Staging of Lung Cancer

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1 Coronary calcium score

2 Atherosclerosis Repeated inflammation and repair Clinical end points Related to arterial luminal stenosis Subclinical disease Arterial wall disease Progress without symptoms for decades Visualization Luminogram Detection of protruding lesion Intervention Component of vessel wall Detection of protruding and non-protruding lesion Tissue characterization

3 Atherosclerosis imaging Intimal/medial thickness by carotid US risk of future stroke Coronary artery calcium by EBT/MD CT risk of future cardiac event MRI Characterization of plaques Blood Blood flow quantification

4 How to do coronary artery calcium score (CACS) study?

5 EKG gating in EBT/MD CT Prospective EKG triggering Sequential multislice acquisition Identical reconstruction time for all 3 vessels Retrospective EKG gating Continuous Spiral Acquisition & Parallel ECG Recording Retrospective phase selection for image reconstruction LAD 60-70% of RR interval LCX 50% of RR interval RCA 40% of RR interval Kopp et al. Radiol 2001;221:683

6 Prospective ECG-Triggering & Sequential multi-slices Images z - Position Scan Feed Delay Scan R R R R Time

7 EBT vs. MD-CT Temporal resolution EBT; 33, 50, 100 msec MD CT; gantry rotation time X (360+40)/2 200 msec EBT; HR vs. MD CT; HR <65 Length of diastolic phase vs. HR

9 Measurement of CAC score Agatson method >130HU area 2 contiguous pixels density factor ( =1; 199=1; =2; 299=2; =3; 399=3; >400=4) Calcium volume method Linear interpolation to isotropic volume Agatston et al. JACC 90;34:777 All voxels (mm 3 ) >130HU Callister et al. Radiol 1998 Calcium mass method Pixel volume X attenuation value X ratio = total mineral content Ca equivalent (mg) Hong et al. Radiol 2002

10 Coronary artery calcium (CAC): Pathogenic significance & correlation Pathognomonic of intimal atherosclerosis No Monckeberg s calcific medial sclerosis in CA Ca in ashed specimen CAC (r=.97) Histologic plaque area CAC in each heart (r= ) and each artery (r= ).70) CAC total atherosclerotic plaque burden Poor correlation with CAC and a site-by by-site luminal stenosis (r=.07) Mautner et al. Radiol 94;192:619, Rumberger et al. Circul 95;92:2157 Sangiorgi et al. JACC 98;31:126

11 Histopathologic correlation CAC score 0 Absence of atherosclerosis Calcified plaque = 20% of total plaque burden Rumberger et al. Circul 95;92:2157

12 Coronary calcium Calcium is associated with coronary atherosclerotic disease activity. CA CA seen in all degrees of atherosclerosis From stage III (microscopic calcification) to VI All All subtypes of plaque coexist together by IVUS Similar Similar CA in stable and ruptured plaque CA CA in IRA > non-ira >1000 >1000 had >50% AMI or death over 3yrs Baumgart et al.jacc 97;30:57, Mascola et al. Am J Card 2002, Schmermund et al. Am J Card 2002, Wayhs et al. JACC 2002

13 CACS in general population Age Gender Risk factors for atherosclerosis DM hypertension hypercholesterolemia smoking (>10 cigarettes/day) precocious family history (M<55, F<65) obesity hypercholesterolemia (HDL <45mg/ml, LDL > 100mg/ml)

14 Coronary Calcium Score in American Prevalence of CAC mimic the incidence of CV atherosclerotic disease in men and women.

