong JP.Risk factors and atherosclerosis:a review of autopsy studies.Arteriosclerosis 1983;3:187- 198. 21. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or death. Autopsy evidence of recurrent mural tbrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985;71:699-708. 22. Mizuno K, Miyamoto A, SatomuraK, Kurita A, Arai T, SakuradaM, Yatagida S, N&mum H. Angioscopic coronary macromorphology in patients with acute coronary disorders. Lancer 1991;337:809-811.
CORONARY ARTERYDISEASE/EXTENTAND SEVERITYOF CORONARY DISEASE 519
MD, David S. Celermaier,
MB, BS, PhD, Thomas Lumley, MSC,
and S. Ben Freedman, MB, BS, PhD Most acute coronary events occur because of narrowings at sites of angiographically minor plaque. Despite this, angiogmms are reported in terms of the number of coronary arteries with severe narrowings. Disease severity is correlated with prognosis, but this may simply be due to a strong positive correlation between the severity and extent of coronary atheroma. We therefore aimed to assess the relation between the severity and the extent of coronary atherosclerosis. Coronary angiograms of 350 consecutive patients referred for elective cardiac catheterization were analyzed. Two independent observers calculated the number of arteries with ~70% stenosis, a disease severity score, and an extent score (percentage of the coronary artery length with any luminal irregularity). There were no obstructive &noses in 123 patients (35%); 91 (26%) had 1-vessel disease,
81 (23%) had 2-vessel disease, and 55 (16%) had 3vessel coronary artery disease. The median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8), and the median extent score was 66% (lower, upper quartile 32,83; range 0% to 100%). There was a strong linear relation between severity score and extent score (r = 0.62, p
orbidity and mortality in patients with coronary artery disease are related to the number M of major epicardial arteries with 250% or 270%
were scored for extent and severity of coronary artery disease, as detailed later. The indications for cardiac catheterization were stable angina pectoris in diameter reduction. l-5 The method of scoring coro- 146 (42%)) unstable angina in 94 (27%)) prognostic nary angiograms for the number of arteries showing reasons following myocardial infarction in 32 (9%)) coronary stenoses has been widely accepted, in part assessment of valvular disease in 32 (9%)) atypical because of the prognostic value of this score. Despite chest pain in 22 (6%)) and other reasons in 24 (7%). this, acute coronary events are usually due to arterial Patients were excluded if they had a history of corocclusion or thrombotic complication at sites of pre- onary artery surgery or coronary angioplasty. viously minor disease.6-g In patients who have had Coronary angiogmphy: Coronary angiography was coronary angiograms performed on 2 occasions, total performed by the standard Judkins or Sones techocclusion of a previously severe stenosis is likely to nique and was recorded on 35 mm tine films or digbe clinically silent, whereas unstable angina or acute ital/analog laser disc. Coronary angiograms were inmyocardial infarction is more likely to have resulted terpreted visually using multiple orthogonal views. from progression of a relatively minor plaque.6-g Coronary scores: Coronary angiograms were Major clinical coronary events may therefore be re- scored by 3 techniques. lated better to the extent of minor plaque in the corNUMBER OF DISEASED ARTERIES: This score onary arteries than to the number of obstructive le- counted the number of coronary arteries (left antesions.” In this study, we estimated the extent of rior descending artery, left right circumflex and arcoronary atherosclerosis using a novel extent score tery) with 270% diameter stenosis (i.e., scores rang(percent of the coronary tree covered by any irreg- ing from 0 to 3). Left main stenosis 250% was ularity) l1 and explored the relation between this ex- scored as l-vessel disease. tent score and more traditional measures of coronary SEVERITY SCORE: In this score, a value of 1 was artery disease severity. given to any of 15 arterial segments (as defined by the American Heart Association)” that contained METHODS 270% diameter stenosis, giving a potential score Subiectsz Coronary angiograms of 350 consecutive patients referred for elective coronary angiography range from 0 to 15. This score therefore gives a more complete measure of disease severity than simply the number of major arteries involved. From the Department of Cardiology, Royal Prince Alfred Hospital, Camoerdown. Svdnev; and The NHMRC Clinical Trials Centre. UniEXTENT SCORE:We developed this score previversi$ of Sydney: Sydhey, Australia. Manuscript received November ously to estimate the percentage of the coronary ar17. 1995: revised manuscriot received and acceoted Aoril 1 1996. tery length involved by atheroma.” Briefly, the pro‘Addrek for reprints: Pkfessor S. B. FreedAan, depariment of portion of each vessel involved by any atheroma, Cardiology, Concord Hospital, Hospital Road, Concord, Sydney, identified by luminal irregularity, was multiplied by NSW, 2 139, Australia. 5
16
0 1996 by Excerpta Medico, All rights reserved.
