- Email: [email protected]
Increased prevalence of coronary artery calcification in patients with suspected pulmonary embolism1
Increased Prevalence of Coronary Artery Calcification in Patients with Suspected Pulmonary Embolism1 Shigeru Kiryu, MD, Vassilios Raptopoulos, MD, Jovanna Baptista, MS, Hiroto Hatabu, MD, PhD
Rationale and Objectives. The authors explored the possibility that patients with suspected pulmonary embolism are at high risk for coronary artery disease. To this purpose, they compared the presence of coronary artery calcification on computed tomography (CT) in patients suspected of pulmonary embolism with age- and gender-matched controls. Materials and Methods. The CT scans of 214 patients were reviewed. Of those, 107 consecutive patients (50%) had pulmonary CT angiography for suspected pulmonary embolism (PE group). The remaining 107 age- and gender-matched patients were scanned for reasons other than pulmonary embolism (non-PE group). All CT scans were performed with the same 8-detector–row multislice scanner. Two radiologists reviewed scans of 5-mm slices using a five-grade modified coronary calcium scoring system: 1 ⫽ no calcification; 2 ⫽ minimal calcification; 3 ⫽ mild calcification; 4 ⫽ moderate calcification; and 5 ⫽ severe calcification. The Marginal Homogeneity test was used to compare the distribution and severity of calcification in the two groups. Results. Of 107 patients in the PE group, seven (6.54%) had pulmonary embolism detected on CT. Coronary artery calcification was detected in 61 patients (57%) in the PE group compared with 42 patients (39%) in the non-PE group. The Marginal Homogeneity test showed that patients with pulmonary embolism symptoms were 2.9 times more likely to have calcification detected compared with those patients who had chest CT for some other reason (P ⫽ .0034). However, in patients in whom coronary artery calcification was detected, the distribution of severity of calcification was the same in both groups. Conclusion. Assuming coronary artery calcification indicated coronary atherosclerosis, patients undergoing CT for suspected pulmonary embolism may be at high risk for coronary artery disease. Key Words. Tomography scanners, x-ray computed; pulmonary embolism; calcification; coronary arteriosclerosis. ©
AUR, 2003
Recent applications of computed tomography (CT) include evaluation for pulmonary embolism and assessment of coronary artery disease risk (1– 4). In patients suspected for pulmonary embolism, intravenous con-
Acad Radiol 2003; 10:840 – 845 1 From the Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215 (S.K., V.R., H.H.); and AVERION, INC, Framingham, MA (J.B.). Received February 4, 2003; accepted April 21. Address correspondence to V.R.
©
AUR, 2003 doi:10.1016/S1076-6332(03)00013-8
840
trast enhanced thin-section CT is performed in the pulmonary arterial phase. In contrast, for coronary artery disease risk evaluation, the presence of coronary artery calcium is assessed and measured from thin-section nonenhanced CT obtained with electrocardiographic gating. It has recently been shown that this can be performed effectively on intravenously enhanced studies as well (5). Indications for both studies vary considerably; CT for pulmonary embolism is performed in patients with acute onset of chest pain and shortness of breath, whereas coronary calcium score is primarily used as a discriminating or screening tool for coronary
Academic Radiology, Vol 10, No 8, August 2003
artery disease risk assessment in patients without acute symptoms. With extensive use of CT for suspected pulmonary embolism at our institution, we observed low yield of positive results. We postulated that the symptoms leading to CT may have been related to coronary artery disease in many patients. Assuming patients with coronary calcium are at higher risk for coronary artery disease than those without coronary calcium, this study was undertaken to explore the possibility that patients with suspected pulmonary embolism are at high risk for coronary artery disease. To this purpose, we retrospectively reviewed scans of patients undergoing pulmonary CT angiography with age- and gender-matched controls undergoing chest CT for reasons other than suspected pulmonary embolism. Our specific goal was to statistically investigate if patients with suspected pulmonary embolism have a higher presence of coronary artery calcification on chest CT. MATERIALS AND METHODS We retrospectively reviewed the CT scans of 107 consecutive patients who had pulmonary CT angiography (PE group) from October 23 to November 26, 2002. As controls, we used 107 age- and gender-matched patients scanned during the same period of time for indications other than suspected pulmonary embolism (non-PE group). The age and gender distribution in each group by decade of life was as follows: one woman in the 2nd decade, two men and two women in the 3rd decade, six men and nine women in the 4th decade, seven men and 10 women in the 5th decade, eight men and 20 women in the 6th decade, five men and 10 women in the 7th decade, five men and nine women in the 8th decade, six men and six women in the 9th decade, and one woman in the 10th decade of life. The indications for obtaining CT of patients in the non-PE group were abnormal chest x-ray (n ⫽ 48), lung metastasis (n ⫽ 27), trauma (n ⫽ 11), primary pulmonary malignancy (n ⫽ 14), cough (n ⫽ 4), and back pain (n ⫽ 3). Both groups were scanned with the same 8-detector– row multislice CT scanner (Lightspeed Ultra; General Electric Medical Systems, Milwaukee, Wis). The PE group was scanned with 5-mm initial collimation with 13.5-mm table speed from the apex to the diaphragm; retrospective 1.25-mm axial reconstructions were performed for vessel and embolus assessment. As a routine, 100 mL of non-ionic contrast material (Optiray 320; Mallinckrodt Medical, St Louis, Mo) was given at a rate
