Coronary artery calcium scoring. Con Aroney AM MD, FRACP, FCSANZ Queensland Cardiology

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1 Coronary artery calcium scoring Con Aroney AM MD, FRACP, FCSANZ Queensland Cardiology

2 Predicting cardiac events in asymptomatic people Risk Factors Hypertension Smoking Dyslipidemia Family History Diabetes/ Metabolic Syndrome Se homocysteine Se HS crp (inflammation) Ischemia Testing Stress Testing/ Stress Echo/ Stress Perfusion Study Identifying atherosclerotic disease PVD - Ankle Brachial Index Carotid disease doppler/ plaque area Coronary disease: CT calcium score (total atherosclerotic burden) CT angiography (luminal obstruction)

3 Risk factors How good are they in predicting events? In 87,000 men with heart attacks, 62% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). In 34,589 women with heart attacks, 53% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). 63% of the adult US population have 0 or 1 major risk factors (Circulation 2007) Almost all individuals with 0 or 1 risk factor are Framingham low risk" and therefore will not qualify for cholesterol lowering therapies. (JAMA 2001; 285: )

4 Risk factors How good are they in predicting events? In 87,000 men with heart attacks, 62% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). In 34,589 women with heart attacks, 53% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). 63% of the adult US population have 0 or 1 major risk factors (Circulation 2007) Almost all individuals with 0 or 1 risk factor are Framingham low risk" and therefore will not qualify for cholesterol lowering therapies. (JAMA 2001; 285: )

5 Risk factors How good are they in predicting events? In 87,000 men with heart attacks, 62% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). In 34,589 women with heart attacks, 53% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). 63% of the adult US population have 0 or 1 major risk factors (Circulation 2007) Almost all individuals with 0 or 1 risk factor are Framingham low risk" and therefore will not qualify for cholesterol lowering therapies. (JAMA 2001; 285: )

6 Risk factors How good are they in predicting events? In 87,000 men with heart attacks, 62% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). In 34,589 women with heart attacks, 53% had 0 or 1 major risk factors (Khot, et al. JAMA. 2003). 63% of the adult US population have 0 or 1 major risk factors (Circulation 2007) Almost all individuals with 0 or 1 risk factor are Framingham low risk" and therefore will not qualify for cholesterol lowering therapies. (JAMA 2001; 285: )

7 72% of myocardial infarctions occur in persons with LDL cholesterol <3.3mmol/l 13% of patients with fatal MI have no major risk factors. JAMA 2003: 290:891

8 Global Risk Scores Misclassify 75% of people Asokah et al. JACC 2003 Misclassify 90% of women Ridker et al. JAMA 2007

9 Risk factors are:

10 Risk factors are: poor at predicting outcomes

11 Risk factors are: poor at predicting outcomes poor at motivating patients to participate in preventative strategies to improve outcomes

12 "The best predictor of a life-threatening illness - is the early manifestation of a life-threatening illness." Sir Geoffrey Rose

13 Identifying atherosclerotic disease CT Coronary Calcium Score Identifies total coronary atherosclerotic burden additionally locates burden score for each coronary artery strong association with cardiac events and total mortality CT Coronary Angiogram Measures luminal obstruction inferior to selective angiography poorer spatial and temporal resolution lumen hidden by calcium Not a screening test IV contrast

14 Conflicts of interest I have no involvement whatever with CT coronary calcium scoring.

15 Coronary Disease Progression Calcified Plaque Detected by CT

16 The amount of calcified plaque (calcium score) correlates with the total atherosclerotic coronary plaque burden as determined by: Histological studies Rumberger Circulation 1995 Mautner Radiology 1994 Ultrasonic studies Mintz JACC 1997 Baumgart JACC 1997

17 Long-Term Prognosis Associated with Coronary Calcification: Study Design A cohort of 25,253 consecutive, asymptomatic individuals referred by their primary physician for CAC scanning to assess cardiovascular risk CAC scanning CAC Score 0 44% CAC Score % CAC Score % CAC Score % CAC Score % CAC Score >1000 4% 6.8 ± 3 yrs. follow-up Assessment of all-cause mortality Budoff, et al. JACC 2007; 49:

18 Long-Term Prognosis Associated with Coronary Calcification: Outcomes Cumulative Survival by Coronary Calcium Score Cumulative Survival (n=11,044) 1-10 (n=3,567) (n=5,032) (n=2,616) (n=561) (n=955) (n=514) ,000+ (n=964) c 2 =1363, p< for variable overall and for each category subset. Time to Follow-up (Years) Budoff, et al. JACC 2007; 49:

