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Calcium scoring Is it still Relevant in 2013?

Safaa Al Mohdar, MD Consultant Cardiologist Zayed Military Hospital Abu Dhabi, UAE

Death From CVD World Wide 25 M

~15 M

Reddy NEJM 2004 (350)

Total Coronary artery plaque 20%

Calcified

20%

Fibrotic

80%

Lipid Rich

Plaque Detectable

By IVUS, Pathology

80%

Screening for CVD • Risk for CVD: – At the age 40: 50% of Men and 30% women – At the age 70: 35%of men and 24% women

• Immense problem • Atherosclerosis begins in childhood and progress with risk factors and life styleLong latent asymptomatic period • prevention

Global Risk factors Framingham Risk Score “FRS” • Office-based assessment interrogating CVD Risk factors such as , Age, Gender, smoking, BP and Cholesterol measurement.

• Classify people into 3 risk groups to develop CV event in the next 10 years to: Low risk < 10%

“Life style changes”

Moderate risk 10-20%

“ Target for screening”

High Risk >20%

“ CVD-risk equivalent “

Role for CVD screening

Shaw LJ Med Clin Am 2012 103-112

FRS: Good But NOT Good Enough • 70% of patients presented with ACS had “low” FRS and with only 10% defined as high risk* • A challenge in accurately define individual risk based on a population risk • FRS underestimate CVD risk in men< 60 and in women • Does not include patients with family Hx of CVD and metabolic syndrome, race/ ethinicity *Akosah et al , JACC 2003 41;1475-9

Biomarkers for prediction of Future CV events • • • • • • • • •

C-Reactive Protein B-type natriuretic peptide, Aldosterone Renin fibrinogen, D-dimer plasminogen-activator inhibitor Homocysteine Urinary albumin-to-creatinine ratio.

3209 participants attending a routine examination cycle of the Framingham Heart Study 10 biomarkers Follow up 7.4 years

Biomarkers and Risk Assessment

For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors Wang et al NEJM 355;25:2631-9

Imaging See it for your self,,,,, • “The best test for prediction of the risk of atherosclerosis is the demonstration of atherosclerosis”

Dr.Ernest Schaeffer, Editor-in-Chief of Atherosclerosis

Scan Protocol • Coronary calcium quantification is typically performed in axial images with either EBT or MDCT • Non contrast , low radiation scan • Scoring system: Agatston ,Ca Volume (mm₃), Ca Mass(mg)

Prognostic calcium scoring • • • • •

0= no CAC 1-99= Mild 100-399= Moderate 400-999= High-risk >1000= very high-risk

(Agatston score)

Greenland et al, JACC 2010 (56)

Recommendations for Calcium Scoring Methods I IIa IIb III

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).

Asymptomatic adults with Diabetes,40 years of age or older, measurement of CAC is reasonable for cardiovascular Risk assessment

Tylor et al JCCT 2010

Computed Tomography for Coronary Calcium should be considered for Cardiovascular Risk assessment in patients moderate CV Risk Class IIa

NICE Guidelines2010

St.Francis Heart Study Prediction of cardiac events in Asymptomatic patients Detected by EBT 5000 patients-Follow up 4.3 years 3.5

2.5

Relative Risk

Annual Event Rate (%)

3

2 1.5 1 0.5

CAC > 100 Vs >100

0

0 JACC 2005

10.8 10.6 10.4 10.2 10 9.8 9.6 9.4 9.2 9 8.8

10X

Cor. any event MI/SCD Event

>0 >100 >200 Baseline EBT Calcium Score

>600

St Francis Trial Double Blind Placebo controlled Trial of Atorvastatin in prevention of CV events among patients with high CAC Score

• 1000 patients,No Prior CVD, 50-70 yrs, CAC>80% of Age Gender: Randomized to Atorvastatin 20mg(N:490) OR Placebo (N:515) • Mean duration 4.3 yrs • LDL reduced by 39.1%, event rate reduced by 30% (6.9%Vs 9.9%) • Event rate were more significantly reduced in over all events in individuals with baseline CAC>400 (8.7% Vs 15%) 42% Reduction • NNT 16- Cost effective Arad et al JACC 2005(46) 166-172

long term prognosis in 25,253 patients.

All cause mortality and CAC Score

10.4

Budoff et al JACC 2007, (49) 1860-1870

â&#x20AC;˘ 6722 Men& Women. 39% White,29% Black,22%Hispanic and 12% Chinese â&#x20AC;˘ Follow up Median 3.8Yrs. 162 Coronary events including 69 non-fatal MI or Death from CAD Detrano et al NEJM 2008

MESA Study- 6722 patients: 3.8 years follow up Nonfatal MI & CV death 16

14.13

14

Hazard Ratio

12

10.26

10

8 6

4.47

4

2

Ref

0 None Detrano et al NEJM 2008

1-100

100-300

>300

PACC Study • 2000 healthy army personnel, Mean age 43 • CAC was associated with 11.8 fold increase risk for incidental Coronary heart disease(P0.002) in a cox model controlling for Framingham Risk Score.

• In young asymptomatic men, the presence of CAC provides substantial cost-effective, independent prognostic value in predicting incident CHD that is incremental; to measured coronary risk factors.

