Coronary Artery Calcification Dharmendra A. Patel, MD MPH Director, Echocardiography Laboratory Associate Program Director Cardiovascular Disease Fellowship Program Erlanger Heart and Lung Institute UT College of Medicine, Chattanooga, TN None Financial Disclosures Objectives Review coronary artery calcium scan and scoring methodology Review data regarding coronary artery calcification and CV risk stratification Discuss current guideline recommendations Heart Disease Statistics At-a-Glace 2017 Heart Disease (including Coronary Heart Disease, Hypertension, and Stroke) remains to be the No. 1 cause of death in the US. Coronary heart disease accounts for 1 in 7 deaths in the US, killing over 360,000 people a year. About 790,000 people in the US have heart attacks each year. Of those, about 114,000 will die. Average age at the first heart attack is 65.3 years for males and 71.8 years for females. Approximately every 40 seconds, an American will have a heart attack. The estimated direct and indirect cost of heart disease in 2012 to 2013 (average annual) was $199.6 billion. Heart attacks ($11.5 billion) and Coronary Heart Disease ($10.4 billion) were 2 of the 10 most expensive hospital principal discharge diagnoses. Between 2013 and 2030, medical costs of Coronary Heart Disease are projected to increase by about 100 percent. https://healthmetrics.heart.org/wp-content/uploads/2017/06/heart-disease-and-stroke-statistics-2017-ucm_491265.pdf At least 25% of patients experiencing non-fatal acute MI or sudden death had no previous symptoms Identification of asymptomatic individuals at greater risk of future CV events is fundamental for the implementation of preventive strategies. Risk Scores are very useful and should be used as the initial method of stratification, although they are able to predict only 65-80% of future CV events Coronary Artery Calcium Radiographic detection of coronary artery calcification (CAC) in vivo by fluroscopy described in 1950s -Blankenhorn DH, Stern D. Calcification of the coronary arteries. Am J Roentgenol Radium Ther Nucl Med. 1959 1
Evolving CT Technology Electron Beam CT scan (EBCT) in early 1980s permitted noninvasive and quantitative detection of CAC now obsolete Multi Detector CT (MDCT) with higher temporal resolution - current Coronary Artery Calcium Scan No special preparation, nor medication restrictions. Non-contrast scan Patient lies in CT scanner for about 10 minutes and must hold breath between 10-30 seconds during imaging. Radiation exposure: 0.7-3.0 msv Avg. yearly natural background exposure in US: 3 msv Diagnostic cardiac catheterization: 4.5 msv Coronary Artery Calcification Score Agatston Score Based on area and density of calcified plaques Typical report includes: Agatston score for each major coronary artery Total Agatston score for the patient Several representative images CAC Scoring CAC Score Coronary Plaque 0 Absence 1-99 Mild 100-399 Moderate >400 Severe Examples of Coronary Artery Scans CAC and CV Risk Stratification 2
Cumulative Survival 6/6/2018 CAC and Traditional Risk factors in Asymptomatic Individuals CAC Score and Framingham Risk Score, along and in combination, as Predictor of major CV events Nasir K et al. Circ Cardiovasc Imaging. 2012;5:467-473 Neves PO et al. Radiol Bras. 2017;50:182-189 All Cause Mortality and CAC Scores Long Term Prognosis in 25,253 patients 1.00 0.95 0.90 0.85 0.80 0 (n=11,044) 1-10 (n=3,567) 11-100 (n=5,032) 101-299 (n=2,616) 300-399 (n=561) 400-699 (n=955) 700-999 (n=514) 10.4 Fold Increased Risk CAC and Risk of Major CV Events in Asymptomatic Patients Pooled data from 6 large studies: 27, 622 Patients CAC score of 100-400 -relative risk of 4.3 (95% CI:3.1-6.1); CAC score of 401-999 -relative risk of 7.2 (95% CI:5.2-9.9); CAC score = 1000 -relative risk of 10.8 (95% CI:4.2-27.7). 0.75 0.70 2 =1363, p<0.0001 for variable overall and for each category subset. 1,000+ (n=964) 0.0 2.0 4.0 6.0 8.0 10.0 12.0 Time to Follow-up (Years) Budoff, et al. JACC 2007; 49: 1860-70 ACCF/AHA 2007 Consensus Document on CAC MESA (Multi ethnic Study of Atherosclerosis 6722 individuals Multi-ethnic population 162 coronary events 89 Major events MESA (Multi ethnic Study of Atherosclerosis MESA (Multi ethnic Study of Atherosclerosis Detrano R, et al. NEJM 2008;358:1336-1345 Detrano R, et al. NEJM 2008;358:1336-1345 3