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
of 3.5 mL/sec with a mechanical injector (Medrad, Pittsburgh, Pa). Start delay time was determined by using a test injection of 15 mL of contrast material at a rate of 3.5 mL/sec. Scanning was performed at the pulmonary arterial phase. The non-PE group was scanned with 5-mm collimation with 13.5-mm table speed from the diaphragm to the apex and retrospective 2.5-mm axial reconstructions. A total of 100 ml of non-ionic contrast material was given at a rate of 2.5 mL/sec with a mechanical injector and start delay time was 40 seconds as a routine. Other scanning parameters were as follows: 120 kV, 300340 mA, 512 ⫻ 512 matrix, and 36 cm field of view. Gantry rotation was 0.5 second in both groups. Institutional review board approval for the retrospective review of the charts and images was obtained. We were not required by the board to obtain informed consent from the patients. Each patient received a research identification number, which was used for data analysis. Presence of coronary artery calcification in each group was assessed and graded by two radiologists experienced in pulmonary CT angiography (S.K. and V.R.). They reviewed the scans together and reached a consensus. Presence of calcification was reviewed on 5-mm images at the region of the five coronary arteries: including left main, left anterior descending, circumflex, and right and posterior descending. The images were reviewed on picture archive and communication system. The following grading system for coronary artery calcification was devised: grade 1, no calcification (Fig 1a); grade 2, minimal calcification (Fig 1b); grade 3, mild calcification (Fig 1c); grade 4, moderate calcification (Fig 1d); grade 5, severe calcification (Fig 1e). Patients with grade 1 calcification were considered as not having coronary artery calcification, whereas patients with grades 2 through 5 were considered as having coronary artery calcification. Axial images were viewed in a standard mediastinal window setting (width, 400 Hounsfield Units (HU); level, 40 HU). Additionally, we continuously changed window width among 200 and 1,000 HU on a picture archive and communication system to evaluate coronary artery calcification in detail. The Marginal Homogeneity test was used to compare the distributions of calcification detection and severity in two groups. The Marginal Homogeneity test is an extension of the McNemar’s test to examine the equality of more than two binary response rates where the data are paired. In addition, the Marginal Homogeneity test is applicable to the matched pairs setting with ordered categorical data (6).
841
KIRYU ET AL
Academic Radiology, Vol 10, No 8, August 2003
Figure 1. Five-grade CT scale of coronary artery calcification. (a) Example of grade 1 or no calcification. Axial CT image obtained in a 37-year-old woman with right-sided chest pain shows no coronary artery calcification (arrow). (b) Example of grade 2 or minimal calcification. Axial CT image obtained in a 75-year-old woman with persistence having an O2 requirement that underwent a transvaginal hysterectomy shows the high-density spot with unclear demarcation at the left main coronary artery (arrow). (c) Example of grade 3 or mild calcification. Axial CT image obtained in a 56-year-old woman with acute chest pain shows short double line like the highdensity spot at the left anterior descending branch (arrow). (d) Example of grade 4 or moderate calcification. Axial CT image obtained in a 64-year-old woman with chest pain shows several high-density spots at the left anterior descending branch (arrows). (e) Example of grade 5 or severe calcification. Axial CT image obtained in a 61-year-old man with chest pain shows severe calcification at the left anterior descending branch (arrow).
842
Academic Radiology, Vol 10, No 8, August 2003
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
Table 1 Coronary Artery Calcification Detection by Age- and GenderMatched Cases and Controls* Controls (No Symptoms of PE) Cases (Symptoms of PE)
Not Detected
Detected
Total
Not Detected Detected Total
36 29 65
10 32 42
46 61 107
*Marginal Homogeneity Test exact P value ⫽ 0.0034.
Figure 2. Graph shows modified coronary calcium grading in patients undergoing pulmonary CT angiography (white column) compared with those having CT for other reasons (gray column). Grade 1, no calcification; grade 2, minimal calcification; grade 3, mild calcification; grade 4, moderate calcification; grade 5, severe calcification.
