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(Chest. 2001;120:1525-1533.)
© 2001 American College of Chest Physicians

Differential Coronary Calcification on Electron-Beam CT Between Syndrome X and Coronary Artery Disease in Patients With Chronic Stable Angina Pectoris*

Lung-Ching Chen, MD; Jaw-Wen Chen, MD; Mei-Han Wu, MD; Ju-Chi Liu, MD; Gong-Yau Lan, MD; Philip Yu-An Ding, MD, PhD and Mau-Song Chang, MD

* From the Division of Cardiology (Drs. L-C Chen, J-W Chen, Ding, and Chang), Department of Medicine, Taipei Veterans General Hospital and Cardiovascular Research Center, National Yang-Ming University School of Medicine; Department of Radiology (Dr. Wu), Taipei Veterans General Hospital; Division of Cardiovascular Medicine (Dr. Liu), Taipei Medical University and affiliated Taipei Wan Fang Hospital; and Department of Medical Imaging (Dr. Lan), Cheng-Hsin General Hospital, Taipei, Taiwan, Republic of China.

Correspondence to: Jaw-Wen Chen, MD, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Rd, Section 2, Taipei, Taiwan, 11217, Republic of China


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: The differential diagnosis of syndrome X and coronary artery disease (CAD) in patients with evidence of myocardial ischemia may be difficult. The possible difference in coronary calcium detected by electron-beam CT (EBCT) between syndrome X and CAD is rarely evaluated, especially in aged patients with chronic, stable angina.

Design and settings: Prospective, controlled study at a tertiary referral medical center.

Patients and measurements: Forty patients with syndrome X (85% male) and 53 patients with CAD (89% male) were enrolled. Ten control subjects (90% male) with negative exercise treadmill test results and normal coronary angiographic findings served as control subjects. EBCT determined the coronary calcium scores (CCSs), and standard cardiovascular risk factors of all study subjects were analyzed.

Results: The 93 study patients had CCSs that ranged from 0 to 1,857. Coronary calcification was seen in 2 of the 10 control subjects (20%), 21 of the 40 syndrome X patients (52.5%), and 51 of the 53 CAD patients (96.2%) [p < 0.01]. The CCS (median [range]) was significantly lower in syndrome X patients than in CAD patients: 1 (0 to 117) vs 202 (0 to 1,857) [p < 0.001]. Receiver operating characteristic curve analyses also demonstrated that coronary calcification differentiated syndrome X from CAD (area under curve, 0.891; 95% confidence interval, 0.806 to 0.947). Of the CAD patients whose CCSs were < 117 and overlapped with CCSs of syndrome X, multivariate analyses determined CCS > 5 (odds ratio, 13.1; 95% confidence interval, 2.86 to 59.7), hypertension (odds ratio, 6.4; 95% confidence interval, 1.5 to 27.4), and hypercholesterolemia (odds ratio, 6.7; 95% confidence interval, 1.5 to 30.5) to be independent discriminators to differentiate CAD from syndrome X. Patients with CAD had more frequent hypertension than patients with syndrome X.

Conclusions: The coronary calcium detected noninvasively by EBCT was different, though with some overlapping, between patients with syndrome X and CAD. In addition to standard cardiovascular risk factors, CCS determined by EBCT (especially > 117 or = 0) could differentiate between syndrome X and CAD in patients with chronic, stable angina with evidence of myocardial ischemia. Larger trials would be useful to validate CCS on EBCT as a predictor of clinical outcome in these patients.

