May 9, 2016 1Presented by: Michael J. Blaha

Michael J. Blaha MD MPH

Coronary Artery Calcium Scoring in Young and Low Risk Patients

Impact on Lipid-Lowering Pharmacotherapy Choices

Talk Outline

1. Rationale for clinical CVD risk prediction2. Weaknesses of existing CVD risk scores3. Coronary artery calcium (CAC), “disease

scores”, and “risk integration”4. CAC – not rare in young patients, prognostic!5. CAC and current prevention guidelines6. Clinical practice: CAC for guiding therapy

May 9, 2016 2

Rationale for Clinical CVD Risk Prediction

Part I

May 9, 2016 3

Level of Risk Factor

Prop

ortio

n of

Pop

ulat

ion

Optimal Borderline Elevated Very Elevated

Risk Factor Distribution

Level of Risk Factor

Rel

ativ

e R

isk

of C

VD

Elevated Very Elevated

Risk Factors and CVD Risk

High relative risk

Optimal Borderline

Level of Risk Factor

Tota

l CVD

Dea

ths

Elevated Very Elevated

Risk Factors and Total Number of Deaths

Total Number of Deaths

Optimal Borderline

Weaknesses of Present CVD Risk Scores

Part II

May 9, 2016 7

0 10 20 30 40 50 60 70 80 90

AGE 

RISK

 Traditional 10‐Year Risk Model

ATHEROSCLEROSIS

Risk Factor Exposure??

Outcomes??

9

Framingham Risk Score - MenAgeYears Pts20-34 -935-39 -440-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1275-79 13

CHD RiskPts 10-Yr

CHD Risk< 0 < 1%

0 1%1 1%2 1%3 1%4 1%5 2%6 2%7 3%8 4%9 5%

10 6%11 8%12 10%13 12%14 16%15 20%16 25%

> 17 > 30%

Systolic Blood Pressure

Untreated Treated<120 0 0120-129 0 1130-139 1 2140-159 1 2> 160 2 3

Total Cholesterol(mg/dL) 20-39 40-49 50-59 60-69 70-79<160 0 0 0 0 0160-199 4 3 2 1 0200-239 7 5 3 1 0240-279 9 6 4 2 1280 11 8 5 3 1

Cigarette SmokingNonsmoker 0 0 0 0 0Smoker 8 5 3 1 1

HDL-C(mg/dL) Pts> 60 -150-59 040-49 1< 40 2

HOW GOOD IS THE FRS AT PREDICTING MI? AKOSAH ET AL JACC 2003

222 patients with 1st acute MI, no prior CADmen <55 y/o (75%), women <65 (25%), no DM

75% did not qualify for pharmacotherapy

High Risk Intermediate Risk Low Risk

18%

12%

70%

New 2013 ASCVD Risk Calculator

Risk Factor Units Value

Acceptable range of values

Optimal values

Sex M or F M or FAge years 20-79Race AA or WH AA or WHTotal Cholesterol mg/dL 130-320 170HDL-Cholesterol mg/dL 20-100 50Systolic BP mm Hg 90-200 110Treatment for High BP Y or N Y or N NDiabetes Y or N Y or N NSmoker Y or N Y or N N

0.1

.2.3

.4.5

Pred

icte

d 10

-Yea

r Ris

k

40 50 60 70 80AGE

Framingham Risk Score ACC/AHA CVD Risk Score

Percent of U.S. Adults Who Would Be Eligible for Statin Therapy for Primary Prevention, According to Set of Guidelines and Age Group.

Pencina MJ et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1315665

Coronary Artery Calcium and Risk Integration

Part III

May 9, 2016 14

Continuum of Atherosclerosis Propagation Prior to a CHD Event

Genetics

Environment

Biomarkers

Risk Factors

Subclinical Atherosclerosis

Overt CAD

“Funnel”

0 10 20 30 40 50 60 70 80 90

AGE 

RISK

 Subclinical Disease Detection Model

Integrates Risk Exposure!!