Inc
0002-9 149/96/$15.00 PII SOOO2-9149(96)00355-4
r=O.GS y
I
0
20
40
Extelrt
80
60
100
Score (%I
FIGURE 1. Relation between he number of diseased arteries with 270% stenosis and extent score. The data poink represent mean + 2 SEM (95% confidence intervals).
in an approximately linear fashion. This linear relation was then used to estimate the SD as a function of disease extent for each measurement. The reciprocal of the variance (the precision) was then used as a weight for each observation in the weighted analyses. A scatterplot smoother I4 was then applied to these data. This gives an estimate of the relation between the 2 variables without making assumptions about the form of a model. The curve was relatively straight up to about 80% disease extent and then rose more sharply for more extensive disease. A formal test of this behavior was carried out by constructing a 2-phase regression curve, in which the relation is assumed to be linear but with a change in slope at some unspecified point. This intersection point was chosen by minimizing the weighted residual sum of squares from the fitted 2-phase regression model. A 95% confidence interval was calculated using an F test.15
RESULTS a factor for each vessel: left main artery, 5; left anterior descending artery, 20; main diagonal branch (or branches), 10; first septal perforator, 5; left circumflex artery, 20; obtuse marginal artery and posterolateral branch together, 10; right coronary artery, 20; and main posterior descending branch, 10. When the major lateral wall branch was a large obtuse marginal or intermediate vessel with no posterolateral branches, these were given a factor of 20, and the left circumflex artery a factor of 10. When a vessel was occluded and the distal vessel was not fully visualized by coronary collateral flow, the proportion of the vessel not visualized was given the mean score of the remaining arteries. The scores for each vessel or branch were added to give a total score out of 100. The number of arteries and severity scores were based on the consensus opinion of 2 experienced angiographers. The extent score was obtained independently by a third angiographer. The interobserver error of extent score (mean unsigned difference between 2 estimates + SD) has been reported previously to be 5 + 4% in our laboratory.” In this series, a second blinded extent score was measured by the same observer 1 month after the first reading in 40 randomly selected cases; the intraobserver error was 2 + 2%. Statistical analysis: Data were analyzed using the Statistical Programme for Interactive Data Analysis (SPIDA) .I3 All descriptive data are expressed as mean 5 SD. In the variability studies, inter- and intraobserver variabilities were expressed as the mean of the unsigned differences between paired readings 2 SD of the mean difference. Standard linear regression was used to assessthe relation between the number of arteries with ~70% stenosis and extent score. For comparison of the severity score with the extent score, the data were divided into 5 groups according to extent score (0 to 20%, 21 to40%, 41 to 60%, 61 to 80%, 81 to lOO%), and the SD of the severity score was calculated for each group. These SDS increased with disease extent CORONARY
Subjects: There were 249 men (71%) and 101 women (29%) (mean age 60 ? 10 years [range 30 to 851). One hundred nineteen (34%) had never smoked cigarettes, 32 (9%) were current smokers, and 199 (57%) were former smokers. The average lifetime smoking was 22 ? 10 pack-years (range 2 to 140). There were 45 patients (13%) with diabetes mellitus (all had type 2 or noninsulin-dependent diabetes), and 118 (34%) had a history of systemic hypertension. One hundred subjects (29%) had a family history of premature vascular disease. In total, 152 subjects (43%) gave a history of hypercholesterolemia, although only 48 ( 14%) were taking lipidlowering drugs. Angiographic results: One hundred twenty-three patients (35%) had no arteries with 270% stenosis; 91 (26%) had l-artery, 81 (23%) had 2-artery, and 55 ( 16%) had 3-artery coronary disease. The median number of diseased arteries was 1 (lower, upper quartile 0,2; range 0 to 3 ) , the median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8)) and the median extent score was 66% (lower, upper quartile 32, 83; range 0% to 100%). The number of diseased arteries (~70% diameter stenosis) correlated well with the extent score (r = 0.65, p
