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(Circulation. 2000;101:244.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Severity of Coronary Artery Calcification by Electron Beam Computed Tomography Predicts Silent Myocardial Ischemia

Presented in part at the 46th Annual Scientific Session, American College of Cardiology, Anaheim, Calif, March 19, 1997.

Zuo-Xiang He, MD; Thomas D. Hedrick, MD; Craig M. Pratt, MD; Mario S. Verani, MD; Vincent Aquino, MD; Robert Roberts, MD; John J. Mahmarian, MD

From the Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College, Beijing, China (Z.-X.H.); Baylor College of Medicine, Houston, Tex (T.D.H., C.M.P., M.S.V., R.R., J.J.M.); and North Houston Heart Center, Houston, Tex (V.A.).

	Abstract

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Background—Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia.

Methods and Results—Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS <10 had an abnormal SPECT compared with 2.6% of those with scores from 11 to 100, 11.3% of those with scores from 101 to 399, and 46% of those with scores 400 (P<0.0001). CACS predicted an abnormal SPECT regardless of subject age or sex.

Conclusions—CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Key Words: tomography • calcium • ischemia

	Introduction

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The detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. However, currently available noninvasive techniques, such as exercise treadmill testing (ETT) and myocardial single photon emission computed tomography (SPECT), can identify only patients with advanced CAD who manifest myocardial ischemia.^{1 2} Although the presence and extent of left ventricular ischemia can accurately identify individuals at high risk for cardiac events,^{3 4 5 6 7 8} the low prevalence of a positive test result among asymptomatic subjects with cardiac risk factors mitigates against this approach.^{7 8 9}

Electron beam computed tomography (EBCT) is a new noninvasive technique that can detect coronary atherosclerosis even at its earliest stages on the basis of the presence and severity of coronary artery calcification.¹⁰ Although calcification severity predicts the presence of significant anatomic CAD,^{11 12} there is little information as to whether the coronary artery calcium score (CACS) can identify asymptomatic individuals at high risk for having myocardial ischemia among a larger, asymptomatic, heterogeneous population with cardiac risk factors.¹² This is clinically important because the presence and extent of left ventricular ischemia predict outcome beyond that provided by coronary angiographic findings alone.^{4 5 13}

Accordingly, the purpose of this study was to determine whether EBCT could identify subjects with scintigraphic ischemia on the basis of CACS severity and thereby define its role as a primary screening technique for identifying subjects with a broad spectrum of CAD.

	Methods

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Study Population
From December 1995 to May 1998, 3895 subjects had EBCT at our imaging center; 411 also had stress SPECT within a close temporal period (median, 17 days) to detect myocardial ischemia (Table 1). Individuals who had an abnormal EBCT were encouraged to have SPECT; however, we did not seek to identify subjects who had SPECT at institutions other than our own. Most of the 411 subjects (87%) were entirely asymptomatic although 54 (13%) had various nonanginal chest pain symptoms. All subjects had risk factors known to promote the development of CAD (Table 1). The baseline characteristics of subjects with and without a history of atypical chest pain were generally similar (Table 2).

View this table: [in this window] [in a new window]   Table 1. Demographic and EBCT Results

View this table: [in this window] [in a new window]   Table 2. Demographic and EBCT Results in Subjects With and Without Chest Pain

EBCT Study
EBCT was performed on an Imatron C-150 ultrafast CT scanner with a 100-ms exposure time and 30-cm field size. With ECG gating, 32 consecutive images were obtained in diastole at 3-mm intervals. Coronary calcification was defined as a lesion of >130 Hounsfield units with an area >1.02 mm; lesions were manually planimetered by an experienced technologist and reviewed by a radiologist (T.D.H.). CACS was determined for the 4 main coronary arteries and then summed to generate a total score. The Agatston score was defined as normal, mild, moderate, or severe on the basis of total CACS and subject age and sex.¹⁴ We also performed analysis using a more recently proposed scoring system based on the total CACS: 0 (normal), 1 to 10 (minimal), 11 to 100 (mild), 101 to 399 (moderate), and 400 (severe).¹⁵