Key Words: coronary artery disease • coronary calcification • electron-beam CT • syndrome X


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The term syndrome X, first raised by Kemp et al1 in 1973 to describe a group of patients with typical angina and normal coronary angiographic findings, is now widely used to specify patients with angina-like chest pain, ischemia-like ECG findings, normal coronary angiographic findings, and no evi

dence of epicardial coronary spasm. The pathophysiologic mechanisms that were suggested to be heterogeneous remain largely speculative in patients with syndrome X.2 3 Differential diagnosis of syndrome X and significant coronary artery disease (CAD) in patients with evident myocardial ischemia may sometimes be difficult clinically. None of the noninvasive diagnostic modalities, including the exercise treadmill test (ETT) or single-photon emission CT, can differentiate the two clinical conditions with high sensitivity and specificity.4 5 Because of limitations of the noninvasive tests, a substantial number of patients would finally undergo coronary angiography, which has been considered the "gold standard" of diagnosis. However, up to 30% of patients who underwent coronary angiography to evaluate the causes of chest pain may have angiographically normal coronary arteries.6

It has been suggested7 8 that the presence of coronary calcium is invariably associated with atherosclerosis, and electron-beam CT (EBCT) is a sensitive, accurate, quantitative and reproducible method to detect coronary artery calcium.9 10 11 12 13 To date, most EBCT studies11 14 showed good correlation between the total amount of coronary calcium and the degree of angiographically detected arterial obstruction. The utility of EBCT increased rapidly with growing evidence of its prognostic value in both symptomatic and asymptomatic patients.14 15 16 There are also reports on utilization of EBCT to compare the coronary calcium in stable angina pectoris and first myocardial infarction,17 to stratify patients presenting to the emergency department with chest pain,18 and in detection of atherosclerosis in women with syndrome X.19 However, the possible difference in coronary artery calcium between syndrome X and CAD patients has not been evaluated in aged men with chronic, stable angina, and the potential utility of EBCT in these patients has not been investigated to our knowledge. This study was then conducted to evaluate the coronary calcium scores (CCSs) in patients with chronic stable angina and evident myocardial ischemia, and to examine the possible usefulness of EBCT to differentiate syndrome X from CAD in these patients.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Population
A series of patients with chronic, stable angina pectoris who visited the cardiology clinics in a single tertiary medical center were initially evaluated. Patients with uncontrolled hypertension (systolic BP >= 180 mm Hg or diastolic BP >= 110 mm Hg), significant arrhythmia, left bundle-branch block, acute myocardial infarction, unstable angina, cardiomyopathy, significant valvular heart disease, congestive heart failure, uncontrolled diabetes mellitus (fasting plasma glucose > 200 µg/dL), collagen vascular disease, or history of previous coronary revascularization including balloon angioplasty, stenting, and coronary bypass surgery were excluded.

All patients were scheduled for ETT to evaluate the presence of myocardial ischemia. In patients with evident myocardial ischemia, coronary angiography was then performed to document the presence of angiographic stenosis. Patients were categorized to have CAD or syndrome X (angina-like chest pain, ischemia-like ECG findings, normal coronary angiographic results, and no evidence of epicardial coronary spasm) accordingly.20 A total of 93 patients with chronic, stable angina pectoris and ischemia-like ECG findings during exercise (including 40 consecutive syndrome X patients and 53 consecutive CAD patients) were enrolled. Their mean (± SD) age was 63.7 ± 9.8 years (range, 35 to 77 years), including 68 patients > 60 years old.

In addition, another 10 control subjects without clinical evidence of angina and myocardial ischemia were also included for comparison. We selected the control subjects with atypical chest discomfort or palpitation who underwent coronary angiography to exclude the possibility of CAD. Those subjects, mainly men from 50 to 70 years old, with negative ETT results and completely normal coronary angiographic findings, were included as control subjects and EBCT were performed. The study protocol was approved by the hospital human research committee, and written informed consent was obtained from each patient. The demographics and cardiovascular risk factors of the study patients, including hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg), diabetes mellitus (fasting plasma sugar > 126 mg/dL), hypercholesterolemia (fasting plasma total cholesterol > 240 mg/dL), and history of smoking, were also recorded.