The smoothed curve of the relation between severity and extent score revealed a relatively straight initial portion, with an increase in slope at an extent of approxi-
ARTERY DISEASE/EXTENT AND SEVERITY OF CORONARY
DISEASE 517
the relation we have observed between severity and the extent of coronary atherosclerosis, which reflects the load of minor plaque. The precise nature of this relation has important implications in the assessment and management of patients with coronary artery disease. Our study indicates that when a single severe stenosis is present, approximately 40% of the length of the coronary tree is covered with atheroma. Thus, the so-called “solitary stenosis” in l-artery disease may be a misnomer, since overall coronary artery disease may already be moderately extensive. In several statistical models, the relation between extent and severity is not a simple straight line; instead, the slope of the relation increases markedly when there are 2 to 3 severe stenoses. This could explain the observed differences in prognosis between l-, 2-, and 3-artery disease in previous studies. In the studies of Bruschke, ‘,* Thompson, 5 and their co-workers, there was a much larger difference in DISCUSSION prognosis between l- and 2-artery disease than beThe results of this study show that traditionally obtained scores of severity, such as the number of tween 2- and 3-artery disease. Our study indicates arteries with ~70% stenosis, are strongly related to that as the severity progresses from l- to 2-artery the extent of coronary atherosclerosis. The wide- disease, the extent of coronary atheroma increases spread use of severity scores for coronary disease is from 40% to 75% of the coronary tree; after this, the understandable given the utility and prognostic in- extent of coronary disease increases only slightly, formation of angiography for defining the number of even when multiple severe stenoses are present. We relied on visual angiographic assessmentfor significant obstructive stenoses.‘I* Recent angiographic, angioscopic, and pathologic studies, how- both the severity and extent of coronary atheroscleever, have shown that the major events in coronary rosis, which may lack accuracy. However, we have disease-sudden cardiac death, myocardial infarc- previously reported a relatively low measurement ertion, and unstable angina pectoris-are caused by ror and good reproducibility between observers.” rupture of relatively minor plaques.6-9S16-22 The num- We did not assessall of the small coronary branches ber and extent of such minor stenoses are better de- for extent of atherosclerosis, so the score does not scribed by a score of the extent of atherosclerosis take into account the whole coronary tree. Our extent that takes into account all plaques, rather than by a score has not been validated against other techniques score of severe stenoses only. The same studies have such as intravascular ultrasound, which has been shown that occlusion at the site of a severe stenosis shown to be more accurate than standard angiograis usually silent. 6*8,9 For this reason, it may seem sur- phy in detecting minor plaque. The use of intravasprising that severity scores do convey important cular ultrasound to determine the total extent of corprognostic information. The likely reason for this is onary atherosclerosis is not practicable, however, as mately 80%. The fitted 2-phase model (2 intersecting straight lines; Figure 2) defined the relation better than a straight line ( Fl,lzl = 6.9, p = 0.001 ), in keeping with the pattern suggested by the smoothed curve. The intersection point of the 2 lines was an extent score of 87% (95% confidence interval, 67% to 96% extent). This model predicts that if there is 1 severe stenosis, then 41% (on average) of the coronary tree will actually be involved by angiographically evident plaque (Figure 2). The much steeper slope of the relation when there are 2 to 3 stenoses suggests that such patients usually have very extensive coronary atherosclerosis. The relation between the severity score and extent score also could be described by an exponential function (r = 0.67, p
lo-
FIGURE2. Scatterplot of the relation behmen severi score and extent score. This re7ation is well described by 2 intersecting straight lines, with a steeper increase in disease severity when the extent score is between 80%. and 90% (FIJ1zl= 6.9, p = 0.001). The intersection point of the 2 lines is an extent score of 87% (95% confidence interval 67% to 96% extent).