SPECT Study
Standard stress and rest SPECT were performed with ²⁰¹Tl (67%), ^99mTc sestamibi (21%), or tetrofosmin (12%).^{2 16} Symptom-limited ETT by use of the Bruce protocol was performed in 352 subjects (86%), whereas 11% received adenosine¹⁷ and 3% received dobutamine¹⁸ with standard infusion protocols. ECG ischemia was defined as a 1-mm ST-segment depression occurring 80 ms after the J point. All exercise ECGs were interpreted by researchers who had no knowledge of EBCT or SPECT results. We excluded 10 subjects because of lack of stress ECG data (n=3), left ventricular hypertrophy (n=6), or left bundle-branch block (n=1). A standard Duke treadmill score was calculated in the remaining 342 subjects and defined as low (5), moderate (-10 to 4), or high (-11) risk.¹⁹

Stress and rest SPECT images were acquired by use of a large-field-of-view rotating gamma camera equipped with a high-resolution, parallel-hole collimator.^{2 16} Images were computer quantified and displayed as polar maps by an experienced investigator (J.J.M.) who had no knowledge of the EBCT or ETT results.^{2 5} Raw data polar maps for each subject were statistically compared with those in a corresponding stressor and radiopharmaceutical specific normal data bank to determine total left ventricular perfusion defect size and the extent of scar and ischemia. Perfusion defects were localized to specific vascular territories, and a 3% focal defect was considered abnormal.² A 15% stress-induced perfusion defect defined high risk for cardiac events.^{3 4}

Statistical Analysis
Unpaired t tests were used to compare (1) clinical and EBCT variables in subjects who did or did not have SPECT (Table 1) and (2) EBCT, SPECT, and ETT variables in those who had all tests. Discrete data variables were examined by use of ² analysis. Stepwise logistic regression (Minitab for Windows 95) identified variables independently associated with abnormalities on SPECT. Demographic, EBCT (Table 1), and ETT variables were considered potential factors for an abnormal SPECT. Variables entered and remained in the model if the value for an association was P<0.05. A value of P<0.05 was considered significant. All data are presented as mean±SD.

	Results

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EBCT Results
The 411 subjects studied with EBCT and SPECT had a mean CACS of 440±640 (range, 0 to 4611). Calcium was present in the left main artery in 98 subjects (24%) and in the left anterior descending, right, and circumflex arteries in 358 (87%), 294 (72%), and 244 (59%), respectively. Fifteen percent of subjects had calcium in 1 artery, 18% in 2, 40% in 3, and 18% in all 4 major coronary arteries.

By the Agatston scoring system, 37 subjects (9%) were normal and 60 (14.6%) had mild, 155 (37.7%) had moderate, and 159 (38.7%) had severe CACS. On the basis of absolute CACS, 37 subjects (9%) had no calcium and 19 (4.6%) had minimal (1 to 10), 76 (18.5%) had mild (11 to 100), 142 (34.5%) had moderate (101 to 399), and 137 (33.4%) had severe (400) calcium. CACS results for the 411 subjects who had SPECT and the 3484 who did not are shown in Table 1; 25% and 35% of all subjects with moderate (101 to 399) or severe (400) CACS had SPECT compared with 4.5% of subjects with CACS 100.

ETT Results
The mean exercise duration for all subjects was 10±5 minutes, and 17.5% had ECG ischemia. The Duke score was low in 273 subjects (80%), moderate in 65 (19%), and high in only 4 (1%).

SPECT Results
Of 411 subjects, 81 had an abnormal SPECT with perfusion defects in the left anterior descending (n=24), right (n=28), and circumflex (n=45) coronary artery vascular territories. The overall mean defect size was 3.8±8.0% (range, 0% to 48%) and 13.5±10.6% in those who had an abnormal SPECT. Large (15%) defects were observed in 23 of 411 subjects (5.6%).

Comparison of EBCT and SPECT
The mean CACS was significantly higher in subjects who had an abnormal (1065±983) compared with a normal (286±394, P<0.00001) SPECT. CACS was also significantly higher in coronary arteries that supplied abnormally (339±491) compared with normally (124±237, P<0.0001) perfused myocardium. On the basis of Agatston score, only 1 of 97 subjects (1%) with a normal or mildly abnormal EBCT had an abnormal SPECT compared with 16 (10%) and 64 (40%) of those with a moderate or severe score, respectively (P<0.001).