ETT
Treatment with all antianginal medications except for sublingual nitroglycerine was withheld for at least 48 h before ETT. The modified Bruce protocol was used with the end point of chest tightness or fatigue. The result of the ETT was defined as positive when the ST segment, which was selected as 80 ms after the J point, was horizontally or downslopingly depressed >= 1 mm or upslopingly depressed >= 1.5 mm.20 21 22 Patients who did not achieve 90% of age-predicted heart rate, though without significant ST-segment depression, were defined as having inconclusive results and excluded from this study.

Coronary Angiography
Coronary angiography was performed in multiple oblique projections as mentioned in detail previously.23 Quantitative analyses were performed by three cardiologists (L.C.C., J.C.L., J.W.C.), who were blinded to the clinical and EBCT data. Measurements were made on end-diastolic frames with the use of digital electronic calipers from an optimally magnified image as mentioned previously.24 CAD was defined as significant if there was a >= 50% luminal diameter stenosis in any major epicardial coronary artery (left main, left anterior descending, circumflex, and right coronary artery) and insignificant if there was 20 to 50% luminal diameter stenosis in any major epicardial coronary artery. Patients with positive ETT findings but completely normal coronary angiographic findings received a diagnosis of syndrome X. Disagreements were resolved by a further joint reading.

EBCT Scanning and Image Analysis
Within 4 weeks before or after coronary angiography, EBCT scanning was performed in all study patients and control subjects using an Imatron C-150XP Ultrafast CT scanner (Imatron; South San Francisco, CA) and a standard thin-slice protocol with 3-mm image slices. Exposure time was 100 ms per image slice, and total skin radiation was < 6 mGy per scan. ECG triggering was used so that image acquisition occurred after 80% of the RR interval. Transverse image slices of the heart were obtained contiguously beginning 1 cm below the carina and progressed caudally. All EBCT scans were examined by two radiologists (M.H.W., G.Y.L.), who were blinded to all clinical and angiographic data, and were experienced in both angiographic anatomy and tomographic imaging. The area of each pixel was 0.34 mm2. A region of interest of 66 mm2 in area was created that is precisely centered on each focus of possible coronary calcification, defined as a volume of >= 8.16 mm3 with a CT number > 130 Hounsfield units (HU) within the distribution of a coronary artery. The mean and peak CT numbers and the area of the subsets of pixels with CT numbers > 130 HU within these regions were calculated. The CCS for the whole coronary tree was then calculated independently by both M.H.W. and G.Y.L., as follows: score = {Sigma} (area x n)(T/3), where area was the area (in square millimeters) of the region of interest with four or eight contiguous pixels with > 130 HU; n = 1 if 130 HU <= peak CT number <= 200 HU; n = 2 if 200 HU <= peak CT number <= 300 HU; n = 3 if 300 HU <= peak CT number <= 400 HU; and n = 4 if 400 HU <= peak CT number. T was the slice thickness. If the CCSs calculated by the two radiologists showed a difference of < 10 HU, the averages of the scores were obtained and used for further statistical analysis. If the CCSs calculated showed a difference > 10 HU, a joint reading was made to reach an agreement.