RESULTS In each group of 107 patients, 68 were women and 39 were men. Mean age and standard deviation of the patients in the PE group was 56 ⫾ 17 years (range, 16 –90 years). Mean age in the control, non-PE group, was 56 ⫾ 18 years (range, 16 –90 years). The patient distribution by coronary artery calcification grade in the PE and non-PE groups were 46 versus 65 in grade 1, 27 versus 9 in grade 2, 17 versus 11 in grade 3, 9 versus 9 in grade 4, and 8 versus 13 in grade 5 (Fig 2). Of the 107 patients with pulmonary CT angiography, seven patients (6.54%) had pulmonary embolism noted on CT and 100 did not. Five men and two women had pulmonary embolism, and their mean age was 63.4 ⫾ 14.7. In the PE group, coronary artery calcification was noted in 61 patients (57% ⫾ 6% standard error of proportion). In contrast, coronary artery calcification was seen in 42 patients (39% ⫾ 5% standard error of proportion) with PE symptoms. The Marginal Homogeneity test was used to test if coronary artery calcification detection rate varied by patients in the PE group and those in the non-PE group. The test showed that patients who had pulmonary embolism symptoms were 2.9 times more likely to have coronary artery calcification detected compared with those patients who had chest CT angiography for another reason (P ⫽ .0034). Table 1 shows the number of cases and controls by calcification detection. The Marginal Homogeneity test was also used to examine if age- and gender-matched cases and controls had
the same distribution of coronary artery calcification grades. The test showed that the two groups of patients had a similar distribution of calcification severity (P ⫽ .5672). Thus, the distribution of coronary artery calcification grades did not differ with respect to reason for chest CT (pulmonary embolism or no pulmonary embolism). Table 2 displays the number of cases and controls by calcification severity. DISCUSSION In this study, coronary artery calcification was observed in more patients with symptoms suggestive of pulmonary embolism and undergoing multislice pulmonary CT angiography than in those who had chest CT for other indications. Our patients with pulmonary embolism symptoms were 2.9 times more likely to have coronary artery calcification detected compared with those patients who had chest CT for other reasons. However, if coronary artery calcification was detected, the distribution of severity of calcification was the same in both groups.
Table 2 Coronary Artery Calcification Grade by Age- and GenderMatched Cases and Controls* Controls (No Symptoms of PE) Cases (Symptoms of PE)
1
2
3
4
5
Total
1 2 3 4 5 Total
36 17 8 3 1 65
3 1 2 2 1 9
3 3 3 1 1 11
1 3 2 1 2 9
3 3 2 2 3 13
46 27 17 9 8 107
*Marginal Homogeneity Test exact P value ⫽ 0.5672.
843
KIRYU ET AL
Chest pain and dyspnea are the most frequent symptoms of pulmonary embolism. Patients often present with tachypnea, cough, and hemoptysis (7). However, these symptoms and signs are often nonspecific and overlap with a variety of pulmonary and cardiovascular conditions (8). Accordingly, coronary artery disease may present with symptoms and signs that resemble pulmonary embolism. Furthermore, some patients may have both pulmonary embolism and coronary artery disease. Coronary artery calcification has been shown to be associated with coronary atherosclerosis (9 –11). Coronary calcium scores obtained from computer-aided measurement of coronary artery calcification on electrocardiographic gated electron beam scans are used as quantitative coronary artery disease risk factor (12). High coronary calcium scoring is associated with increased risk of coronary artery disease (13). The technique is well described, and good correlation has been shown between scoring using electrocardiographic gated electron beam, singleslice helical, and multislice CT (14,15). In this study, we showed increased prevalence of coronary artery calcification in patients undergoing CT angiography for suspected pulmonary embolism. Therefore, assuming the presence of calcification is an indicator of increased risk for coronary artery disease, careful evaluation of coronary artery disease risk factors in these patients should be considered. However, this relationship should be viewed with caution. Various studies have shown that increasing age influences the amount and progression of coronary artery calcium, and the significance for measuring calcium depends on patient age (16 –18). Furthermore, a correlation between our qualitative calcium scoring and the electrocardiographic gated method has not been shown. Because of motion artifacts, nongated CT would underestimate the degree of coronary artery calcification. It has been shown that electrocardiographic gated multislice thoracic CT has advantages over nongated CT angiography of the thoracic aorta, and thin-slice CT is superior to thick-slice pulmonary CT angiography (19,20). Multislice CT improves pulmonary artery visualization in the middle and peripheral zones (20). Our results may evoke the possibility that coronary CT angiography should be considered as an adjunct to pulmonary CT angiography. With minor protocol adjustments and the use of faster, ⱖ16-detector–row multislice CT, integrated pulmonary and coronary artery evaluation with the same intravenous bolus load and CT data set could be developed. In recent studies, pulmonary embolism has been detected in 20%–36% of patients undergoing pulmonary CT
844
Academic Radiology, Vol 10, No 8, August 2003
angiography (21–23). In our study, only seven of 107 patients (6.54%) had pulmonary embolism. The lower prevalence of embolism in our patients may reflect the increased popularity of pulmonary CT angiography among referring physician who may have developed a low threshold in ordering this test. Kim et al (8) showed important findings in 57 of 85 patients who had no pulmonary embolism on CT angiography. Thus, pulmonary embolism may have shifted from the only indication for pulmonary CT angiography to one that is included in a much broader clinical differential diagnosis. Therefore, the finding of increased coronary artery disease risk in these patients may be important. This is a retrospective study and thus limited by selection bias (24). With the decreasing threshold in performing CT angiography for suspected pulmonary embolism, the patients in our study may not have been representative of the disease. To reduce this limitation, we selected sequential patients undergoing pulmonary CT angiography and compared them with age- and gender-matched patients undergoing conventional CT during the same chronologic period.