Absolute CACS results are shown in Figure 1. No one with CACS 10 had an abnormal SPECT compared with 81 of 355 (23%) with higher scores. Only 2 of 76 subjects (2.6%) with mild CACS and 16 of 142 (11.3%) with a moderate score had an abnormal SPECT. All had ischemia localized to 1 vascular bed, and only 2 had a large (15%) stress-induced perfusion defect. Conversely, 63 of 137 subjects (46%) with severe CACS had an abnormal SPECT, which involved multiple vascular beds in 15 subjects (24%). Large (15%) perfusion defects were observed in a significantly greater number of subjects with severe (21 of 137, 15.3%) compared with moderate (1 of 142, 0.7%) CACS (P<0.0001).

View larger version (44K): [in this window] [in a new window]   Figure 1. SPECT results based on total CACS. Few subjects with CACS <400 had abnormal SPECT (6.6%), and most (99.3%) had only small (<15%) perfusion defect size (PDS). LV indicates left ventricle.

In the subgroup of 357 entirely asymptomatic subjects, abnormal SPECT results were similar to those found in the total cohort: 1 of 111 (0.9%) with a score 100, 12 of 122 (9.8%) with a score of 101 to 399, and 59 of 124 (47.6%) with a score 400. Likewise, only 1 of 122 (0.8%) asymptomatic subjects with moderate CACS had a large (15%) perfusion defect compared with 19 of 124 (15.3%) of those with a severe score (P<0.001).

CACS predicted an abnormal SPECT regardless of subject age or sex although women with severe CACS were less likely to have an abnormal SPECT compared with men (16% versus 51%, P=0.004; Table 3). An abnormal SPECT was again observed predominantly in subjects with CACS 400. In the total population of 3895 subjects, only a minority (10%) had a score 400 (Table 1).

View this table: [in this window] [in a new window]   Table 3. Abnormal SPECT Results Based on Age, Sex, and CACS

Exercise SPECT Versus EBCT
Most subjects who performed ETT had a normal SPECT and stress ECG (71%) and a low-risk Duke treadmill score (68%). However, 15% of 338 subjects with a low- or moderate-risk Duke score had an abnormal SPECT, and 16 (4.7%) had large (15%) perfusion defects. Few of the 342 subjects had an abnormal SPECT and concomitant ECG ischemia (4.4%) or a high-risk Duke score (1%).

Although a similar percentage of subjects had an abnormal SPECT (16.1%) or stress ECG (17.5%, P=NS), only the former was related to total CACS (Figure 2). No one with a score 100 had an abnormal SPECT compared with 40% of those with scores 400; an abnormal exercise ECG was observed across a wide spectrum of CACS severity (Figure 2). The mean CACS was significantly lower in subjects with a normal compared with an abnormal SPECT regardless of the exercise ECG findings (Figure 3). The Duke treadmill score significantly decreased as CACS increased from 100 (9.05±4.5) to 101 to 399 (7.89±4.5) to 400 (6.48±6.25, P<0.007; Figure 4). Yet the vast majority of subjects had either a low- or moderate-risk Duke score that was evenly distributed across all CACS severities (Figure 4). A representative subject with severe CACS who had discordant SPECT and exercise ECG results is shown in Figure 5.

View larger version (43K): [in this window] [in a new window]   Figure 2. Exercise SPECT and ECG results based on total CACS.

View larger version (47K): [in this window] [in a new window]   Figure 3. Mean±SD CACS based on exercise SPECT and ETT results. indicates normal; , abnormal.

View larger version (42K): [in this window] [in a new window]   Figure 4. Duke score results based on total CACS. Mean±SD Duke scores for each CACS group are shown above bar graphs. PTS indicates patients.

View larger version (87K): [in this window] [in a new window]   Figure 5. EBCT (top) and SPECT (bottom) images of asymptomatic subject who had high-risk CACS of 937. Circles define regions of coronary calcification. Upsloping (<1 mm) ST-segment depression occurred 9.0 minutes into ETT, which was terminated because of patient fatigue. Although Duke score was calculated as low risk (6.5), SPECT demonstrated large, reversible 48% perfusion defect (green) within distribution of all 3 major coronary arteries (COMP-SC) (bottom). This patient had severe 3-vessel disease on angiography and underwent CABG. PDS indicates perfusion defect size.