Statistical Analysis
Categorical variables were compared by Fisher’s Exact Test or {chi}2 test. Continuous variables with normal distribution were expressed as mean ± SD and compared by two-sample t tests. Because CCSs were not symmetrically distributed, they were presented as median (range) and compared by Kruskall-Wallis analysis of variance (ANOVA). The difference in CCSs between syndrome X and CAD patients was tested by Mann-Whitney ranked sum test. A p value < 0.05 was considered a statistically significant difference. Receiver operating characteristic (ROC) curves were constructed to determine the predictive value of CCSs to differentiate syndrome X and CAD. The ROC curves were constructed by calculating the sensitivity and specificity using different CCS threshold values (from 0 to 1,857) and plotting sensitivity vs 100 minus specificity. The data points were smoothed to fit a curve secondary to the small sample size. The definitions of various statistical terms used to describe the value and test characteristics are as follows: sensitivity, the probability that a test result will be positive when the disease is present; specificity, the probability that a test result will be negative when the disease is not present; positive likelihood ratio, the ratio between the probability of a positive test result given the presence of the disease and the probability of a positive test result given the absence of the disease; negative likelihood ratio, the ratio between the probability of a negative test result given the presence of the disease and the probability of a negative test result given the absence of the disease; positive predictive value, probability that the disease is present when the test result is positive; negative predictive value, probability that the disease is not present when the test result is negative; and accuracy, the proportion of all test results, both positive and negative, that are correct. Multivariate logistic regression was performed to test the standard cardiovascular risk factors and CCSs for independent discriminators of syndrome X and CAD. All statistical analyses were performed using the Statistical Package for Social Sciences software (SPSS 8.0 for Windows; SPSS; Chicago, IL) and MedCalc for Windows (version 4.2; MedCalc Software; Mariakerke, Belgium).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Patient Characteristics
The demographics and cardiovascular risk factors of all the study subjects are shown in Tables 1 , 2. The incidence of hypertension, disregarding age, was significantly lower in syndrome X patients as compared with CAD patients. When the patients were subclassified into ages <= 60 years and > 60 years, the incidence of hypertension was not statistically different in the latter group but still reached statistical significance in the former group (Table 2) . Other cardiovascular risk factors, including diabetes, hypercholesterolemia, and history of smoking, were not statistically different among the three groups of study subjects. Of the 53 patients with CAD, 10 patients had insignificant CAD, 22 patients had one-vessel disease (stenosis diameter of at least 50% in one coronary artery), 12 patients had two-vessel disease, and 9 patients had three-vessel disease.


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  		Table 1.. Demographic Data of Study Population*

 

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  		Table 2.. Demographic Data of Study Population by Age*

 
CCS
The CCSs for all study subjects ranged from 0 to 1,857. As shown in Table 3 , coronary calcification was seen in 2 of the 10 control subjects (20%), 21 of the 40 syndrome X patients (52.5%), and 51 of the 53 CAD patients (96.2%) [p < 0.01]. Only two patients with CAD had negative EBCT scan results (CCS = 0): one patient had maximum coronary stenosis of 40% in the left anterior descending artery, and the other patient had two-vessel disease (65% diameter stenosis at the proximal right coronary artery, and 60% diameter stenosis at first diagonal branch of the left anterior descending coronary artery). The CCS was statistically significantly lower in syndrome X patients as compared with CAD patients (p < 0.001). There was no difference in CCSs between syndrome X patients and control subjects.


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  		Table 3.. CCS in Study Population

 
The pattern of distribution of the CCSs in the three groups is shown in Figure 1 . The CCSs in the study population were also analyzed and compared between syndrome X and CAD patients by age (Table 4 ). The CCS (median [range]) was significantly lower in the syndrome X group as compared with CAD patients: 1 (0 to 117) vs 202 (0 to 1,857) [p < 0.001]. The difference between syndrome X and CAD was consistent in both age subgroups (<= 60 years and > 60 years). The pattern of distribution of CCSs in each subgroup is shown in Figure 2 . There were 24 CAD patients with CCSs in the range of 0 to 117 and overlapped with those of syndrome X. The cardiovascular risk factors and CCSs of these patients were entered into a subgroup analysis.



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  		Figure 1.. The pattern of distribution of the CCS in syndrome X (SX), CAD, and control subjects. The dotted line indicates the median value in each group. NS = not significant.

 

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  		Table 4.. CCS in Study Population by Age

 


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  		Figure 2.. The pattern of distribution of the CCS in subgroups of syndrome X, CAD, and control subjects. The dotted line indicates the median value in each group. See Figure 1 for expansion of abbreviation.