19 CCS and age and gender related mortality at 5 years Raggi et al. JACC 2008; 52:17-23

20 Cox proportional hazard cumulative survival for smokers and non-smokers by their coronary artery calcium score Shaw, L. J. et al. Eur Heart J :

21 Cox proportional hazards survival (n = 10,377) by CT coronary calcium measurements in subjects with and without diabetes mellitus (chisquare = 204, p < ) Raggi, P. et al. J Am Coll Cardiol 2004;43:

22 Cox proportional hazards cumulative survival for subjects with and without diabetes mellitus with a calcium score of 0 Raggi, P. et al. J Am Coll Cardiol 2004;43:

23 The Power of Zero A CAC score of 0 confers a 15-year warranty period against mortality in individuals at low to intermediate risk, unaffected by age or sex. Valenti V, B OH, Heo R, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9,715 individuals. JACC Cardiovasc Imaging. 2015;8:

24 Probability of survival free of events in 98 consecutive asymptomatic subjects with a calcium score 1,000 30% one year death/mi 50-60% two year death/mi Events = 12 deaths; 23 MIs Wayhs et al. JACC 2002; 39:225-30

25 Problems with ischemia testing asymptomatic persons Plaque burden not obstructive lesions predicts outcome best Can miss high risk persons Plagued by false positive results Costly Myocardial perfusion imaging has a high radiation load

26 Shaw et al. Radiology 2003; 228: Five-Year Mortality Rates in Framingham Risk Subsets by Coronary Calcium Score *p<0.001 * * *

27 CAC scoring provides more robust risk prediction than carotid intima media thickness, CRP, ankle-brachial index, absolute risk scores and family history of premature heart disease. Yeboah et al. JAMA. 2012;308: Yeboah et al. JACC 2016; 67:

28 When should I prescribe a statin? Almost half of the patients in the MESA JUPITER population had CAC scores of 0, and in this group, rates of coronary heart disease (CHD) events were 0.8 per 1000 person-years (< 0.1%). (Blaha et al. Lancet. 2011;378: ) Nearly three quarters of all coronary events were in the 25% of participants with CAC scores higher than 100 (20.2 per 1000 personyears or 2% per year). To prevent one CHD event, the predicted 5-year NNT with a statin was 549 for a CAC score of 0 94 for scores of for scores above 100 CAC demonstrated that 50% of the population who meet criteria for statins but have no measurable atherosclerosis would likely not benefit. Studies have shown that using CAC testing is more cost-effective than the current widespread statin use that is advocated by the ACC/AHA pooled cohorts.

29 On the basis of current guidelines from both NCEP and ACC/AHA: CAC scores < 75th percentile and < 300 are to be treated with low- to moderate-dose statins. CAC scores > 75th percentile or 300 are to be treated with high-dose statins. CAC score of zero should be considered for lifestyle modification, unless a compelling indication for statin already exists.

30 Coronary calcium scores may continue to increase despite intense statin therapy (Henein et al. Int J Cardiol 2011, Yazbek et al. PLoS One 2016) but with statins, plaque composition/morphology is associated with plaque regression and stable fibrocalcific plaques which are less vulnerable to development of ACS, including decreased in the lipid content of plaques reduced necrotic core, increased cap thickness reduced inflammatory burden improved endothelial function (Rodriguez-Granillo et al. Cardiovasc Diagn Ther 2016, Park et al JACC 2016)

31 When should I prescribe low dose aspirin? Individuals with CAC scores 100 had an estimated net benefit from aspirin regardless of their traditional risk status (NNT = 92; estimated 5-year number needed to harm [NNH] = 442 for a major bleed). Conversely, individuals with a score of zero were unlikely to benefit (5-year NNT = 2036 for individuals with a Framingham risk score [FRS] < 10% and 808 for FRS 10%; 5-year NNH = 442 for a major bleed). This was true for men and women and regardless of age. Miedema MD, Duprez DA, Misialek JR, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes. 2014;7:

32 Management depending on CAC Score Score of 0 reassurance, further coronary testing not required for at least 5 yrs lifestyle modification and BP control only lipid lowering therapy for severe dyslipidemia or multiple risk factors Score education, aggressive risk factor control, consider aspirin consider ischemia testing in high risk individuals repeat CAC scoring 2-3 year intervals aim for annualised increase <15% Score education, very aggressive risk factor control, aspirin regular ischemia testing 2-3 year intervals Score >1000 education, very aggressive risk factor control, aspirin yearly ischemia testing

33 Gnossos einai Dynami Knowledge is Power

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