Predictors of an Abnormal SPECT
Total CACS was an important univariate predictor of an abnormal SPECT (Table 4). By logistic regression, CACS was the best single predictor of an abnormal SPECT (P<0.0001), followed by male sex (P<0.01) and diabetes mellitus (P<0.01). In those who performed ETT, total CACS was again the best predictor (P<0.0001), followed by male sex (P<0.05) and maximal exercise heart rate (P<0.05). Univariate and multivariate test results were similar in the 357 asymptomatic patients and in the entire 411 subject cohort.

View this table: [in this window] [in a new window]   Table 4. Univariate Predictors of an Abnormal SPECT

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study is the first to describe the relationship between severity of coronary artery calcification detected by EBCT and the presence of stress-induced myocardial ischemia in a large cohort of predominantly asymptomatic subjects with risk factors for CAD development. The presence and extent of stress-induced myocardial ischemia detected by SPECT are known to predict subsequent outcome.^{3 4 5 6 7 8} Our results indicate that most subjects with coronary calcium do not have inducible ischemia but that the likelihood of ischemia increases with total CACS, particularly with scores 400. In fact, total CACS 400 identified a group in whom a large percentage of subjects (46%) had demonstrable ischemia. Conversely, only 6.6% of those with scores <400 had an ischemic defect size by SPECT, and virtually all (99.3%) were small. These observations suggest that CACS 400 could be used to improve the selection and use of more definitive and expensive tests such as SPECT for identifying individuals at high risk for cardiac events within the next year.

In our study, the best predictor of an abnormal SPECT was CACS. This result is consistent with previous studies demonstrating that the angiographic extent and severity of CAD are directly related to CACS severity^{11 12} and that angiographic stenosis severity best predicts an abnormal SPECT.^{2 16} Our findings emphasize that EBCT is more sensitive than either ETT or SPECT for detecting subclinical CAD in which aggressive risk factor modification is warranted and can further identify a subset of individuals at high risk for silent myocardial ischemia in whom additional diagnostic testing and treatment are advisable.

Identifying High-Risk Individuals With Ischemia
The presence and extent of scintigraphic ischemia predict short-term risk for cardiac events.^{3 4 5 6} Patients who have a normal or minimally abnormal SPECT have a <1%/y risk of death or myocardial infarction compared with a 5- to 10-fold-higher event rate with larger defects (15%).^{3 4 5 6} In our study, total CACS 400 defined a population at high risk for having scintigraphic ischemia. In fact, 15% of subjects with CACS 400 had large (15%) perfusion defects compared with <1% of those with lower scores. Thus, most cardiac events should occur in the small subset of subjects with high CACS. Indeed, a recent large clinical trial reported that asymptomatic subjects with CACS <400 had an exceedingly low (<0.5%) 1- to 2-year cardiac event rate, with virtually all events occurring in individuals with higher scores.²⁰

EBCT for Detection of Subclinical CAD
We specifically chose to compare SPECT and EBCT because of the well-recognized accuracy of SPECT in detecting CAD.^{2 16 17 18} However, most of our subjects (78%) with coronary calcium had a normal SPECT and would have been incorrectly labeled as not having coronary atherosclerosis. Likewise, only 4 (1.3%) with an abnormal EBCT had a high-risk Duke score. Our results support previous studies demonstrating that asymptomatic subjects with cardiac risk factors generally have normal ETT and perfusion scans.^{7 8 9} In the Lipid Research Clinics trial,⁹ only 8.3% of 3775 asymptomatic men with hyperlipidemia had exercise-induced ECG ischemia. In a study of middle-aged siblings of patients with premature CAD, the stress ECG was abnormal in only 10% and thallium imaging in 22%.⁷ In the Baltimore Longitudinal Study on Aging, few asymptomatic subjects had an abnormal stress ECG (16%) or thallium perfusion scan (14%).⁸ Although subjects who had abnormal results for both tests had a reduced event-free survival (52%), this was observed in only 5% of individuals screened; likewise, only 4.4% of our subjects had both abnormal ETT and perfusion imaging.