CONCLUSION Our data suggest that significant numbers of patients undergoing pulmonary CT angiography for suspected pulmonary embolism are at high risk for coronary artery disease. Further confirmation of this observation is warranted whereas new protocols may produce an integrated pulmonary and coronary artery CT angiography study. REFERENCES 1. Kopp AF, Ohnesorge B, Becker C, et al. Reproducibility and accuracy of coronary calcium measurements with multi-detector row versus electron-beam CT. Radiology 2002; 225:113–119. 2. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995; 92:2157–2162. 3. Remy-Jardin M, Remy J, Baghaie F, Fribourg M, Artaud D, Duhamel A. Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. AJR Am J Roentgenol 2000; 175:407– 411. 4. Tillie-Leblond I, Mastora I, Radenne F, et al. Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology 2002; 223:461– 467. 5. Hong C, Becker CR, Schoepf UJ, Ohnesorge B, Bruening R, Reiser MF. Coronary artery calcium: absolute quantification in nonenhanced and contrast-enhanced multi-detector row CT studies. Radiology 2002; 223:474 – 480. 6. Agresti A. Models for matched pairs. In: Wiley Series in Probability and Mathematical Statistics Applied Probability and Statistics Categorical Data Analysis. New York: John Wiley & Sons, 1990:358 –365.
Academic Radiology, Vol 10, No 8, August 2003
7. Manganelli D, Palla A, Donnamaria V, Giuntini C. Clinical features of pulmonary embolism. Doubts and certainties. Chest 1995; 107:25S– 32S. 8. Kim KI, Muller NL, Mayo JR. Clinically suspected pulmonary embolism: utility of spiral CT. Radiology 1999; 210:693– 697. 9. Rifkin RD, Parisi AF, Folland E. Coronary calcification in the diagnosis of coronary artery disease. Am J Cardiol 1979; 44:141–147. 10. Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates. JAMA 1994; 271:289 –294. 11. Frink RJ, Achor RW, Brown AL Jr, Kincaid OW, Brandenburg RO. Significance of calcification of the coronary arteries. Am J Cardiol 1970; 26:241–247. 12. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15:827– 832. 13. Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association Writing Group. Circulation 1996; 94:1175–1192. 14. Becker CR, Jakobs TF, Aydemir S, et al. Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification. AJR Am J Roentgenol 2000; 174:543–547. 15. Horiguchi J, Nakanishi T, Ito K. Quantification of coronary artery calcium using multidetector CT and a retrospective ECG-gating reconstruction algorithm. AJR Am J Roentgenol 2001; 177:1429 –1435. 16. Janowitz WR, Agatston AS, Kaplan G, Viamonte M Jr. Differences in prevalence and extent of coronary artery calcium detected by ultrafast
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
17.
18.
19. 20.
21.
22.
23.
24.
computed tomography in asymptomatic men and women. Am J Cardiol 1993; 72:247–254. Wong ND, Kouwabunpat D, Vo AN, et al. Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. Am Heart J 1994; 127: 422– 430. Devries S, Wolfkiel C, Fusman B, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol 1995; 25:76 – 82. Schoepf UJ, Kessler MA, Rieger CT, et al. Multislice CT imaging of pulmonary embolism. Eur Radiol 2001; 11:2278 –2286. Raptopoulos V, Boiselle PM. Multi-detector row spiral CT pulmonary angiography: comparison with single-detector row spiral CT. Radiology 2001; 221:606 – 613. Goodman LR, Lipchik RJ, Kuzo RS, Liu Y, McAuliffe TL, O’Brien DJ. Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram—prospective comparison with scintigraphy. Radiology 2000; 215:535–542. Gottsater A, Berg A, Centergard J, Frennby B, Nirhov N, Nyman U. Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT? Eur Radiol 2001; 11:65–72. Garg K, Sieler H, Welsh CH, Johnston RJ, Russ PD. Clinical validity of helical CT being interpreted as negative for pulmonary embolism: implications for patient treatment. AJR Am J Roentgenol 1999; 172:1627–1631. Black WC. How to evaluate the radiology literature. AJR Am J Roentgenol 1990; 154:17–22.
