RAMA-EGAT Risk Score for Predicting Coronary Artery Disease Evaluated by 64- Slice CT Angiography

RAMA-EGAT Risk Score for Predicting Coronary Artery Disease Evaluated by 64- Slice CT Angiography Supalerk Pattanaprichakul, MD 1, Sutipong Jongjirasiri, MD 2, Sukit Yamwong, MD 1, Jiraporn Laothammatas, MD 2, Piyamitr Sritara, MD 1 1 Division of Cardiology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 2 Department of Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract Background: This is the first published study investigating the prevalence of coronary artery disease (CAD) in patients with moderate to high risk for CAD in Thailand. Objectives: We prospectively investigated the prevalence of CAD using 64-slice CT coronary angiography in patients with moderate to high risk for CAD and analyzed by using the RAMA- Electricity Generating Authority of Thailand (RAMA EGAT) score. Materials and Methods: All patients with moderate to high risk for CAD by RAMA-EGAT risk score were enrolled between 1 November 2005 and 15 September 2006. 64-slice CT coronary angiography was performed to evaluate the coronary calcium score (CAC) and to detect significant coronary stenosis. Results: 1,224 patients were enrolled. 88 patients were excluded because they either declined injection of the contrast media, did not meet the inclusion criteria, or because of incomplete data. Significant coronary stenosis was detected in 282 (24.8%) patients. Of the 282 patients, 202 (17.8%) patients had moderate coronary artery stenosis (50-75% stenosis) and 80 (7.0%) patients were found to have severe coronary artery stenosis (> 75% stenosis). Thirteen (1.1%) patients were diagnosed with left main disease. Increased age group, body weight, RAMA-EGAT score, CAC, male gender, smoking, diabetes mellitus (DM) and hypertension (HT) were more frequently found in patients with significant coronary stenosis. There was a significant correlation between RAMA-EGAT score and the prevalence of coronary artery stenosis. The prevalence of significant coronary stenosis increased across increasing quintiles of RAMA-EGAT score (5.7%, 14.5%, 29.3%, 32.3%, 45.7% p<0.001) Conclusion: The RAMA-EGAT score was found to be a risk prediction for incidence of coronary artery stenosis. Our study demonstrated a good linear correlation between RAMA-EGAT score and coexisting of plaque in coronary artery. High risk subjects (with a RAMA-EGAT score 17) had a 45.7 % chance of having a significant stenosis (>50%) detected. Keywords: RAMA, EGAT, Risk score, Coronary artery disease, CT angiography ASEAN HEART J 2007; 15 : 18-22 E-Journal : http://www.aseanheartjournal.org Introduction Coronary artery disease is a leading cause of death in Thailand. The Electricity Generating Authority of Thailand (EGAT) study reported vascular disease was the most frequent cause of death during follow up and Correspondence : Supalerk Pattanaprichakul, MD. Division of Cardiology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand E mail: supalerkpat@hotmail.com correlated well with age, blood pressure, smoking, diabetes mellitus (DM), male sex, and total cholesterol. A cardiovascular score system, the RAMA-EGAT score, was devised in this study and was found to be useful in predicting cardiovascular risk in the Thai population.(1, 2) Atherosclerosis is generally asymptomatic until plaque stenosis exceeds 70-80%. But acute coronary syndromes (unstable angina, myocardial infarction, sudden death) are also often due to rupture of plaques causing as little as 50% stenosis. (3, 4) Several methods have been used to detect plaques including, coronary angiogram,