. 0
FTmACOROE
80
100
(%) 518
THE AMERICAN JOURNAL OF CARDIOLOGY@
VOL. 78
SEPTEMBER 1, 1996
it would require a full interrogation of the entire coronary tree with an ultrasound catheter. Although our findings on the extent of atherosclerosis based on angiography have not been validated by postmortem analysis, they are consistent with reported pathologic findings, that >50% of the coronary tree is usually covered by raised atheroma before a clinical event has occurred.‘6-20 In future prospective studies, it may be important to determine whether the extent of coronary atherosclerosis carries greater prognostic information than severity scores, because of the apparent importance of the load of minor versus obstructive atheromatous plaque.
7. Ambrose JA, Winters SL, Arora RR, Eng A, Riccio A, Gorlin R, Fuster V. Angiographic evolution of coronary artery morphology in unstable angina. J Am Co11 Cardiol 1986;7:472-478.
8. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Cdl Cardiol 1988;12:56-62. 9. TaeymansY, Theruox P, LesperanceJ, Waters D. Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion. Circulation 1992.8578-85. 10. Brown BG, Zhao X-Q, Sacco DE, Alberts JJ. Lipid lowering and plaque regression.New insights into prevention of plaque disruption andclinical events in coronary disease.Circulation 1993;87:1781- 1791. I 1. Sullivan DR, Matwick TH, Freedman SB. A new method of scoring coronary angiogramsto reflect extent of coronary atherosclerosisand improve correlation with major risk factors. Am Hem J 1990;119:1262-1267. 12. Austen WG, Edwards JE, Frye RL, Gemini GG, Gott VL, Griffith LSC, McGoon DC, Murphy ML, Roe BB (b). AHA Committee Report: a report system on patients evaluated for coronary disease,Council on Cardiovascular Surgery, American Heart Association. Circulation 1975;51(suppl):7-40. 13. Gebski V, Leung 0, McNeil D, Lunn D. SPIDA User’s Manual (Version 61 1992. Eastwood. New South Wales. Australia: Statistical Comoanv Labor;tory Pty. Ltd., 1992. 14. Cleveland WS. Robust locally-weighted regression and smoothing scatterplots. Am J Stat Assoc 1979;74:829-836. 15. Hastie TJ, Tibshiian RJ. Generalized Additive Models. London: Chapman and Hall, 1990. 16. Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease.Circuhtion 1990;86(suppl II):II-38-11-46. 17. Davies MJ, Thomas AC. Plaque fissuring-the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985;53:363-373. 18. Falk E. Why do plaques rupture? Circulation 1992;86(suppl III):III-30.
1. Bruschke AVG, Proudfit WL, Sones FM Jr. Progressive study of 590 consecutive nonsurgical casesof coronary diseasefollowed 5-9 years: I. Angiographic correlations. Circularion 1973;47:1147-1153. 2. Bruscbke AVG. Kramer JR, Bal ET, Haque IU, Detrano RC, Goormastic M. The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J 1989;117:296-305, 3. The CASS Principal Investigators and Their Associates. A randomized trial of coronary artery bypasssurgery. Survival data. Circulahm 1983;68:939-950. 4. Proudfit WJ, Bruschke AVG, MacMillan JP, Williams GW, Sones FM Jr. Fifteen-year survival study of patients with obstructive corouary artery disease. Circulation 1983;68:986-997. 5. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW, for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995;332:635-641. 6. Little WC, ContantinescuM, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, SantamoreWP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulafion 1988;78:1157-l 166.
I
111-42.
19. Davies MJ, Thomas AC. Thrombosis and acute coronary-artery lesions in suddencardiac ischemic death. N Engl J Med 1984;3 10:1137- 1140. 20. Solberg LA, Strong JP.Risk factors and atherosclerosis:a review of autopsy studies.Arteriosclerosis 1983;3:187- 198. 21. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or death. Autopsy evidence of recurrent mural tbrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985;71:699-708. 22. Mizuno K, Miyamoto A, SatomuraK, Kurita A, Arai T, SakuradaM, Yatagida S, N&mum H. Angioscopic coronary macromorphology in patients with acute coronary disorders. Lancer 1991;337:809-811.
CORONARY ARTERYDISEASE/EXTENTAND SEVERITYOF CORONARY DISEASE 519