The low incidence of abnormal ETT or SPECT precludes their use as primary screening tests for early detection and treatment of CAD. The low incidence of ECG ischemia, particularly of a high-risk Duke score, in our study across a broad spectrum of CACS further emphasizes the poor diagnostic accuracy of ETT in identifying significant CAD in asymptomatic subjects.^{7 8 9} In fact, ETT and SPECT have both received a class III indication (ie, no justification for their use) for screening asymptomatic individuals.^{21 22} These tests, however, remain the cornerstone for evaluating risk in symptomatic patients with known or suspected CAD.^{1 2 3 4 5 6 19}

Detection of subclinical CAD seems desirable, particularly in view of recent primary prevention trials demonstrating that aggressive risk factor modification, including treatment of hyperlipidemia, reduces the incidence of subsequent cardiac events.^{9 23 24} Moreover, many asymptomatic individuals with subclinical CAD die suddenly²⁵ and would not have been identified with ETT or SPECT. In this regard, EBCT is appealing as a relatively low-cost, primary screening technique through which coronary atherosclerosis can be detected and potentially treated before the development of critical coronary artery stenosis and/or stress-induced myocardial ischemia.

Study Limitations
Subjects with CACS >100 were well represented in our study (29%), but <5% of those with lower scores had SPECT. It is unlikely, however, that studying a larger population with CACS 100 would have altered our results because these individuals generally have insignificant CAD by angiography.^{11 12 14} Another issue is whether our results vary with subject age. We observed similar correlations between SPECT and EBCT when individuals were dichotomized at 50 years of age; analysis by decade of life would require a larger sample size. Because of the small number of women who had SPECT, further study in this group is warranted.

Clinical Implications
In asymptomatic populations who have clinical characteristics similar to those of our cohort, 61 of every 100 individuals screened will have an abnormal EBCT, but only 10 will have CACS 400, warranting further evaluation with SPECT. Coronary angiography can then be appropriately reserved for the very few patients (1% to 2%) who have significant myocardial ischemia. Our study emphasizes the effectiveness of selectively combining SPECT with EBCT to identify individuals with silent myocardial ischemia who may require more intensive therapy with either anti-ischemic medications and/or coronary revascularization.

Conclusions
CACS severity measured by EBCT can identify a high-risk group with silent myocardial ischemia among an otherwise low-risk heterogeneous population with cardiac risk factors. Our results support the role of EBCT as a primary screening tool for identifying individuals with various degrees of subclinical CAD, particularly those at high risk for short-term events in whom aggressive diagnosis and therapy are advisable.

	Acknowledgments

 
We gratefully acknowledge the assistance of Maria E. Frias.

	Footnotes

 
Reprint requests to John J. Mahmarian, MD, 6550 Fannin St, SM-1246, Houston, TX 77030-2717.

Guest editor for this article was Bruce Brundage, MD, Bend Memorial Clinic, Bend, Ore.

Received May 25, 1999; revision received August 9, 1999; accepted August 26, 1999.

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				C.-D. Lee, D. R Jacobs Jr, P. J Schreiner, C. Iribarren, and A. Hankinson Abdominal obesity and coronary artery calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study Am. J. Clinical Nutrition, July 1, 2007; 86(1): 48 - 54. [Abstract] [Full Text] [PDF]

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				A. Rozanski, H. Gransar, N. D. Wong, L. J. Shaw, R. Miranda-Peats, D. Polk, S. W. Hayes, J. D. Friedman, and D. S. Berman Clinical Outcomes After Both Coronary Calcium Scanning and Exercise Myocardial Perfusion Scintigraphy J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1352 - 1361. [Abstract] [Full Text] [PDF]

				G. Ramakrishna, J. F. Breen, S. L. Mulvagh, R. B. McCully, and P. A. Pellikka Relationship Between Coronary Artery Calcification Detected by Electron-Beam Computed Tomography and Abnormal Stress Echocardiography: Association and Prognostic Implications J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2125 - 2131. [Abstract] [Full Text] [PDF]

				R. C. Johnson, J. A. Leopold, and J. Loscalzo Vascular Calcification: Pathobiological Mechanisms and Clinical Implications Circ. Res., November 10, 2006; 99(10): 1044 - 1059. [Abstract] [Full Text] [PDF]