Tylor et al JACC 2005

Improve Adherence to Treatment

Taylor et al, JACC 2008 (14) 1337-41

2028 asymp 69+/- 6.2 yrs 9.2 follow up

JACC , 2010:1407–14

Rotterdam study

Kavousi et al,Ann Intern Med. 2012;156:438-444.

EISNER Study Early Identification of Subclinical Atherosclerosis

by Non invasive Imaging Research, • A prospective randomized Trial of 2,137 patients to compare the clinical impact of conventional risk factors modifications to that associated with the addition of CAC • Compared with the no-scan group, the scan group showed a net favorable change in: – – – –

Systolic BP (p=0.02) LDL cholesterol (p=0.04) Waist Circumference (p=0.01) Improvement in FRS(0.7+/-5.1 Vs 0.002+/-4.9,p=0.003)

Rozanski JAAC 2011

Eisner Study â&#x20AC;&#x201C; Costs Compared to no scan Group 0% -5%

Medication Costs

Procedure Costs

-10% -15% -20% -25% -30% -35%

-26%

Medication Costs Procedure Costs

-37%

-40% P < 0.005 for both measures Rozanski JAAC 2011

14,795 asymptomatic patients To evaluate the value of Number and Site of coronary calcified lesions Compared with the total score

William et al JACC imag,2008(1) 61-9

Level of Calcification Patients with Single lesion

J Am Coll Cardiol Img. 2008;1(1):61-69

Number of calcified lesions CAC>100

J Am Coll Cardiol Img. 2008;1(1):61-69.

What to do next? â&#x20AC;˘ When do you consider further cardiac investigations?

Inducible Ischemia

Shaw LJ Med Clin Am 2012 103-112

Classification of CAC Scores and Clinical conditions/ Recommendations commonly Incorporated Intro Clinical Reporting CAC Score

Calcified Plaque Burden

Likelihood of CAD

CHD Rick

0

No identifiable atherosclerotic plaque

Very Low

Very Low

1.10

Minimal Plaque burden

Very Low

Low

Optional

0

11.100

Mild Plaque burden

Low

Moderate

Consider2â&#x20AC;&#x2122; Prevention

0

101.400

Moderate Plaque burden

Low intermediate

401.1000

Extensive Plaque burden

Highintermediate

>1,000

Very Extensive Plaque burden

High

Berman,Ds et al.Sem Nuc Med 2007

Moderate High

Recommend ed Clinical Action 1 Prevention

2nd

Additional Testing

0

Consider if >75th percentile Prevention or diabetes or RF

High

2nd prevention

Yes

very High

2nd prevention

Yes

Symptoms and CCA 76 symptomatic patients and 1119 without

No symptoms symptoms

Berman et al JAAC (44) 2004

Rozanski et al Journ Nucl car sept,2007

Role of symptoms and CAC • Asymptomatic and have CACS< 100 is associated with low likelihood of Ischaemia BUT • Typical or atypical angina with LOWER CACS does NOT exclude ischaemia Rozanski et al Journ Nucl car sept,2007

Calcium Score “power of ZERO”

10

7.7 (P<0.001)

0.11% Annual rate CAC 0

Detrano et al NEJM 2008

Absence of Coronary Artery Calcification and All-Cause Mortality 1% /10 Years

J Am Coll Cardiol Img. 2009;2(6):692-700.

Copyright Š The American College of Cardiology.

All rights reserved.

The CONFIRM Registry Coronary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter Registry

27,125 patients, 10,037 symptomatic Patients Without known CAD. Mean age 57+/- 12 yrs. 56% Male.

51% 0 score Younger, Female lower burden CV Risk Factors 84% had No CAD 13% Non Obst 3.9% Obst lesions ( 1.4% >70%stenosis)

Villines et al JACC 2011 (58) 2533-40

<50% stenosis >50% stenosis Male Smokers Premature FHx

3.9% with CAC 0 and >50% stenosis Experienced and event Compared with 0.8% with CAC 0 and No obstructive CAD Conclusion: In symptomatic patients with CAC score 0,Obstructive CAD is possible and is associated With increased CV events

Villines et al JACC 2011 (58) 2533-40

AHA Circulation 2005 This recommendation to measure atherosclerosis burden, in clinically selected intermediate â&#x20AC;&#x201C;CAD risk patients (e.g, those with a 10%-20% Framingham 10-years risk estimate) to refine clinical risk prediction and to select patients for altered targets for lipid-lowering therapies

Calcium Scoring, Is It Still Relevant in 2013?

YES, In Carefully selected patients and special Clinical Settings

Summary • CAC is an excellent screening tool for atherosclerosis- It adds incremental informational beyond traditional Risk Factor Models • It should be to those used in patients with Intermediate FRS for CVD(1-3 Risk Factors) • It should be used in patients with family history premature CAD

Summary • Guide therapeutic decisions for both primary and secondary prevention • Absence of CAC in asymptomatic patients confers a very low risk for future CVD events “power of Zero” • Guide additional testing in selected patients

Huang Dee: Nai-Ching ( 2600 BC, First Medical Text)

Superior Doctors Medicore Doctors Inferior Doctors

Prevent the disease Treat the disease before evident Treat the full-blown disease

THANK YOU

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