Prognostic Power of CAC in Asymptomatic Patients 5 Year Mortality Rates in Framingham Risk Subsets by Coronary Calcium Score *p<0.001 * * * Hecht HS, Narula J. J Diabetes 2012;4:341-50 Shaw et al. Radiology 2003; 228:826-833 CAC vs Other Markers 0 CAC Score and Event rate Raggi et al. demonstrated annual event rate of 0.11% in asymptomatic patients with a CAC score of 0 (10-year risk of 1.1%) St.Francis Heart Study: CAC of 0 associated with 0.12% annual event rate over 4.2 years MESA: CAC of 0 associated with 0.11% annual event rate Adjusted HRs for comparisons of highest vs lowest quartiles after adjusting for traditional risk factors The Rotterdam Study. Ann Intern Med. 2012;156:438-444 0 CAC Score and Event Rate Irrespective of number of risk factors, absence of calcified plaque conveys very low 10-year risk (1.1%-1.7%) > 400 CAC Score Only in CAC>400 the pre-test probability is sufficiently high to warrant stress testing in select individuals (IIb) Nasir K et al. Circ Cardiovasc Imaging. 2012;5:467-473 4
Reclassification of Framingham Risk Score Risk by CAC Primary Prevention Outcome Studies Effect of CAC on Primary Prevention Patient Adherence Risk Factor Changes After CAC Scan EISNER Randomized Controlled Trial Parameters No SCAN CACS P Change in LDL-C -11 mg/dl -29 mg/dl <0.001 Change in SBP -5 mm Hg -9 mm Hg <0.001 Exercise 36% 47% 0.03 New Lipid Rx 19% 65% <0.001 New BP Rx 18% 46% <0.001 New ASA Rx 7% 21% <0.001 Lipid Adherence 80% 88% 0.04 Rozanski. Berman. EISNER. JACC 2011;57:1622. Effect of Treatment in Asymptomatic Patients St. Francis Heart Study: 1005 asymptomatic individuals, 50-70 years with CAC score at or above 80 th percentile for age and gender Treatment (atorvastatin 20 mg + Vit C + Vit E) vs. Placebo. Mean duration: 4.3 years No effect of treatment on progression of CAC score with nonsignificant trend toward a lower rate of composite CV events (6.9 vs 9.9%, p=0.08) The effect of statins and other therapies on CAC progression and patient outcomes has conflicting data so far and there is as of yet no clear evidence of improvement in outcomes. Starting pharmacological therapy to prevent coronary heart disease based solely upon the presence of CAC is not recommended. 5
CAC Progression and Serial Scanning Progression of CAC and risk of first MI (41 events) in 495 asymptomatic patient receiving cholesterol lowering therapy CAC Progression and Serial Scanning Insufficient data at present No current guideline-supported serial scan recommendations nor outcome studies documenting its effectiveness Use of % increase in relation to initial exam results in overestimation of progression in low initial score Routine Quantification of CAC progression in NOT recommended at present. Raggi P et al. Artherioscler Thromb Vasc Biol 2004;24:1-7 CAC and Symptomatic Coronary Artery Stenosis CAC is a better marker of the extent of coronary atherosclerosis than the severity of stenosis. 0 CAC score is not reliable indicator of absence of significant stenosis in symptomatic patients Subgroup of the CONFIRM registry, which included 10,037 symptomatic patients and showed coronary stenosis 50% and 70% in 3.5% and 1.4%, respectively, of the patients with a CAC score of zero. CAC and Clinical Practice Guidelines 2010 ACC/AHA Guideline for Screening in Asymptomatic Adults I IIa IIb III I IIa IIb III 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). 2010 ACC/AHA Guideline for Screening in Asymptomatic Adults Asymptomatic low risk (<6% 10-year risk) patient should no undergo CAC for cardiovascular risk assessment (IIIb No benefit) I IIa IIb III In asymptomatic adults with diabetes, 40 years of age and older, measurement of CAC is reasonable for cardiovascular risk assessment. 6
2013 ACC/AHA Guideline for Screening in Asymptomatic Adults CAC appropriate to inform treatment decision making if after quantitative risk assessment, a risk based treatment decision is uncertain (IIb) After discussing with the patient, when the decision to initiate statin therapy is difficult to make in selected individuals who are not in one of the four groups benefiting from the use of statin, atherosclerotic cardiovascular disease (ASCVD); primary elevation of low-density lipoprotein cholesterol (LDL-C) 190 mg/dl; 40 75 years of age with diabetes and an LDL-C of 70 189 mg/dl; 40 75 years of age without ACD or diabetes, with an LDL- C of 70 189 mg/dl and a 7.5% estimated 10-year risk of ACD. Summary Starting with a quantitative risk-based assessment, the patient and clinician first calculate the 10-year risk. If, after discussion, they are uncertain whether the individual patient is likely to benefit from initiating a statin, obtaining CAC score would be reasonable. Finding a CAC score of 0 in someone otherwise thought to be in a net benefit group is a powerful reason to consider withholding statin therapy. Likewise, the presence of a high CAC score in an individual at only moderate predicted risk should be a powerful motivator to initiate and adhere to statin therapy. Summary CAC useful for CV risk assessment in selected asymptomatic adults at intermediate risk (10-20% 10 year risk) when result is reasonably expected to change management based upon reclassification of risk CAC measurement should be avoided in asymptomatic adults with low (<10% 10 year risk) or high (>20% 10 year risk) 7