				R. A. Vogel Coronary Artery Calcification and Myocardial Perfusion: Kissing Cousins or Distant Relatives? J. Am. Coll. Cardiol., September 5, 2006; 48(5): 1027 - 1028. [Full Text] [PDF]

				L. Wang, M. Jerosch-Herold, D. R. Jacobs Jr, E. Shahar, R. Detrano, A. R. Folsom, and for the MESA Study Investigators Coronary Artery Calcification and Myocardial Perfusion in Asymptomatic Adults: The MESA (Multi-Ethnic Study of Atherosclerosis) J. Am. Coll. Cardiol., September 5, 2006; 48(5): 1018 - 1026. [Abstract] [Full Text] [PDF]

				Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]

				Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]

				T. Yoshimura, E. Suzuki, K. Egawa, Y. Nishio, H. Maegawa, S. Morikawa, T. Inubushi, A. Hisatomi, K. Fujimoto, and A. Kashiwagi Low Blood Flow Estimates in Lower-Leg Arteries Predict Cardiovascular Events in Japanese Patients With Type 2 Diabetes With Normal Ankle-Brachial Indexes Diabetes Care, August 1, 2006; 29(8): 1884 - 1890. [Abstract] [Full Text] [PDF]

				D. S. Berman, R. Hachamovitch, L. J. Shaw, J. D. Friedman, S. W. Hayes, L. E.J. Thomson, D. S. Fieno, G. Germano, N. D. Wong, X. Kang, et al. Roles of Nuclear Cardiology, Cardiac Computed Tomography, and Cardiac Magnetic Resonance: Noninvasive Risk Stratification and a Conceptual Framework for the Selection of Noninvasive Imaging Tests in Patients with Known or Suspected Coronary Artery Disease J. Nucl. Med., July 1, 2006; 47(7): 1107 - 1118. [Abstract] [Full Text] [PDF]

				D. V. Anand, E. Lim, D. Hopkins, R. Corder, L. J. Shaw, P. Sharp, D. Lipkin, and A. Lahiri Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy Eur. Heart J., March 2, 2006; 27(6): 713 - 721. [Abstract] [Full Text] [PDF]

				T. Edvardsen, R. Detrano, B. D. Rosen, J. J. Carr, K. Liu, S. Lai, S. Shea, L. Pan, D. A. Bluemke, and J. A.C. Lima Coronary Artery Atherosclerosis Is Related to Reduced Regional Left Ventricular Function in Individuals Without History of Clinical Cardiovascular Disease: The Multiethnic Study of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 206 - 211. [Abstract] [Full Text] [PDF]

				P. Raggi, A. Bellasi, and C. Ratti Ischemia Imaging and Plaque Imaging in Diabetes: Complementary tools to improve cardiovascular risk management Diabetes Care, November 1, 2005; 28(11): 2787 - 2794. [Abstract] [Full Text] [PDF]

				E. Rzewuska-Lech, M. Jayachandran, L. A. Fitzpatrick, and V. M. Miller Differential effects of 17{beta}-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E105 - E112. [Abstract] [Full Text] [PDF]

				N. D. Wong, A. Rozanski, H. Gransar, R. Miranda-Peats, X. Kang, S. Hayes, L. Shaw, J. Friedman, D. Polk, and D. S. Berman Metabolic Syndrome and Diabetes Are Associated With an Increased Likelihood of Inducible Myocardial Ischemia Among Patients With Subclinical Atherosclerosis Diabetes Care, June 1, 2005; 28(6): 1445 - 1450. [Abstract] [Full Text] [PDF]

				S. Lai, J. A. C. Lima, H. Lai, D. Vlahov, D. Celentano, W. Tong, J. G. Bartlett, J. Margolick, and E. K. Fishman Human Immunodeficiency Virus 1 Infection, Cocaine, and Coronary Calcification Arch Intern Med, March 28, 2005; 165(6): 690 - 695. [Abstract] [Full Text] [PDF]

				M. F. Di Carli and R. Hachamovitch Should we screen for occult coronary artery disease among asymptomatic patients with diabetes? J. Am. Coll. Cardiol., January 4, 2005; 45(1): 50 - 53. [Abstract] [Full Text] [PDF]