Coronary Artery Calcification

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1 Coronary Artery Calcification Julianna M. Czum, MD OBJECTIVES CORONARY ARTERY CALCIFICATION Julianna M. Czum, MD Dartmouth-Hitchcock Medical Center 1. To review the clinical significance of coronary heart disease and concepts of coronary atherosclerosis pathophysiology 2. To describe coronary calcium scoring methodology and interpretation 3. To discuss the clinical implications of accrued knowledge, published practice guidelines, and recent research results and their potential impact upon radiologists Coronary Heart Disease in the U.S. Coronary Heart Disease in the U.S. 1 out of 6 deaths in estimates: 785,000 new coronary attacks and 470,00 recurrent coronary attacks New coronary event: every 25 sec Someone dies from a coronary event: every minute 138,000 coronary deaths within 1 hr of symptom onset Estimated 195,000 silent first MIs/year Percentage breakdown of deaths due to CVD in U.S Lloyd-Jones D, et al. Heart and Stroke Statistics 2010 Update: A Report from the American Heart Association. Circulation 2010:121:e1-e170. Coronary Heart Disease in the U.S. Between , 35.9% decrease in coronary heart disease mortality Based on data, decrease attributable to: evidence-based medical therapies: 47% modification of risk factors (lifestyle and environmental): 44% Lloyd-Jones D, et al. Heart and Stroke Statistics 2010 Update: A Report from the American Heart Association. Circulation 2010:121:e1-e170. Lloyd-Jones D, et al. Heart and Stroke Statistics 2010 Update: A Report from the American Heart Association. Circulation 2010:121:e1-e170. Pathophysiology of Coronary Atherosclerosis Extracellular fatty deposits, inflammation, lipid-laden macrophages, smooth muscle cells, scar tissue build up in arterial walls Active calcium hydroxyapatite deposition Disruption of fibrous cap and exposure of plaque components intense thrombogenic reaction of circulating blood Hematoma can organize & calcify Repeated episodes fixed stenosis Highly variable plaque deposition and progression of occlusive disease. Naghavi M, et al. Circulation 2003; 108:

2 Total Coronary Artery Burden: CAC is the tip of the atherosclerotic iceberg Total Coronary Artery Burden: CAC is the tip of the atherosclerotic iceberg Calcified plaque volume is approximately 1/5 that of associated noncalcified plaque. CAC versus atherosclerotic burden: a linear, but not 1-to-1 relationship. Rumberger et al. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study. Circulation 1995; 92: Vulnerable plaque versus vulnerable patient Vulnerable Plaque = plaques prone to thrombosis or high probability of rapid progression, i.e. becoming culprit plaques (responsible for occlusion and death) Vulnerable Blood = prone to thrombosis Vulnerable Myocardium = ischemic with chronic damage, or non-ischemic causes; prone to life-threatening arrhythmia Naghavi M, et al. Circulation 2003; 108: Vulnerable plaque versus vulnerable patient CAC cannot identify vulnerable plaque Concept of pan-coronary vulnerability CAC may identify the vulnerable patient Naghavi M, et al. Circulation 2003; 108: Vulnerable plaque versus vulnerable patient Naghavi M, et al. Circulation 2003; 108: Significance of Coronary Calcification A direct relationship exists between presence and extent of coronary arterial mural calcification and severity of coronary atherosclerosis Repeatedly confirmed in autopsy studies Not exploited for patient evaluation for potential coronary artery disease Baron MG. Radiology 1994; 192:613-4.

3 Agatston score Agatston score 2-4 contiguous pixels attenuation of > 130 HU = calcium 3 contiguous pixels: 1.03mm 2 with 30 cm FOV and 512 x 512 matrix Area of calcified plaque x non-linear weighting factor based on peak density of the plaque: Agatston calcium score = (area x cofactor) Attenuation Weighting factor HU HU HU 3 >400 HU 4 Limitations: Partial volume effects Limited interscan reproducibility Motion-related artifacts Interpretation of Agatston CAC Scores: Absolute Values Interpretation of Agatston CAC Scores: Age and Gender Percentiles* Score Interpretation 0 No identifiable atherosclerotic plaque 1-10 Minimal atherosclerotic plaque burden Mild atherosclerotic plaque burden Moderate atherosclerotic plaque burden >400 Severe atherosclerotic plaque burden * Percentile rankings in 19,200 asymptomatic patients from University of Illinois self-referral database. Volume score Absolute CAC mass Improved inter-scan reproducibility Compared to Agatston score: Less susceptible to partial volume effects Allows quantification independent from section thickness or image overlap Volume = (area x increment) Limitation: lack of reference data for large populations Improved reliability of Ca measurement: independent of differences in CT systems & scanning protocols if calibrated with external standard or phantom Calcium mass proportional to mean CT number of a calcified plaque multiplied by lesion volume Mass = (calibration factor x CT Ca x volume) Reported as mg of calcium hydroxyapatite Limitation: lack of reference data for large populations 463

4 Coronary Calcium Coverage Score (CCCS): from MESA Coronary Calcium Coverage Score (CCS): from MESA Brown ER, et al. Radiology 2008; 247: Brown ER, et al. Radiology 2008; 247: Budoff, et al. JACC 2007;49: All Cause Mortality and CAC Scores: Long Term Prognosis in 25,253 patients (n=11,044) 1-10 (n=3,567) (n=5,032) (n=2,616) (n=561) (n=955) (n=514) 1,000+ (n=964) Multiethnic Study of Atherosclerosis (MESA) Prospective randomized cohort; 10-year NHLBI study begun in 2000 Detrano R, et al. NEJM 2008; 358: See also: McClelland RL, et al. Circulation 2006; 113:30-37 and Brown ER, et al Radiology 2008; 247: Multiethnic Study of Atherosclerosis (MESA) CACS Utility Above & Beyond Various Risk Factor Based Risk Algorithms 10-fold risk for calcium score > 300 Doubling of calcium score: 15 40% increase of coronary event risk Detrano R, et al. NEJM 2008; 358: Becker D et al, American Heart Journal