845
Rationale and Objectives. The authors explored the possibility that patients with suspected pulmonary embolism are at high risk for coronary artery disease. To this purpose, they compared the presence of coronary artery calcification on computed tomography (CT) in patients suspected of pulmonary embolism with age- and gender-matched controls. Materials and Methods. The CT scans of 214 patients were reviewed. Of those, 107 consecutive patients (50%) had pulmonary CT angiography for suspected pulmonary embolism (PE group). The remaining 107 age- and gender-matched patients were scanned for reasons other than pulmonary embolism (non-PE group). All CT scans were performed with the same 8-detector–row multislice scanner. Two radiologists reviewed scans of 5-mm slices using a five-grade modified coronary calcium scoring system: 1 ⫽ no calcification; 2 ⫽ minimal calcification; 3 ⫽ mild calcification; 4 ⫽ moderate calcification; and 5 ⫽ severe calcification. The Marginal Homogeneity test was used to compare the distribution and severity of calcification in the two groups. Results. Of 107 patients in the PE group, seven (6.54%) had pulmonary embolism detected on CT. Coronary artery calcification was detected in 61 patients (57%) in the PE group compared with 42 patients (39%) in the non-PE group. The Marginal Homogeneity test showed that patients with pulmonary embolism symptoms were 2.9 times more likely to have calcification detected compared with those patients who had chest CT for some other reason (P ⫽ .0034). However, in patients in whom coronary artery calcification was detected, the distribution of severity of calcification was the same in both groups. Conclusion. Assuming coronary artery calcification indicated coronary atherosclerosis, patients undergoing CT for suspected pulmonary embolism may be at high risk for coronary artery disease. Key Words. Tomography scanners, x-ray computed; pulmonary embolism; calcification; coronary arteriosclerosis. ©
AUR, 2003
Recent applications of computed tomography (CT) include evaluation for pulmonary embolism and assessment of coronary artery disease risk (1– 4). In patients suspected for pulmonary embolism, intravenous con-
Acad Radiol 2003; 10:840 – 845 1 From the Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215 (S.K., V.R., H.H.); and AVERION, INC, Framingham, MA (J.B.). Received February 4, 2003; accepted April 21. Address correspondence to V.R.
©
AUR, 2003 doi:10.1016/S1076-6332(03)00013-8
840
trast enhanced thin-section CT is performed in the pulmonary arterial phase. In contrast, for coronary artery disease risk evaluation, the presence of coronary artery calcium is assessed and measured from thin-section nonenhanced CT obtained with electrocardiographic gating. It has recently been shown that this can be performed effectively on intravenously enhanced studies as well (5). Indications for both studies vary considerably; CT for pulmonary embolism is performed in patients with acute onset of chest pain and shortness of breath, whereas coronary calcium score is primarily used as a discriminating or screening tool for coronary
Academic Radiology, Vol 10, No 8, August 2003
artery disease risk assessment in patients without acute symptoms. With extensive use of CT for suspected pulmonary embolism at our institution, we observed low yield of positive results. We postulated that the symptoms leading to CT may have been related to coronary artery disease in many patients. Assuming patients with coronary calcium are at higher risk for coronary artery disease than those without coronary calcium, this study was undertaken to explore the possibility that patients with suspected pulmonary embolism are at high risk for coronary artery disease. To this purpose, we retrospectively reviewed scans of patients undergoing pulmonary CT angiography with age- and gender-matched controls undergoing chest CT for reasons other than suspected pulmonary embolism. Our specific goal was to statistically investigate if patients with suspected pulmonary embolism have a higher presence of coronary artery calcification on chest CT. MATERIALS AND METHODS We retrospectively reviewed the CT scans of 107 consecutive patients who had pulmonary CT angiography (PE group) from October 23 to November 26, 2002. As controls, we used 107 age- and gender-matched patients scanned during the same period of time for indications other than suspected pulmonary embolism (non-PE group). The age and gender distribution in each group by decade of life was as follows: one woman in the 2nd decade, two men and two women in the 3rd decade, six men and nine women in the 4th decade, seven men and 10 women in the 5th decade, eight men and 20 women in the 6th decade, five men and 10 women in the 7th decade, five men and nine women in the 8th decade, six men and six women in the 9th decade, and one woman in the 10th decade of life. The indications for obtaining CT of patients in the non-PE group were abnormal chest x-ray (n ⫽ 48), lung metastasis (n ⫽ 27), trauma (n ⫽ 11), primary pulmonary malignancy (n ⫽ 14), cough (n ⫽ 4), and back pain (n ⫽ 3). Both groups were scanned with the same 8-detector– row multislice CT scanner (Lightspeed Ultra; General Electric Medical Systems, Milwaukee, Wis). The PE group was scanned with 5-mm initial collimation with 13.5-mm table speed from the apex to the diaphragm; retrospective 1.25-mm axial reconstructions were performed for vessel and embolus assessment. As a routine, 100 mL of non-ionic contrast material (Optiray 320; Mallinckrodt Medical, St Louis, Mo) was given at a rate