RAMA-EGAT Risk Score for Predicting Coronary Artery Disease Evaluated by 64- Slice CT Angiography 1 9 intravascular ultrasound (5, 6) and miltidetector computerized tomography (MDCT) coronary angiography. A number of studies have examined the diagnostic accuracy of 64-slice CT coronary angiography for detecting coronary artery stenosis.(7-10) To our knowledge this is the first published study in Thailand to evaluate the prevalence of coronary artery stenosis in patients with moderate to high risk factors for coronary artery disease (CAD) using the RAMA-EGAT score. Methods Study population The study population consisted of patients with suspected CAD who were referred for evaluation with 64-slice CT coronary angiography at Ramathibodi hospital between 1 November 2005 and15 September 2006. Exclusion criteria included those who declined injection of contrast media, those in whom it was contraindicated (previous allergy to contrast media, severe renal insufficiency); those with atrial fibrillation and those unable to hold their breath for long enough time for the CT scan. All patients gave informed consent. All patients were interviewed for risk factors including age, gender, history of diabetes, hypertension, dyslipidemia, smoking status, waist circumference and also were analyzed for their RAMA-EGAT score (Table 1). Table 1. 64 - slice CT coronary angiography and image interpretations All patients were scanned using a 64-slice CT scanner (Sensation 64, Siemens, Forchheim, Germany). Patients were given metoprolol 50-100 mg or propranolol 10-20 mg, 30 minutes before scanning (or diltiazem 30-60 mg if beta-blockers were contraindicated) in order to achieve a target pulse rate less than or equal to 65 beats/min. An initial unenhanced scan was performed for calcium scoring. Patients were given a bolus of 80-100 ml of contrast material (iobitridol, Xenetix 350 mgiodine/ml, Guerbet, France or iopromide, Ultravist 370 mgiodine/ml, Shering AG, Berlin, Germany) and the CT scan was triggered using a bolus tracking technique. The scan parameters were; numbers of slices per rotation 32 x 2 with individual detector width of 0.6 mm; a tube rotation time 330 ms; a table feed/rotation 3.8 mm and a tube voltage of 120 kv. A retrospective ECG-gated scan was used for image reconstruction. The images were reconstructed with data acquired during a single heartbeat. The data sets were reconstructed during the mid-to-end diastolic phase, with the reconstruction window set at -300 ms to -450 ms before the next R-wave or 60% to 70% of the R-R interval. In the case of insufficient image quality, additional reconstructions during the end-systolic phase (25%-35% of R-R interval) were performed. Score -2 0 2 3 4 5 6 8 10 Age (year) 35-39 40-44 45-49 50-54 55-59 60-65 65 Gender Female Male Cholesterol <280 >280 or (mg/dl) RAMA-EGAT score drug therapy Smoking No Yes Diabetes No Yes Hypertension No Yes Waist Below Above circumference* * Waist circumference: male 36 inches, female 32 inches

2 0 Supalerk Pattanaprichakul, MD, Sutipong Jongjirasiri, MD, Sukit Yamwong, MD, Jiraporn Laothammatas, MD, Piyamitr Sritara, MD The segments were classified according to a modified 17-segment American Heart Association (AHA) model. Computed Tomography (CT) results quantitatively evaluated the coronary lumen of all coronary segments on two projections. Coronary stenoses were scored as significant in the case of a mean lumen diameter reduction of 50% in two orthogonal projections. Moderate coronary stenosis was classified as between 50-75% coronary stenosis and severe coronary stenosis as 75% coronary stenosis. Statistical analysis Continuous variables were expressed as mean ± standard deviations (SD) and compared using the independent t-test. Categorical variables were expressed as numbers and percentages and compared between 2 groups using the chi-square test. P values <0.05 were considered statistically significant. We used linear regression analysis to correlate between the RAMA-EGAT score and significant coronary artery stenosis. Statistical analyses were performed using SPSS software version 11.5. Results Patient characteristics 1,224 patients (563 men, mean age 58.4 ± 9.2 year) were enrolled in the study. 88 patients were excluded because they either declined contrast media, had a contraindication or because their data was incomplete. Patient characteristics are provided in Table 2. 64 - slice CT coronary angiography Left main disease (>50% stenosis) was identified in 13 patients (1.1%). Significant coronary stenosis (>50% stenosis) was identified in 282 patients (24.8%), with moderate stenosis (50-75% stenosis) in 202 patients (17.8%) and severe stenosis (>75% stenosis) in 80 patients (7.0%). Coronary stenosis was divided by severity of the stenosis and the number of vessels involved (Table 3.) The majority of patients had single vessel disease. Figure 1. Prevalence of significant coronary stenosis (%) by quintile of RAMA-EGAT score Table 2. Characteristics of the study population and comparisons between patients with and without significant coronary artery stenosis Total (N = 1,224) Significant coronary stenosis No significant coronary stenosis p value (N = 282) (N = 854) Age (year) 58.4 ± 9.2 62.1 ± 8.4 56.9 ± 9.1 <0.001 BW (kg) 65 ± 11.7 67.4 ± 10.5 64 ± 11.9 <0.001 EGAT score 11.7 ± 5.5 14.5 ± 4.7 10.5 ± 5.3 <0.001 Calcium score 105.9 ± 302.7 288.2 ± 479.9 42.6 ± 162.8 <0.001 Male (%) 46 63.8 39.9 <0.001 Smoking (%) 7.3 10.3 6.7 0.047 HT (%) 42.4 55.3 36.5 <0.001 DM (%) 13.3 18.8 10 <0.001 Abdominal Obesity (%)* 31.9 39.5 28.6 0.001