 
ROC Curve Analysis for CCS
We constructed the ROC curves for CCS in the whole study population, and in both age <= 60 years and age > 60 years subgroups (Fig 3 ). Each data point corresponds to the sensitivity and specificity of a particular CCS for the specified definition of disease. An area under the ROC curve of 0.5 would imply equity between true-positive and false-positive test results. Curve areas > 0.5 represent tests with increasingly greater diagnostic accuracy up to the "perfect" test (100% sensitive, 100% specific) at a curve area of 1.0. The areas under ROC curves are shown in Table 5 , all demonstrating the ability of CCS to differentiate syndrome X and CAD. As shown in Table 6 , for the whole patient group, CCSs <= 5 differentiated syndrome X from CAD best, with sensitivity of 75%, specificity of 91%, positive predictive value of 86%, negative predictive value of 83%, and accuracy of 84%. The positive likelihood ratio and negative likelihood ratio are 3.9 and 0.2, respectively. For patients <= 60 years old, CCS = 0 differentiated syndrome X from CAD best, with sensitivity of 80%, specificity of 90%, positive predictive value of 92%, negative predictive value of 75%, and accuracy of 84%. The positive likelihood ratio and negative likelihood ratio are 8.0 and 0.2, respectively. For patients > 60 years old, CCSs <= 45 differentiated syndrome X from CAD best, with sensitivity of 92%, specificity of 77%, positive predictive value of 70%, negative predictive value of 94%, and accuracy of 82%. The positive likelihood ratio and negative likelihood ratio are 3.9 and 0.1, respectively.



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  		Figure 3.. ROC curves for CCS in both age <= 60 years and age > 60 years subgroups. Areas under the curve, representing the ability to differentiate syndrome X from CAD, are 0.873 and 0.909 for subgroup of age <= 60 years old and > 60 years old, respectively.

 

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  		Table 5.. Areas Under ROC Curves to Differentiate Syndrome X and CAD

 

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  		Table 6.. CCS to Differentiate Syndrome X From CAD*

 
Subgroup Analysis of CAD Patients With CCSs < 117 and Multivariate Logistic Regression Analysis
Because there were 24 CAD patients with CCSs < 117 and overlapped with the CCSs of syndrome X patients, we further analyzed the cardiovascular risk factors, angiographic extent of coronary disease, and CCSs of these patients and compared them with those of syndrome X. The incidence of hypertension and hypercholesterolemia was higher in CAD than in syndrome X in this subgroup of patients. Most of the CAD patients (87.5%) with a CCS < 117 had insignificant or one-vessel disease, only 8.3% of them had two-vessel disease, and 4.2% had three-vessel disease (Table 7 ). The cardiovascular risk factors and CCSs were then entered into a multivariate logistic regression analysis to determine the independent discriminators of syndrome X and CAD. Hypertension, hypercholesterolemia, and CCS > 5 were independent discriminators of syndrome X and CAD. The odds ratios of these three factors are shown in Table 8 . Therefore, for patients with a CCS < 117, the concomitant presence of hypertension and/or hypercholesterolemia would increase the likelihood of CAD.


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  		Table 7.. Subgroup Analysis of 64 Patients With Anginal Chest Pain and Ischemic ECG Findings During ETT With CCS < 117*

 

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  		Table 8.. Odds Ratio of CAD as Compared With Syndrome X in Patients With Anginal Chest Pain and Ischemic ECG Findings During ETT With CCS < 117

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The purpose of this study was to evaluate whether CCS determined noninvasively by EBCT could differentiate syndrome X from CAD in patients with chronic, stable angina and exercise-induced myocardial ischemia. Differentiation of syndrome X from CAD has both therapeutic and prognostic implications. Syndrome X comprises a heterogeneous group of patients with clinical presentation of anginal chest pain, ischemia-like ECG findings, and normal coronary angiographic results. It is generally considered to be a relatively benign clinical entity associated with a good prognosis, and only limited treatment is necessary.25 26 However, patients with angiographic evidence of CAD require aggressive lifestyle modifications, appropriate and adequate medical therapy, and even revascularization procedures if indicated.