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
of 3.5 mL/sec with a mechanical injector (Medrad, Pittsburgh, Pa). Start delay time was determined by using a test injection of 15 mL of contrast material at a rate of 3.5 mL/sec. Scanning was performed at the pulmonary arterial phase. The non-PE group was scanned with 5-mm collimation with 13.5-mm table speed from the diaphragm to the apex and retrospective 2.5-mm axial reconstructions. A total of 100 ml of non-ionic contrast material was given at a rate of 2.5 mL/sec with a mechanical injector and start delay time was 40 seconds as a routine. Other scanning parameters were as follows: 120 kV, 300340 mA, 512 ⫻ 512 matrix, and 36 cm field of view. Gantry rotation was 0.5 second in both groups. Institutional review board approval for the retrospective review of the charts and images was obtained. We were not required by the board to obtain informed consent from the patients. Each patient received a research identification number, which was used for data analysis. Presence of coronary artery calcification in each group was assessed and graded by two radiologists experienced in pulmonary CT angiography (S.K. and V.R.). They reviewed the scans together and reached a consensus. Presence of calcification was reviewed on 5-mm images at the region of the five coronary arteries: including left main, left anterior descending, circumflex, and right and posterior descending. The images were reviewed on picture archive and communication system. The following grading system for coronary artery calcification was devised: grade 1, no calcification (Fig 1a); grade 2, minimal calcification (Fig 1b); grade 3, mild calcification (Fig 1c); grade 4, moderate calcification (Fig 1d); grade 5, severe calcification (Fig 1e). Patients with grade 1 calcification were considered as not having coronary artery calcification, whereas patients with grades 2 through 5 were considered as having coronary artery calcification. Axial images were viewed in a standard mediastinal window setting (width, 400 Hounsfield Units (HU); level, 40 HU). Additionally, we continuously changed window width among 200 and 1,000 HU on a picture archive and communication system to evaluate coronary artery calcification in detail. The Marginal Homogeneity test was used to compare the distributions of calcification detection and severity in two groups. The Marginal Homogeneity test is an extension of the McNemar’s test to examine the equality of more than two binary response rates where the data are paired. In addition, the Marginal Homogeneity test is applicable to the matched pairs setting with ordered categorical data (6).
841
KIRYU ET AL
Academic Radiology, Vol 10, No 8, August 2003
Figure 1. Five-grade CT scale of coronary artery calcification. (a) Example of grade 1 or no calcification. Axial CT image obtained in a 37-year-old woman with right-sided chest pain shows no coronary artery calcification (arrow). (b) Example of grade 2 or minimal calcification. Axial CT image obtained in a 75-year-old woman with persistence having an O2 requirement that underwent a transvaginal hysterectomy shows the high-density spot with unclear demarcation at the left main coronary artery (arrow). (c) Example of grade 3 or mild calcification. Axial CT image obtained in a 56-year-old woman with acute chest pain shows short double line like the highdensity spot at the left anterior descending branch (arrow). (d) Example of grade 4 or moderate calcification. Axial CT image obtained in a 64-year-old woman with chest pain shows several high-density spots at the left anterior descending branch (arrows). (e) Example of grade 5 or severe calcification. Axial CT image obtained in a 61-year-old man with chest pain shows severe calcification at the left anterior descending branch (arrow).
842
Academic Radiology, Vol 10, No 8, August 2003
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
Table 1 Coronary Artery Calcification Detection by Age- and GenderMatched Cases and Controls* Controls (No Symptoms of PE) Cases (Symptoms of PE)
Not Detected
Detected
Total
Not Detected Detected Total
36 29 65
10 32 42
46 61 107
*Marginal Homogeneity Test exact P value ⫽ 0.0034.
Figure 2. Graph shows modified coronary calcium grading in patients undergoing pulmonary CT angiography (white column) compared with those having CT for other reasons (gray column). Grade 1, no calcification; grade 2, minimal calcification; grade 3, mild calcification; grade 4, moderate calcification; grade 5, severe calcification.