16 CAC score among various ethnic group

17 CAC score in Korean

18 Clinical Application

19 Cardiac events in aymptomatics N CACS cutoff Risk ratio Arad Detrano Raggi 632 Top quintile 15.4 Arad Kondos M;10.5, F;2.6

20 Annual event rate of CAOD in asymptomatics Guerci et al. AJC 97;79:128, Raggi et al. Am Heart J 01;141:375, Georgiou et al. JACC 01;38:105, Wayhs et al. JACC 02;39:225

21 FRI, ATP III & PROCAM RI vs. RI RI vs. CACS Achebach et al. Am J Cardiol 03;92:1471 FRI; Risk at one time point CACS; Risk accumulated Risk to be detected and measured

22 Risk factors for CACS & CAOD Identical for Age, Age, male gender, total/ldl cholesterol ratio, fibrinogen in large degree Hypertension in lesser degree Only for angio,, not CAC SmokingSmoking Schmermund et al. JACC 98;31:1267

23 Combine atherosclerotic imaging with risk factor assess AHA prevention V (1998) Greenland et al. Circ 00;101;E16 The test can be used as an adjunct to risk assessment based on through knowledgeable physician referral. ACC/AHA (2000) O Rourke et al. Rourke et al. Circul 00;102:126, Concerns cost effectiveness High NPV for short-term term events NCEP ATPIII (2002) Circ 02;106;3143 Risk assessment at first Selection of the group with cost effectiveness

24 Risk stratification in asymptomatics Prevention of CAOD Secondary prevention aggressive Rx in pts with established CAOD primary prevention Low risk; <6%/10yr, Retest in 5 yrs (35%) Intermediate risk; 6-20%/10yr 6 (40%) High risk; >20%/10yr (25%) Intensive Rx reserved for CAOD patients AHA prevention V conference

25 Prognostic value of RFs and CAC Shaw LJ et al. Radiol 2003;228;826

26 Annual rate of CHD in asymptomatics with intermediate risks Authors n age CACS Rate/yr Arad et al >80 th %tile 1.8% Detrano et al >67 th %tile 2.3% Raggi et al >75 th %tile 4.5% Arad et al. JACC 00;36:1253, Detrano et al. 99;99:2633, Raggi et al. Circ 00;101:850

27 New NCEP ATPIII guideline Measurement of coronary calcium is an option for advanced risk assessment in appropriately selected persons. Asymptomatics with intermediate risks Elderly In persons with multiple risk factors, high CACS (>75 th percentile for age and sex) denotes advanced coronary atherosclerosis and provides a rationale for intensified LDL- lowering therapy. Executive sum of 3 rd report of NECP. JAMA 01;285:2486

28 CACS; Preventive cardiology More likely to have cardiac event Early prevention is better than delayed treatment. Selection of asymptomatic persons who should be on drugs for lifetime Framingham risk index >20%/10yr intermediate FRI with CAC > 75 th percentile (>100 in women and <60yo men and >400 in >60yo men) Motivate life-style behavior changes Seeing is believing

30 Detection of silent ischemia in asymptomatics with high risks

31 CACS Indication in symptomatics Atypical Atypical chest pain Nonspecific + on TMT If CACS = 0 NPV of EBT is very high ( 99%)( and score 0 can virtually exclude CAOD, making the test an effective filter before invasive angiography. Budoff et al. Am J Cardiol 00;86;8

32 Conclusion; Coronary calcium score study Pathognomonic of atherosclerosis Total atherosclerotic burden Identify Identify CAD in preclinical stage Preventive cardiology risk assess cost-effectiveness in primary prevention modify modify natural history of atherosclerosis

33 Thank for your attention!

34 CACS in Korean Asymptomatic, middle-aged, /s prior CAOD Total Total 445 (M 260, F 185) Age Age 37-81(mean 57.5± 8.0) CACS CACS in average 72.1± Men 87.1 ± Women 51.1 ± Prevalence of CAC in average 45.4% Men 51.5% women 36.8%

35 CACS in Korean Risk Factors No. % MW(p) Overweight (BMI >25Kg/m 2 ) Smoking Hypertension (>140/90mmHg) Precocious family history HDL (<35mg/dl) DM (>140mg/dl fasting glucose) Total cholesterol (> 240mg/dl) MW; Mann-Whitney test

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