Background. Stages. we detect these easily? New technology: The CT scanner, Example: calcium in peripheral vascular disease.

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1 Coronary Calcium Background Ahtherosclerosis: Maturation of a plaque into symptomatic disease Coronary Artery disease Fatty Streak: Autopsy, seen in autopsy Occurs very early, 0s, late teens Seen almost ubiquitously in industrialized children over age 0 CHRIS ROWAN RENOWN INSTITUTE FOR HEART AND VASCULAR HEALTH Stages What is the Calcium? Early Atherosclerosis: can we detect these easily? The presence of early calcium in an atheroma X-rays penetrate soft tissue with ease Cannot penetrate substance that is very dense Metal bone Calcium deposits Example: calcium in peripheral vascular disease New technology: The CT scanner, 97

2 Coronary Calcium Introduction of ECG gating Cardiac CTA Introduced in 972 Early CT scans did not have ability to ECG-Gate or freeze the image during the cardiac cycle Did not have the temporal resolution to visualize coronary arteries Only calcifications in the very proximal coronary segments could be qualitatively appreciated Mostly blurred With advances in electronics, it became possible to only take pictures at a specified time point of the ECG Shooting at peak systolic or peak diastolic leads to a frozen image of the heart that is reconstructed to cover the entire heart EBCT vs. Computer Tomography EBCT has superior temporal resolution over CT Electron beam or super fast CT Never caught on commercially ECG Gating ECG Gated Cardiac CT New Frozen Images Units of Calcium A complete 3D reconstruction of the heart could be done The Volume of calcium could be quantified Some calcium was brighter than other segments Adjustments were made Agatston unit Essentially the weighted volume of calcium present in a persons coronary arteries Weighted plaque density for HU of for HU for for > 400 Multiplied by the volume in mm^2 Assuming a 3 mm slice thickness Add up all the values for a total score

3 Coronary Calcium: Basics Total Coronary Artery Plaque and EBCT Coronary Calcium Presence of calcium is pathognomonic for atherosclerosis The total CAC score represents a measurement of total plaque burden Represents a matured or healed plaque Represents the mature stage of atherosclerotic plaque formation Total calcium give a burden of disease score 20% 80% Calcified 20% Fibrotic Plaque Detectable by IVUS, Pathology 80% 80% Lipid Rich Coronary Calcium Score So now what? What does this total calcium score mean? Review some of the data for coronary calcium scoring and what it predicts. All Cause Mortality in Patients Without Known CAD All Cause Mortality [NDR] n = 0,377 asymptomatic men and women f/u = yrs. Ca found to be independent and incremental to risk factors DM Smoke HTN < > Shaw, Raggi et al Radiology 2003 EBT Coronary Calcium Score Prediction of Cardiac Events in The St. Francis Heart Study, JACC 2005 St. Francis Heart Study Annual Event Rate (%) Relative Risk Calcium Score >00 vs <00 Any Event 0.7 Cor. Event MI/ SCD Calcium score predicted CAD events independently of standard risk factors and CRP (p=0.004) Note: more predictive than CRP Superior to Framingham Risk Index Area under ROC curve 0.79 vs p = Enhanced stratification of those falling into the Framingham categories of low, intermediate and high risk p > > 0 > 00 > 200 > 600 Baseline EBT Calcium Score SFHS 3 All Cause Mortality and CAC Scores: Long Term Prognosis in 25,253 patients Cooper Clinic Study - 0,782 Patients: 3.5 year follow-up Nonfatal MI & CHD Death (n=,044) -0 (n=3,567) -00 (n=5,032) Cumulative Survival (n=2,66) (n=56) (n=955) (n=54) Adjusted Odds Ratio Ref 2.7 ( ) 6.0 (2.-7) 9.7 (3.6-26) 2. (7.8-57) 0.70,000+ (n=964) 0 None > Time to Follow-up (Years) Budoff, et al. JACC 2007; 49: Adjusted age, history of diabetes, hypertension, elevated cholesterol, over weight

4 MESA Study 6,84 Patients: 3.5 year follow-up 50 Nonfatal MI & CHD Death What about other tests? 40 C-reactive protein Framingham Risk scores Hazard Ratio Ref 4.47 (2.45,8.3) 0.26 (5.62,8.7) 4.3 (7.9,25.22) Intima media thickness Ankle brachial index Brachial mediated flow dilation 0 None >300 Fully adjusted Detrano et al NEJM Yeboah JAMA MESA BIOMARKERS Wang NEJM 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, and homocysteine; and the urinary albumin-to-creatinine ratio. What if my score of 0 Warranty of a CAC Score of 0 What is the warranty for a calcium score of 0. 6,944 (42%) CAC=0 48 deaths 99.6% 99.3% Ketlogetswe AHA 200 Comparison to JUPITER BLAHA Lancet 20 JUPITER did not get coronary calcium scores LDL < 30 CRP > 2 MESA obtained coronary calcium scores on all participants Would further risk stratification by calcium score in the Jupiter patients of MESA change risk prediction Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Subset of Jupiter

5 BLAHA Lancet 20 by CRP Stratified by CRP Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Subset of Jupiter MESA BLAHA Lancet 20 What about my Diabetic Patients? Anand EHJ Diabetics CAC and FRS in uncomplicated Type 2 diabetes 50 asymptomatic type 2 diabetic subjects Mean F/U=2.3 yrs No event observed with CAC=0 UKPDS = UK Prospective Diabetes Score Anand DV et al, Eur Heart J. 2006; 27(6):73-2. How does this change my clinical management? Rotterdam Heart Study JACC 200 Prospective observation study 2,028 asymptomatic patients followed over median of 9.2 years Framingham Risk Scores performed for all patients Based on hard events, risk was reclassified based on Ca score