RESULTS In each group of 107 patients, 68 were women and 39 were men. Mean age and standard deviation of the patients in the PE group was 56 ⫾ 17 years (range, 16 –90 years). Mean age in the control, non-PE group, was 56 ⫾ 18 years (range, 16 –90 years). The patient distribution by coronary artery calcification grade in the PE and non-PE groups were 46 versus 65 in grade 1, 27 versus 9 in grade 2, 17 versus 11 in grade 3, 9 versus 9 in grade 4, and 8 versus 13 in grade 5 (Fig 2). Of the 107 patients with pulmonary CT angiography, seven patients (6.54%) had pulmonary embolism noted on CT and 100 did not. Five men and two women had pulmonary embolism, and their mean age was 63.4 ⫾ 14.7. In the PE group, coronary artery calcification was noted in 61 patients (57% ⫾ 6% standard error of proportion). In contrast, coronary artery calcification was seen in 42 patients (39% ⫾ 5% standard error of proportion) with PE symptoms. The Marginal Homogeneity test was used to test if coronary artery calcification detection rate varied by patients in the PE group and those in the non-PE group. The test showed that patients who had pulmonary embolism symptoms were 2.9 times more likely to have coronary artery calcification detected compared with those patients who had chest CT angiography for another reason (P ⫽ .0034). Table 1 shows the number of cases and controls by calcification detection. The Marginal Homogeneity test was also used to examine if age- and gender-matched cases and controls had
the same distribution of coronary artery calcification grades. The test showed that the two groups of patients had a similar distribution of calcification severity (P ⫽ .5672). Thus, the distribution of coronary artery calcification grades did not differ with respect to reason for chest CT (pulmonary embolism or no pulmonary embolism). Table 2 displays the number of cases and controls by calcification severity. DISCUSSION In this study, coronary artery calcification was observed in more patients with symptoms suggestive of pulmonary embolism and undergoing multislice pulmonary CT angiography than in those who had chest CT for other indications. Our patients with pulmonary embolism symptoms were 2.9 times more likely to have coronary artery calcification detected compared with those patients who had chest CT for other reasons. However, if coronary artery calcification was detected, the distribution of severity of calcification was the same in both groups.
Table 2 Coronary Artery Calcification Grade by Age- and GenderMatched Cases and Controls* Controls (No Symptoms of PE) Cases (Symptoms of PE)
1
2
3
4
5
Total
1 2 3 4 5 Total
36 17 8 3 1 65
3 1 2 2 1 9
3 3 3 1 1 11
1 3 2 1 2 9
3 3 2 2 3 13
46 27 17 9 8 107
*Marginal Homogeneity Test exact P value ⫽ 0.5672.
843
KIRYU ET AL
Chest pain and dyspnea are the most frequent symptoms of pulmonary embolism. Patients often present with tachypnea, cough, and hemoptysis (7). However, these symptoms and signs are often nonspecific and overlap with a variety of pulmonary and cardiovascular conditions (8). Accordingly, coronary artery disease may present with symptoms and signs that resemble pulmonary embolism. Furthermore, some patients may have both pulmonary embolism and coronary artery disease. Coronary artery calcification has been shown to be associated with coronary atherosclerosis (9 –11). Coronary calcium scores obtained from computer-aided measurement of coronary artery calcification on electrocardiographic gated electron beam scans are used as quantitative coronary artery disease risk factor (12). High coronary calcium scoring is associated with increased risk of coronary artery disease (13). The technique is well described, and good correlation has been shown between scoring using electrocardiographic gated electron beam, singleslice helical, and multislice CT (14,15). In this study, we showed increased prevalence of coronary artery calcification in patients undergoing CT angiography for suspected pulmonary embolism. Therefore, assuming the presence of calcification is an indicator of increased risk for coronary artery disease, careful evaluation of coronary artery disease risk factors in these patients should be considered. However, this relationship should be viewed with caution. Various studies have shown that increasing age influences the amount and progression of coronary artery calcium, and the significance for measuring calcium depends on patient age (16 –18). Furthermore, a correlation between our qualitative calcium scoring and the electrocardiographic gated method has not been shown. Because of motion artifacts, nongated CT would underestimate the degree of coronary artery calcification. It has been shown that electrocardiographic gated multislice thoracic CT has advantages over nongated CT angiography of the thoracic aorta, and thin-slice CT is superior to thick-slice pulmonary CT angiography (19,20). Multislice CT improves pulmonary artery visualization in the middle and peripheral zones (20). Our results may evoke the possibility that coronary CT angiography should be considered as an adjunct to pulmonary CT angiography. With minor protocol adjustments and the use of faster, ⱖ16-detector–row multislice CT, integrated pulmonary and coronary artery evaluation with the same intravenous bolus load and CT data set could be developed. In recent studies, pulmonary embolism has been detected in 20%–36% of patients undergoing pulmonary CT
844
Academic Radiology, Vol 10, No 8, August 2003
angiography (21–23). In our study, only seven of 107 patients (6.54%) had pulmonary embolism. The lower prevalence of embolism in our patients may reflect the increased popularity of pulmonary CT angiography among referring physician who may have developed a low threshold in ordering this test. Kim et al (8) showed important findings in 57 of 85 patients who had no pulmonary embolism on CT angiography. Thus, pulmonary embolism may have shifted from the only indication for pulmonary CT angiography to one that is included in a much broader clinical differential diagnosis. Therefore, the finding of increased coronary artery disease risk in these patients may be important. This is a retrospective study and thus limited by selection bias (24). With the decreasing threshold in performing CT angiography for suspected pulmonary embolism, the patients in our study may not have been representative of the disease. To reduce this limitation, we selected sequential patients undergoing pulmonary CT angiography and compared them with age- and gender-matched patients undergoing conventional CT during the same chronologic period.