Our results showed that the CCSs of syndrome X and CAD patients were different, and the difference was large enough for EBCT to differentiate the two groups with high sensitivity, specificity, and accuracy. None of the syndrome X patients had a CCS > 117. Thus, a CCS > 117 might be used as a reference indicator of CAD in patients with chronic stable angina and positive ETT results. However, 24 of the 54 CAD patients (45%) had relatively low CCSs that overlapped with the CCSs of the syndrome X patients. In these CAD patients, the incidence of hypertension and/or hypercholesterolemia was statistically significantly higher than in patients with syndrome X. Nevertheless, compared to other traditional coronary risk factors such as hypercholesterolemia and hypertension, the CCS was still the most powerful discriminator between CAD and syndrome X in patients with anginal chest pain, clinical myocardial ischemia, and a relatively low CCS (< 117) on EBCT. This finding was in concordance with a previous study27 showing that EBCT scanning offers improved discrimination over conventional risk factors in the identification of persons with angiographically confirmed coronary disease. For patients with a low (< 117) CCS, status of conventional cardiovascular risk factors such as hypertension and hypercholesterolemia should also be accounted to better differentiate between patients with CAD and syndrome X. The logical next step to these patients would be to consider a thallium stress testing or go directly for coronary angiography. While this approach seems not much different from that of traditional approach, there are, however, a number of very significant differences. First, for patients with a CCS outside this "gray zone" (CCS > 117 or = 0), the decision making would be straightforward. These patients may not need stress testing to stratify their risks, and the medical cost in managing these patients might be reduced. Second, EBCT is an anatomic evaluation for atherosclerotic plaque and its severity; it is not a physiologic test for inducible ischemia. The measure of disease severity by EBCT does not depend on exercise ability, it does not depend on whether there is a normal or abnormal resting ECG finding, and it does not depend on whether the patient is receiving any cardiac medications that might interfere with interpretation.28 It is not known why patients with syndrome X had less coronary calcification than that in CAD patients. One of the possibilities is that, as shown in the present study, a coronary risk factor such as hypertension is more frequently seen in the latter group. However, the low CCS in syndrome X patients was comparable to those of control subjects, suggesting that the epicardial coronary artery was less injured, while myocardial ischemia is probably related to so-called "microvascular dysfunction" in the former group.23 29

Previous fluoroscopic, pathologic, and EBCT study30 have shown that the prevalence and extent of coronary artery calcium increased with age in both men and women, even when no significant coronary stenosis was present.30 In the present study, the discriminating values of CCSs for syndrome X and CAD patients at different age groups were carefully evaluated and showed consistent results. The accuracy of EBCT to predict the presence of significant CAD found in this study is 82.3% and 84%, respectively, in either age group, which was at least as good as most thallium exercise test results reported before.31 More importantly, the EBCT procedure is easy to perform and safe, and the result of EBCT is relatively objective and not dependent on patients’ exercise performance. Thus, in patients with chronic, stable angina who are hesitating and/or are unable to undergo coronary angiography, EBCT could be one of the choices to evaluate the possible presence of significant CAD. However, compared to that in CAD patients, the CCS was significantly lower in normal subjects with negative ETT results and in patients with positive ETT results but no CAD (syndrome X). EBCT might also be helpful to evaluate the possible presence of angiographically significant stenosis in major coronary arteries in patients who cannot tolerate exercise and/or have inconclusive results of ETT due to insufficient efforts.