5 Adjusted odds ratios for CHD events CAC The presence of CAC (Agatston score >0 ) indicates that at least some atherosclerotic plaque is present. Clinically significant calcium, often an indication for more aggressive risk factor management, is often defined by a score >= 100 or a score >=75 th %ile for one s age and sex/gender. Pletcher MJ, et al. Arch Inter Med 2004; 164: (Systematic Review and Meta-Analysis) A score >=400 can be an indication for further diagnostic evaluation for coronary artery disease (e.g. exercise testing or myocardial perfusion imaging) Lloyd-Jones D, et al. Heart and Stroke Statistics 2010 Update: A Report from the American Heart Association. Circulation 2010:121:e1-e170. Screening for Heart Attack Prevention and Education (SHAPE) Task Force Guidelines CAC: implications for preventive measures Using traditional, non-imaging based risk stratification, e.g. Framingham: Apply a less aggressive primary prevention model for asymptomatic patients Apply a post-event secondary prevention model, i.e. based on clinical presentation, not plaque burden CAC: implications for preventive measures Early Identification of Subclinical Atherosclerosis by Non-invasive Imaging Research (EISNER) Asymptomatic patient post-cac screening: preventive treatment depends on calcium score, i.e. a marker of atherosclerotic plaque burden score = 0: no demonstrable atherosclerosis follow primary prevention guidelines score > 0: atherosclerosis present follow secondary prevention standards Randomized; 4 year follow-up for CVD death or MI Compared downstream cost differential of CAC vs FRS CAC scanning is associated with a marked differential in downstream frequency of medical tests and costs: very low frequency of testing and invasive procedures among a large percentage of subjects with low CAC scores selectively concentrated testing and procedures among a small number of subjects with CAC scores of more than 400. Shaw LJ, et al. J Am Coll Cardiol

6 Conclusions CAC is a marker of subclinical coronary atherosclerotic plaque burden in asymptomatic patients CAC is NOT a surrogate for clinical risk stratification schemes CAC for incremental risk prediction for intermediate (10-20% 10- year) risk of coronary events Reclassifying to higher risk status: alters therapeutic goal (LDL, BP, etc) NOT for reclassifying to lower risk status, even with calcium score =0 Score = 0: do not need further evaluation Screening for CAC is NOT recommended for lower-risk general population screening or for persons with pre-existing heart disease, diabetes mellitus, or other high-risk conditions Naghavi M, et al. Circulation 2003; 108: What may increase acceptance and utilization of CAC by the patients and the general medical community? 1. Insurance coverage of coronary calcium scoring: CMS 2010 Category 1 CPT code Publish practice guidelines in major medical journals: Circulation Easy access to free on-line evidence-based tools that calculate adjustments to conventional pre-cac 10-year risk estimates and generate post-test estimate for individual patients 2010 Practice Guidelines Measurement of CAC is reasonable for CV risk assessment in asymptomatic adults at intermediate risk (10-20% 10-year risk) Measurement of CAC may be reasonable for CV risk assessment in persons at low-to-intermediate risk (10-20% 10-year risk) Persons at low risk (<6% 10-year risk) should not undergo CAC measurement for CV risk assessment Greenland P, et al ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults. Circulation p.29 MESA public website

7 Framingham algorithm for hard CHD * events Framingham algorithm for hard CHD * events * Myocardial infarction and cardiac death from the National Cholesterol Education Program website: * Myocardial infarction and cardiac death from the National Cholesterol Education Program website: Downloadable spreadsheet Another example (Open Access Publishing site); see: Pletcher MJ, et al. Heart Views 2004;5: Pletcher MJ, et al. Arch Int Med 2004;164: Systematic review and meta-analysis (Open Access Publishing site); see: Pletcher MJ, et al. Heart Views 2004;5: Pletcher MJ, et al. Arch Int Med 2004;164: Systematic review and meta-analysis Patient Motivation: effect of visualization of CAC on lifestyle behavioral changes Why is this important to my practice? Orakzai, Budoff AJC 2008: 101:

8 Significance of Coronary Calcification CT is being increasingly used to evaluate coronary artery disease in the hope of detecting early atherosclerotic disease before cardiac events occur. Consequently, it is imperative for physicians involved in imaging coronary arteries to understand the importance of coronary calcification as a marker of atherosclerosis. Significance of Coronary Calcification Risk factors for coronary disease cannot be equated with actual disease, whereas coronary calcification is a marker of coronary atherosclerosis, regardless of the number of risk factors Stanford W. RadioGraphics. 1999; 19: Opening Plenary Session: RSNA 1998 Guerci et al. JACC 1998 Significance of Coronary Calcification. The detection of any coronary calcium outperforms Framingham risk score as a first step in screening for coronary atherosclerosis Ordinal scoring of coronary artery calcifications on low-dose CT scans of the chest is predictive of death from cardiovascular disease Johnson KM, Dowe DA. AJR 2010; 194: Shemesh J, et al. Radiology 2010; 257: What we can and cannot see coming We are trained to report on all the findings that we see May be able to offer even more clinically relevant information that is based not on what we can see at least at first glance What should we report? How much unrequested information should we include? Will this have a positive impact on patient care? What are the costs and are those costs worth it? (Is coronary calcium the new pulmonary nodule?) Lee CI and Forman HP. Radiology 2010; 257:

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