1. Screening and Treatment of Coronary Artery Disease Matthew J. Budoff, MD, FACC Associate Professor of Medicine Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA DISCLOSURE INFORMATION: The following relationships exist related to this presentation:

2. Electron Beam Computerized Tomography Crystal-photodiodes Preamplifiers Source collimator Target ring Vacuum envelope Patient cross section 47cm scan field Target rings Source collimator Radiation shield Vacuum chamber Heart Detectors

5. CAC vs HISTOLOGY l High correlation of score (r=0.96) and area (r=0.95) with histomorphometry (p<0.0001) l “.. the amount of coronary calcium increases as the extent of atherosclerosis increases” Mautner GC et al: Radiology 1994;192:619-623

6. 20% 80% Total Coronary Artery Plaque and EBCT Coronary Calcium 80% PlaqueDetectable by IVUS, Pathology Lipid Rich Fibrotic Calcified 20% 80%

7. Calcium Score Total Plaque Burden Total Coronary Artery Plaque Burden and EBCT Coronary Calcium Score: defining the tip of the atherosclerotic iceberg Mild Plaque Severe Moderate

8. Framingham Risk in the Young l 222 patients with AMI (men < 55, women <65) l Only 25% qualified for pharmacotherapy based on 10-year risk prior to MI l Only 18% of women met criteria l Akosah – JACC 2003

9. Prediction of Cardiac Events in Asymptomatic Patients by EBT Pohle, Heart 2003:89:625-628 l 102 patients with AMI, age < 60 years l 95.1% had calcification present l Only 5.8% of controls had calcification present (p<0.0001) l Agatston >50% score – present in 87% l By extrapolation, this test may allow identification of 87-95% of the 650,000 patients whose first presentation is Myocardial infarction or cardiac death

10. Refining Framingham Risk Score EBT derived “Arterial Age” a man is as old as his coronaries… Syndenham 1689 EBT derived “Arterial Age” a man is as old as his coronaries… Syndenham 1689

11. EBCT CORONARY CALCIUM SCORES AS FUNCTION OF AGE AND GENDER MALES 0 100 200 300 400 500 600 700 800 900 1000 30-3940-4950-5960-6970+ 10th 25th 50th 75th 90th

12. EBCT CORONARY CALCIUM SCORES AS FUNCTION OF AGE AND GENDER FEMALES A

13. Negative Predictive Power of EBT l 1764 persons underwent EBT and angiogram l Sensitivity for Obstruction (any calcium) 99.4% in men, 100% in women l Negative predictive power > 99% l Can be used as a ‘filter’ prior to angiography to help avoid negative angiograms Haberl et al. JACC Feb 2001

14. EBCT “Screening” in the Emergency Room: Results in the Mayo Clinic “chest pain unit” NPV for “Significant” CAD of 100% 50% women, 98% Caucasian All events occurred in those with CAC Annals of Em Med, 1999

15. CARDIOMYOPATHY l Evaluate Cardiomyopathy of Unknown Etiology using EBT l The sensitivity of coronary calcium depicting an ischemic cardiomyopathy was 99% (score >0 = presumed ischemic CM) 1 l Better than echocardiography or stress testing at distinguishing ischemic from dilated CM 2 1 Budoff et al. JACC 1999 2Le T. Clin Card 2000

16. Sensitivity of Calcium for Future Cardiovascular Events

17. Rusty Pipe Model of Atherosclerosis

18. NormalvesselMinimalCAD Progression Artery can compensate for up to 40% plaque volume (lumen size remains constant) Artery at maximumexpansion: lumen narrows SevereCADModerateCAD Glagov S et al, N Engl J Med, 1987. Glagov Hypothesis: Coronary Remodeling

19. NormalvesselMinimalCAD Progression Artery can compensate for up to 40% plaque volume (lumen size remains constant) Artery at maximumexpansion: lumen narrows SevereCADModerateCAD Glagov S et al, N Engl J Med, 1987. Glagov Hypothesis: Coronary Remodeling

20. NormalvesselMinimalCAD Progression Artery can compensate for up to 40% plaque volume (lumen size remains constant) Artery at maximumexpansion: lumen narrows SevereCADModerateCAD Glagov S et al, N Engl J Med, 1987. Glagov Hypothesis: Coronary Remodeling

21. False Negative Coronary Angiography Diffuse Atherosclerosis despite negative angiogram Images supplied by Steven E. Nissen, MD, Cleveland Clinic.