There are some limitations in this study. Firstly, intravascular ultrasound was not performed. In addition to giving morphologic information on the vessel wall and lumen size, intravascular ultrasound may also quantify atheromatous plaque morphology and plaque composition. It offers distinct advantages over coronary angiography for the detection of atherosclerosis, especially in the early stages. However, in daily practice, coronary angiography but not intravascular ultrasound is used as the "gold standard" for diagnosis of CAD.32 It is evident that patients with normal coronary angiographic findings but significant exercise-induced myocardial ischemia have a favorable long-term prognosis, much better than patients with documented CAD by coronary angiography.33 Although we cannot exclude the possibility that some of our patients with syndrome X may have minor plaque on intravascular ultrasound, according to a previous large-scale study, it is very likely that such patients may have a good long-term prognosis compared with CAD patients with evident coronary stenosis documented by coronary angiography. Thus, the differentiation between syndrome X and CAD by CCSs determined by EBCT has important clinical implication. As reported by others,34 35 the epicardial coronary artery is rarely completely normal in patients with syndrome X. The study done by Wiedermann et al35 showed that most patients with syndrome X had abnormal coronary arteries by intravascular ultrasound. Intravascular ultrasound identified three distinct morphologic groups: normal coronary arteries, atheromatous plaque, and intimal thickening. In the present study, three of the patients in the syndrome X group had CCSs > 50 (71, 94, and 117, respectively), suggesting that a normal coronary angiographic finding might not indicate a normal coronary artery. Shemesh et al19 also found that the prevalence of coronary calcium in a group of syndrome X women was 63%, which could be due to the fact that an angiogram is essentially a luminogram and atherosclerotic changes within the arterial wall are underestimated. Furthermore, the lumen diameter may not be affected, because plaque formation is accompanied by compensatory enlargement of the vessel (vessel remodeling). With EBCT, these lesions can be diagnosed more easily and the appropriate antiatherosclerotic treatment can be started early. Secondly, there is no one-to-one relationship between coronary calcification and angiographic stenosis,36 where patients with significant angiographic stenosis may have only mild coronary calcification, especially in those with lipid-rich unstable plaque observed on angioscopy and intravascular ultrasound. Thus, the implication of the results from the present study should be limited to patients with chronic, stable angina who are in relatively stable clinical condition and with minimal previous coronary intervention. Finally, this is a single-center experience involving patients, mainly male, with moderate-to-high cardiovascular risk. The conclusion drawn from the present study should be used in another patient population cautiously. Though the cutoff value of CCS determined from this study may be used in conjunction with clinical variables to assess patients with chronic, stable angina, further evaluation should be done to confirm its reliability in another larger group of patients suspected of having CAD.

In conclusion, the coronary calcium detected noninvasively by EBCT was different, though with some overlapping, between patients with syndrome X and CAD. In addition to standard cardiovascular risk factors, CCS determined by EBCT (especially > 117 or = 0) could help differentiate between syndrome X and CAD in patients with chronic, stable angina. It is important clinically because the long-term prognosis of syndrome X and CAD is quite different. Though coronary calcium may not accurately predict near-term future coronary events in asymptomatic, high-coronary-risk subjects, as suggested by Detrano et al,37 we did show that CCSs on EBCT could help to identify syndrome X, a disease with good long-term prognosis, noninvasively in symptomatic patients with evidence of myocardial ischemia. Further large-scale study would be useful to validate CCSs on EBCT as a predictor of clinical outcome in patients with chronic stable angina.


   Acknowledgements
 
We thank Pui-Ching Lee, Paulin Wu, and Man-Hui Cheng for the statistical analyses and graphic works for this study.


   Footnotes
 
Abbreviations: ANOVA = analysis of variance; CAD = coronary artery disease; CCS = coronary calcium score; EBCT = electron-beam CT; ETT = exercise treadmill test; HU = Hounsfield units; ROC = receiver operating characteristic

This work was supported by grants from Taipei Veterans General Hospital (VGH 89–029, VGH 90–011).

Received for publication September 27, 2000. Accepted for publication May 23, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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P.-H. Huang, L.-C. Chen, H.-B. Leu, P. Y.-A. Ding, J.-W. Chen, T.-C. Wu, and S.-J. Lin
Enhanced Coronary Calcification Determined by Electron Beam CT Is Strongly Related to Endothelial Dysfunction in Patients With Suspected Coronary Artery Disease
Chest, August 1, 2005; 128(2): 810 - 815.
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