CONCLUSION Our data suggest that significant numbers of patients undergoing pulmonary CT angiography for suspected pulmonary embolism are at high risk for coronary artery disease. Further confirmation of this observation is warranted whereas new protocols may produce an integrated pulmonary and coronary artery CT angiography study. REFERENCES 1. Kopp AF, Ohnesorge B, Becker C, et al. Reproducibility and accuracy of coronary calcium measurements with multi-detector row versus electron-beam CT. Radiology 2002; 225:113–119. 2. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995; 92:2157–2162. 3. Remy-Jardin M, Remy J, Baghaie F, Fribourg M, Artaud D, Duhamel A. Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. AJR Am J Roentgenol 2000; 175:407– 411. 4. Tillie-Leblond I, Mastora I, Radenne F, et al. Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology 2002; 223:461– 467. 5. Hong C, Becker CR, Schoepf UJ, Ohnesorge B, Bruening R, Reiser MF. Coronary artery calcium: absolute quantification in nonenhanced and contrast-enhanced multi-detector row CT studies. Radiology 2002; 223:474 – 480. 6. Agresti A. Models for matched pairs. In: Wiley Series in Probability and Mathematical Statistics Applied Probability and Statistics Categorical Data Analysis. New York: John Wiley & Sons, 1990:358 –365.
Academic Radiology, Vol 10, No 8, August 2003
7. Manganelli D, Palla A, Donnamaria V, Giuntini C. Clinical features of pulmonary embolism. Doubts and certainties. Chest 1995; 107:25S– 32S. 8. Kim KI, Muller NL, Mayo JR. Clinically suspected pulmonary embolism: utility of spiral CT. Radiology 1999; 210:693– 697. 9. Rifkin RD, Parisi AF, Folland E. Coronary calcification in the diagnosis of coronary artery disease. Am J Cardiol 1979; 44:141–147. 10. Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates. JAMA 1994; 271:289 –294. 11. Frink RJ, Achor RW, Brown AL Jr, Kincaid OW, Brandenburg RO. Significance of calcification of the coronary arteries. Am J Cardiol 1970; 26:241–247. 12. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15:827– 832. 13. Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association Writing Group. Circulation 1996; 94:1175–1192. 14. Becker CR, Jakobs TF, Aydemir S, et al. Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification. AJR Am J Roentgenol 2000; 174:543–547. 15. Horiguchi J, Nakanishi T, Ito K. Quantification of coronary artery calcium using multidetector CT and a retrospective ECG-gating reconstruction algorithm. AJR Am J Roentgenol 2001; 177:1429 –1435. 16. Janowitz WR, Agatston AS, Kaplan G, Viamonte M Jr. Differences in prevalence and extent of coronary artery calcium detected by ultrafast
CORONARY ARTERY CALCIFICATION IN SUSPECTED PE
17.
18.
19. 20.
21.
22.
23.
24.
computed tomography in asymptomatic men and women. Am J Cardiol 1993; 72:247–254. Wong ND, Kouwabunpat D, Vo AN, et al. Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. Am Heart J 1994; 127: 422– 430. Devries S, Wolfkiel C, Fusman B, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol 1995; 25:76 – 82. Schoepf UJ, Kessler MA, Rieger CT, et al. Multislice CT imaging of pulmonary embolism. Eur Radiol 2001; 11:2278 –2286. Raptopoulos V, Boiselle PM. Multi-detector row spiral CT pulmonary angiography: comparison with single-detector row spiral CT. Radiology 2001; 221:606 – 613. Goodman LR, Lipchik RJ, Kuzo RS, Liu Y, McAuliffe TL, O’Brien DJ. Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram—prospective comparison with scintigraphy. Radiology 2000; 215:535–542. Gottsater A, Berg A, Centergard J, Frennby B, Nirhov N, Nyman U. Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT? Eur Radiol 2001; 11:65–72. Garg K, Sieler H, Welsh CH, Johnston RJ, Russ PD. Clinical validity of helical CT being interpreted as negative for pulmonary embolism: implications for patient treatment. AJR Am J Roentgenol 1999; 172:1627–1631. Black WC. How to evaluate the radiology literature. AJR Am J Roentgenol 1990; 154:17–22.
845