6 Rotterdam Heart JACC 200 CAC and CHF Rotterdam JACC 202 Addition of CRP did not improve C Statistic or Reclassification 897 Patients 6.8 year follow up CAC scores were associated with heart failure (p 0.00), with a hazard ratio of 4. Net reclassification index 34.0%. Rotterdam Annals 202 EISNER Randomized Controlled Trial 2,37 middle aged + risk factors without CVD 45-79y without CAD/CVD followed 4 years No Scan Clinical evaluation Questionnaire Risk factor consultation Scan Clinical evaluation Questionnaire Risk factor consultation CAC scan Scan consultation Rozanski. Berman. Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research. JACC 20;57:622. EISNER Study Costs Compared to No Scan Group EISNER Study CACS may effectively triage care evaluation, intensification of therapy without increasing cost Compared with the no scan group, the scan group showed a net favorable change in systolic blood pressure (p 0.02), low density lipoprotein cholesterol (p 0.04), and waist circumference (p 0.0), and tendency to weight loss among overweight subjects (p 0.07), and improvement of FRS compared to no scan group P<0.005 for both measures Rozanski JACC 20 Does CAC scanning improve outcomes? Favorable change in RF, Rx with increasing CAC Parameters CACS = 0 CACS>400 P Change in LDL- -2 mg/dl -29 mg/dl <0.00 C Change in SBP -4 mm Hg -9 mm Hg <0.00 Exercise 32% 47% 0.03 New Lipid Rx 9% 65% <0.00 New BP Rx 20% 46% <0.00 New ASA Rx 5% 2% <0.00 Lipid Adherence 80% 88% 0.04 Rozanski. Berman. EISNER. JACC 20;57:622. CACS 0 = 63. CACS>400 = 09. ST FRANCIS RANDOMIZED TRIAL Randomized Double Blind Placebo Controlled Trial of Atorvastatin in the Prevention of Cardiovascular Events Among Individuals With Elevated CAC Score No Prior CVD Men, Women years CAC >80% of age-gender Atorvastatin 20 mg (N=490) Placebo (N=55) Arad Y et al. J Am Coll Cardiol 2005: 46: MI Stroke CVD Death CABG/PTCA Mean duration of treatment was 4.3 years. Treatment with atorvastatin reduced clinical endpoints by 30% (6.9% vs. 9.9%), and MI/ Death by 44% (NNT 30) Event rates were more significantly reduced in participants with baseline calcium score >400 (8.7% vs. 5.0%, p=0.046 [42% reduction]). (NNT 6)

7 Progression of CAC Predicts All-Cause Mortality 4,609 consecutive asymptomatic patients Interscan time 3. yrs; 288 deaths After adjusting for baseline score, age, sex, and time between scans: Budoff JACC Imag 200 4,609 consecutive asymptomatic individuals >5% yearly increase HR: 3.0 Budoff. JACC Img 200;3: In nonprogressors In progressors Budoff Progression MESA JACC 203 Can this change my patients behavior? People worry about risk of CVD. Not many understand risk and risk reduction People understand that they have a disease! How do they respond when you tell them, You have coronary artery disease? Odds ratio of maintaining statin therapy with various levels of baseline CAC (3.6 yr f/u) Kalia et al Orakzai, Budoff et al. AJC Improving Adherence Taylor et al. JACC 2008 So what is the role for coronary calcium? Scenario: 48 y/o presents with no symptoms but concerned about risk factors. Every male on his fathers side had an MI prior to age 55. He has hypertension controlled on lisinopril 0 daily, total cholesterol of 89, LDL 28 and has never smoked. By Framingham, his 0 year risk is 4%.

8 Total Calcium score reported as 430. What now? Framingham score of 4% vs. CAC of Other patient scenario What about the new lipid guidelines? 42 y/o African American male with HLD, total cholesterol of 282, LDL 90. Ca score of 08 Ca score places him at the 97% for age! Should we get more aggressive with his lipids? ASCVD risk calculator says a 0 year risk is 3.8% and does not qualify for a statin. His Ca score places him above the 0% 0 year risk? What to do? Stay tuned. Take home points Or search for mesa risk calculator The extent of CAD burden, rather than the severity of stenosis, is the most important predictor of acute MI or sudden cardiac death (Circ 96:46-9.) Stress Testing only identifies patients with advanced CAD with now flow limiting stenosis. (Circ, 92: ) Prognosis is more closely tied to plaque burden and stability rather than to degree of stenosis Most patients get tertiary prevention following catheterization or if they are lucky, secondary. Calcium scoring provides a unique insight into a patients risk prediction. Calcium score says if they have the disease and how much! NEW GUIDELINES Recommendations for Calcium Scoring Methods I IIa IIb III Measurement of CAC is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (0% to 20% 0-year risk. I IIa IIb III Measurement of CAC may be reasonable for cardiovascular risk assessment persons at low to intermediate risk (6% to 0% 0-year risk). I IIa IIb III In asymptomatic adults with diabetes, 40 years of age and older, measurement of CAC is reasonable for cardiovascular risk assessment.

9 Computed tomography for coronary calcium should be considered for cardiovascular risk assessment in asymptomatic adults at moderate risk. IIa Thank you!