1. Coronary Calcium Scoring for Risk Stratification and Guidelines Matthew Budoff, MD, FACC, FAHA Professor of Medicine Director, Cardiac CT Harbor-UCLA Medical Center, Torrance, CA Name of company: GE - grant

2. NEW GUIDELINES

3. Measurement of CAC is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (10% to 20% 10-year risk. Measurement of CAC may be reasonable for cardiovascular risk assessment persons at low to intermediate risk (6% to 10% 10-year risk). In asymptomatic adults with diabetes, 40 years of age and older, measurement of CAC is reasonable for cardiovascular risk assessment. Recommendations for Calcium Scoring Methods I IIaIIbIII I IIaIIbIII I IIaIIbIII

4. l Computed tomography for coronary calcium should be considered for cardiovascular risk assessment in asymptomatic adults at moderate risk. IIa

5. Yeboah JAMA 2012 - MESA

6. CAC and CTA Hou JACC 2012

7. BIOMARKERS Wang NEJM 2006 10 biomarkers in 3209 participants attending a routine examination of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro–atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to- creatinine ratio.

8. NEJM CRP/Fibrinogen Oct 2012 l Net Reclassification with CRP 1.5%

9. BLAHA Lancet 2011

10. MESA – BLAHA Lancet 2011

11. Shemesh - Ungated Studies 8782 patients, 6 year f/u

12. 0 10 20 % 10-year risk ATPIII Score Risk Assessment CAC Score high risk Intermediate risk low risk Reclassification of ATP III Risk Categories Using CAC 51.5%28.8% 19.7% Scheme according to Wilson PWF et al JACC 41:1889 – 1906, 2003 with HNR data 62.9 % 23.1 % 14.1 %

13. Rotterdam Heart – JACC 2010 Addition of CRP did not improve C Statistic or Reclassification

14. Rotterdam – Annals 2012

15. CAC and CHF – Rotterdam JACC 2012 l 1897 Patients l 6.8 year follow up l CAC scores were associated with heart failure (p 0.001), with a hazard ratio of 4.1 l Net reclassification index 34.0%).

16. EISNER Randomized Controlled Trial Rozanski. Berman. Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research. JACC 2011;57:1622. 2137 middle-aged + risk factors without CVD 45-79y without CAD/CVD followed 4 years No ScanScan Clinical evaluation Questionnaire Risk factor consultation Clinical evaluation Questionnaire Risk factor consultation CAC scan Scan consultation

17. Does CAC scanning improve outcomes? ParametersCACS = 0CACS>400P Change in LDL- C -12 mg/dL-29 mg/dL<0.001 Change in SBP-4 mm Hg-9 mm Hg<0.001 Exercise32%47%0.03 New Lipid Rx19%65%<0.001 New BP Rx20%46%<0.001 New ASA Rx5%21%<0.001 Lipid Adherence80%88%0.04 Favorable change in RF, Rx with increasing CAC CACS may effectively triage care – evaluation, intensification of therapy – without increasing cost Rozanski. Berman. EISNER. JACC 2011;57:1622. CACS 0 = 631. CACS>400 = 109.

18. EISNER Study – Costs Compared to No Scan Group P<0.005 for both measures Rozanski JACC 2011

19. NICE GUIDELINES

21. NICE ALGORITHM

22. Grundy. Circulation 2008;117:569-573 “Imaging has at least 3 virtues” It individualizes risk assessment beyond use of age, which is a less reliable surrogate for atherosclerosis burden It provides an integrated assessment of the lifetime exposure to risk factors It identifies individuals who are susceptible to developing atherosclerosis beyond established risk factors

23. Once subclinical atherosclerosis is detected, intensity of drug therapy could be adjusted for plaque burden Grundy. Circulation 2008;117:569-573 “Imaging has at least 3 virtues”