RAMA-EGAT Risk Score for Predicting Coronary Artery Disease Evaluated by 64- Slice CT Angiography 2 1 Patients with significant coronary stenosis were characterized by significantly higher age, body weight, RAMA-EGAT score, coronary calcium score, male gender, smoking, DM, HT and abdominal obesity (waist circumferences more than 36 inches in male and 32 inches in female). There was a significant relationship between RAMA-EGAT score and prevalence of significant coronary stenosis. We divided patients to 5 quintiles by RAMA- EGAT score and increased prevalence of coronary stenosis was seen across increasing quintiles (5.7%, 14.5%, 29.3%, 32.3%, 45.7%, p<0.001) (Figure 1). Using linear regression analysis between RAMA-EGAT score and coronary stenosis, every one point increment of RAMA- Figure 2. Correlation between RAMA-EGAT score and percentage of significant coronary stenosis EGAT score increased the prevalence of coronary stenosis by 2.2% (constant value -1.5 and coefficient value 2.2) (Figure 2). Discussion Multislice computed tomography (MSCT) coronary angiography is a new technique for the detection of coronary stenosis. The clinical application of early models of MSCT (4 and 16 slice CT) was limited, due to the limited number of assessable vessels as a result of limited resolution and relatively long time that a breath needed to be held. 64-slice CT coronary angiography is a newer model of MSCT with improved spatial and temporal resolution. Subjects now only need to hold their breath for a short time and there is a significant improvement of image quality coupled with high accuracy [3-6]. RAMA-EGAT score has been shown to be a good predictor of cardiovascular events in the Thai population. In the present study, we also found a significant correlation between RAMA-EGAT score and significant coronary stenosis. Every risk factor used in the RAMA- EGAT score (age, sex, hypercholesterolemia (more than 280mg/dl or drug therapy), DM, HT, smoking and waist circumferences) was statistically significantly worse in those with significant coronary artery stenosis (Table 2.) In the highest risk population (RAMA-EGAT score 17), the prevalence of significant coronary stenosis was 45.7% and in the lowest risk population (RAMA-EGAT score 6), the prevalence of significant coronary stenosis Table 3. Prevalence of significant coronary stenosis divided by severity of stenosis and number of vessel involvement Frequency Percent No coronary stenosis 854 74.8 Undetermined stenosis 5 0.4 SVD moderate stenosis 152 13.3 DVD moderate stenosis 42 3.7 TVD moderate stenosis 8 0.7 SVD severe stenosis 34 3.0 DVD severe stenosis 32 2.8 TVD severe stenosis 14 1.2 Total 1,141 100

2 2 Supalerk Pattanaprichakul, MD, Sutipong Jongjirasiri, MD, Sukit Yamwong, MD, Jiraporn Laothammatas, MD, Piyamitr Sritara, MD was 5.7%. 64-slice CT coronary angiography should be beneficial in moderate to high risk populations and may be a useful guide for medical and procedure interventions. One-fourth (24.8%) of patients in this study had significant coronary stenosis and in patients with significant coronary stenosis, one-third of patients had severe coronary stenosis (>75% stenosis). Conclusions: In addition to RAMA-EGAT score was found to be a risk prediction for incidence of myocardial infarction, our study demonstrated a good linear correlation between RAMA-EGAT score and coexisting of plaque in coronary artery. The prevalence of significant coronary artery disease in high risk subjects (RAMA- EGAT score 17) was 45.7%. References 1. Sritara P, Cheepudomwit S, Chapman N, et al. Twelve-year changes in vascular risk factors and their associations with mortality in a cohort of 3499 Thais: the Electricity Generating Authority of Thailand Study. Int J Epidemiol 2003; 32: 461-8. 2. Yamwong S, et al. Final report: Total risk assessment program for cardiovascular disease from Health Research Network by National Health Foundation and The Thailand Research Fund: Clinic magazine November 2005: 319: 928-934. 3. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108: 1664-72. 4. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-8. 5. Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002; 106: 2200-6. 6. Stahr PM, Hofflinghaus T, Voigtlander T, et al. Discrimination of early/intermediate and advanced/complicated coronary plaque types by radiofrequency intravascular ultrasound analysis. Am J Cardiol 2002; 90:19-23. 7. Leber AW, Knez A, von Ziegler F, et al. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 2005; 46: 147-54. 8. Ong TK, Chin SP, Liew CK, et al. Accuracy of 64-row multidetector computed tomography in detecting coronary artery disease in 134 symptomatic patients: influence of calcification. Am Heart J 2006; 151: e1-6. 9. Pugliese F, Mollet NR, Runza G, et al. Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris. Eur Radiol 2006; 16: 575-82. 10. Gaemperli O, Schepis T, Koepfli P, et al. Accuracy of 64-slice CT angiography for the detection of functionally relevant coronary stenoses as assessed with myocardial perfusion SPECT. Eur J Nucl Med Mol Imaging 2007.