22. Asymptomatic Persons Nuclear Imaging Hu, Circulation 2000

23. Historical Development of a Coronary Artery Plaque This process, in various stages of development, can be seen in many areas of the coronary artery system, consistent with the “diffuse” nature of coronary artery disease EBCT “positive” for coronary calcium

26. The challenge in diagnosis of coronary heart disease “The majority of people destined to die suddenly will not have a positive exercise test. The likely reason that they will die suddenly is that only a mild, non-flow -limiting coronary plaque will have been present before the sudden development of an occlusive thrombus.” - Stephen Epstein - Stephen Epstein New England Medical Journal 1989

27. RR of MI/SCD: EBT Score and hs-CRP Low hs-CRP High hs-CRP Park et al. Circ. 2002;106-2073-2077

28. CAC by EBT and Cardiac Events n=64 99% n=1 1% 696 pts. 53+11 yrs 50% males 2.7 year f/u Raggi et al Circ 2/00 65 Cardiac Events (Cardiac Death, MI, Revasc) Event Rate: 6%/yr <.1%/year

29. Event Rates Based upon Scores Raggi, AHJ 2001

30. Figure 1. Probability of survival free of events in 98 consecutive asymptomatic subjects with calcium score >1,000 on a screening electron beam tomography scan. Wayhs R, Zelinger A, Raggi P, J Am Coll. Card., Vol 39: pp 225-230, 2002 High Coronary Artery Calcium Scores Pose an Extremely Elevated Risk for Hard Events

31. Relative Risk Of Future Cardiac Event using EBT Raggi Wong Detrano

32. Prediction of Cardiac Events in Asymptomatic Patients by EBT Kondos et al, Circulation 2003;107:2571-2176 5635 asymptomatic, low to intermediate risk patients, 37+12 m f/u Cardiac events: MI, SCD, revascularization, age 30-76, avg 51+9 yrs. 1.00.751.251.503.030.0 Age: 1.04-1.07 1.051.39 Smoking: 1.04-1.87 0.87 Elevated TC: 0.65-1.07 1.98 DM: 1.19-3.28 1.33 HTN: 0.98-1.81 10.46 Presence of CAC: 3.85-28.4 RelativeRisk

33. Prediction of Cardiac Events in Asymptomatic Patients by EBT The St. Francis Heart Study, ACC 2003 SFHS 3 Baseline EBT Calcium Score Annual Event Rate (%) Calcium Score >100 vs <100 Relative Risk 9.5 Any Event 10.7 Cor. Event 9.9 MI/ SCD

36. Relative Risk DMSmokeHTN<10 10-100 101-400 401-1000 >1000 EBT Coronary Calcium Score All Cause Mortality [NDR] n = 10,377 asymptomatic men and women f/u = 5.0+3.5 yrs. Shaw, Raggi et al In Press, Radiology 2003 EBT found to be independent and incremental to risk factors All Cause Mortality in Patients Without Known CAD

37. 5 Year Mortality

38. EBT 5 year All-Cause Mortality

39. Risk Stratification – Shaw et al.

40. Rationale for Use of CAC in Different Populations Risk Category PopulationNumber Shifted Number Needed to Scan Low35%2%50 Intermediate40%73%1.3 High25%16%7

41. Asymptomatic Patient Algorithm for Intermediate Risk Patients Greenland P, et al. Circulation Oct 9, 2001

42. “measurement of coronary calcium is an option for advanced risk assessment. High coronary calcium scores (e.g., >75 th percentile for age and sex) denotes advanced atherosclerosis and provides rationale for intensified LDL-lowering therapy.” NCEP ATP-III : Noninvasive Testing

43. Prevention V Guidelines l Used a score >80 by EBT to implement aggressive drug treatment in Framingham intermediate risk patients l In patients with a zero score, “one would not be justified to intervene with costly lipid lowering drugs at this time”

44. Percent Volume Change vs LDL +120% 0 –80% 60120200 LDL (mg/dL) TreatedUntreatedSuboptimal Therapy (LDL >120 mg/dl) Callister et al. N Engl J Med. 1998;339:1972-1978. CAC Score Change

45. Achenbach S, Circulation, Vol 106: Aug. 27, 2002 Rates of Progression of CAC 25% 8.8% P<0.0001 n=66 Before StatinAfter Statin

46. Achenbach S, Circulation, Vol 106: Aug. 27, 2002 32 Patients who achieved LDL <100 Mg/dL 27% -3.4% P=0.0001 n=32 Before StatinAfter Statin

47. Annual Event Rate with Progression Annual CAC Score Change Raggi, Budoff AJC 2003 13X Risk

48. Progression and Medical Intervention

49. COMPLIANCE l “Willpower lasts about two weeks…. And is usually soluble in alcohol” Mark Twain/Sam Clemens

50. ~50% of patients discontinue lipid-lowering therapy within 1 year. ~75% of patients discontinue lipid-lowering therapy within 2 years. Compliance and Lipid-Lowering Therapy Roberts, Am. J. Cardiol. 78:1996:377-378.

52. Percentage of individuals maintaining Statin therapy at 3.6 years according to various levels of baseline CAC

53. Odds ratio of maintaining statin therapy with various levels of baseline CAC 2.4 5.1 1.1 4.2 1.9 9.1 9.3 3.0 28.9

54. 5 USES OF EBT l Use a calcium score to screen patients with moderate (intermediate) Framingham risk n Positive EBT scans indicate incremental risk n Alters therapeutic goal (LDL, BP, etc) l Identify patients who do not need further cardiac evaluation (scores of zero) l Consider serial imaging as ongoing management tool (progression) l Improve compliance l Non-invasive Angiography

55. EBT Coronary Calcium