1. Predictive Value of Coronary Calcium Scoring Matthew Budoff, MD, FACC, FAHA Associate Professor of Medicine UCLA School of Medicine Director, Cardiac CT Harbor-UCLA Medical Center, Torrance, CA Conflict of Interest: Speakers Bureau General Electric

3. Prevalence of Conventional Risk Factors in Patients with Coronary Heart Disease (N = 87,869)

4. Time 0 1 22x A.S. x Coronary atherosclerotic burden – No one is born with atherosclerosis

5. Time 0 1 22x A.S. x Coronary atherosclerotic burden – There is a gradual, silent build up over time xx x x x x x x x

6. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – Finally, acute event occurs xx x x x x x x x x x

8. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – Sx onset -- Permanent damage xx x x x x x x x x x Time 1 1/3 - Angina 1/3 - Acute MI 1/3 - Sudden Death

9. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – xx x x x x x x x x x 1 st Event Realistic Goal – DELAY PROGRESSION x x x x x xxxxxxx x x x x x x x x x x x x x x x

10. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – xx x x x x x x x x x 1 st Event Prevention- Primary vs. Secondary x x x x x xxxxxxx x x x x x x x x x x x x x x x CARDIOLOGISTS

11. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – xx x x x x x x x x x 1 st Event Prevention- Primary vs. Secondary x x x x x xxxxxxx x x x x x x x x x x x x x x x PRIMARY CARE

12. Time 0 1 2 2x A.S. x Coronary atherosclerotic burden – xx x x x x x x x x x 1 st Event Concept -- EARLY 2 ry PREVENTION x x x x x xxxxxxx x x x x x x x x x x x x x x x The Problem begins HERE NOT HERE

13. Potential Prognostic Potential of Cardiac CT l Use a calcium score to screen patients with moderate (intermediate) Framingham risk n Positive CAC scans indicate incremental risk n Alters therapeutic goal (LDL, BP, etc) l Identify patients who do not need further cardiac medication (scores of zero) l Consider serial imaging as ongoing management tool (progression)

14. 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

15. 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 Radiology 2003 EBT found to be independent and incremental to risk factors All Cause Mortality in Patients Without Known CAD

16. EBT 5 year All-Cause Mortality – Shaw et al

17. 0.002.004.006.008.0010.0012.00 Time to Follow-up (Years) 0.75 0.80 0.85 0.90 0.95 1.00 0.001.002.003.004.005.00 Time to Follow-up (Years) 0.75 0.80 0.85 0.90 0.95 1.00 Near- and Long-Term Survival from 2 Cohorts – over 35,000 patients n=10,377 n=25,257 99.4% 97.8% 95.2% 90.4% 81.8% 99.4% 97.8% 94.5% 93.0% 76.9%  2 =1503, p<0.0001, interaction p<o.0001 CAC Score (5 Yr Mortality = 1.2%) (12-Yr Mortality = 2.1%)Difference 0-10 99.4% 99.4% 0.0% 11-100 97.8% 97.8% 0.0% 101-400 95.2% 94.5% 0.7% 401-1,000 90.4% 93.0% 0.6% >1,000 81.8% 76.9% 4.9%

18. Cooper Clinic Study - 10,782 Patients: 3.5 year follow-up Adjusted age, history of diabetes, hypertension, elevated cholesterol, over weight 44.3 (22-87) 2.9 (1.2-6.7) 5.2 (2.4-11) 13.4 (6.7-26.5) Ref All CHD (n=278) Nonfatal MI & CHD Death 2.7 (0.8-9.3) 6.0 (2.1-17) 9.7 (3.6-26) 21.1 (7.8-57) Ref

19. Taylor et al – PACC Study – JACC 2005 l 2000 patients, mean age 43 l Coronary calcium was associated with an 11.8-fold increased risk for incident coronary heart disease (CHD) (p 0.002) in a Cox model controlling for the Framingham risk score. l In young, asymptomatic men, the presence of coronary artery calcification provides substantial, cost-effective, independent prognostic value in predicting incident CHD that is incremental to measured coronary risk factors.

20. Calcium Versus Framingham

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

22. AHA – Circulation 2005 Given the evolving literature since the last ACC/AHA Expert Consensus statement (2000), current data indicate that CAD risk stratification is possible with CAC measures. Specifically, low CAC scores are associated with a low adverse event risk, and high CAC scores are associated with a worse event-free survival. This recommendation to measure atherosclerosis burden, in clinically selected intermediate–CAD risk patients (eg, those with a 10% to 20% Framingham 10- year risk estimate) to refine clinical risk prediction and to select patients for altered targets for lipid-lowering therapies.

23. RAGGI - ATVB

24. Arad et al. JACC 2005 l In the largest study reported to date, multiple logistic regression, demonstrated only age (p 0.03), male gender (p 0.04), LDL cholesterol (p 0.01), HDL cholesterol (p 0.04), and two-year change in calcium score (p 0.0001) were significantly associated with subsequent CAD events. l Thus, increasing calcium scores were most strongly related to coronary events. l NOT PREDICTIVE: Baseline CAC, CRP

25. Potential Uses of Cardiac CT 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

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

28. EBT Coronary Calcium