Risk Factor vs. Disease Score

RISK FACTOR

• Measures increased risk for developing disease

• Separates risk elements• Usually mild risk

predictive value• Cancer analogy – high

hormone levels in breast cancer

DISEASE SCORE

• Measures the disease itself

• Integrates risk exposure• Usually a powerful

predictor of risk• Cancer analogy –

detection of suspicious nodule on mammography

~1 mSv

Relationship of Calcification to Coronary Atherosclerosis

May 9, 2016 19

20%

Rumberger, Circulation 1995

CAC Is Not Rare in Young Patients and is

Highly Prognostic! Part IV

May 9, 2016 20

CARDIA: CAC in Asymptomatic Individuals Age 33-45

21Rozanksi and Berman, JACCi 2013

CAC = 0 vs. Minimal CAC (1‐10)

• CAC=0 predicts excellent survival with 10‐year event rates of ~1%

• CAC 1‐10 patients had a 2‐3x increased risk for mortality vs. CAC=0

Blaha et al., JACC Cardiovasc Imaging, 2009.; Budoff et al., Am Heart J, 2009.

Tota-Maharaj, Blaha, et al. European Heart Journal. 2014.

0

10

20

30

40

<45 45-54 55-64 65-74 ≥75

0.7 0.6 1 2 2.8

1.6 1.2 3.7 5.913.8

6.83.2 5.5 9.6

20

27.6

7.5 11.719.9

37.9

Mortality/1000 person years

Age

CAC=0 CAC 1‐100 CAC 101‐400 CAC>400

Tota-Maharaj, Blaha, et al. European Heart Journal. 2014.

25

26

27

28

29

30

31

32

CAC and Prevention Guidelines

Part V

May 9, 2016 33

New ACC/AHA Guidelines –Primary Prevention

The Risk Discussion

Recommendations for Use of Newer Risk Markers After Quantitative Risk Assessment

If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following—family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making.†

I IIaIIb III

†Based on new evidence reviewed during ACC/AHA update of evidence.

37

38

Clinical Application –CAC for Guiding Lipid

PharmacotherapyPart VI

May 9, 2016 39

40

Continuum of ASCVD Risk

Primary Prevention

Advanced Subclinical 

Atherosclerosis?

Secondary Prevention

Blaha MJ, AJC 2016

The Young “Lower Risk” Patient: Spectrum of Coronary Atherosclerosis

CAC = 0 CAC >0  Advanced CAC

Focus on lifestyle therapy and discuss statin 

therapy

Recommend statin therapy 

Recommend statin therapy and discuss 

aggressive LDL‐C lowering to <70 mg/dL with statin 

+ ezetimibe/PCSK9 inhibitor?

Blaha MJ, AJC 2016

SUMMARY AND TAKE HOME: CAC for Young Patients When Individualization of

Prevention Is Required!!

1. When Risk/Decision to Treat is Uncertain– Family History– Metabolic syndrome– Non-White, non-AA– Rheumatologic Diseases, etc– Borderline Lipids

2. Statin Reluctant Patient3. Statin Intolerant Patient4. Decisions for Non-Statin Add-on Therapy

May 9, 2016 43

MESA CHD Risk Score

May 9, 2016 44

The MESA CHD Risk Score

THANK YOU!!!!

May 9, 2016 46

Back-Up Slides

Part VII

May 9, 2016 47

HU x-factor(peak w/in lesion)

130-199 1

200-299 2

300-399 3

>400 4

Area = 15 mm2, Peak CT = 450Score = 15 x 4 = 60

Area = 8 mm2, Peak CT = 290Score = 8 x 2 = 16

Agatston Score = CAC area x maximal density factorCalculation of Agatston Score

Agatston AS et al. JACC 1990;15:827-32Images: Rumberger JA Mayo Clin Proc 1999;74:243-52

May 9, 2016 49

Warranty Period of CAC=0 in Years

15% (NNS~6) 20% (NNS=5) 25% (NNS=4)

Males Females Males Females Males Females

All 3.1 3.6 3.5 4.9 4.6 6.4

Low Risk 5.4 5.8 6.4 6.9 7.3 7.9

Intermediate Risk 3.2 3.3 4.3 4.3 4.8 6.0

High Risk 2.9 2.9 3.1 3.2 3.2 3.5

Warranty Period of CAC=0

MESA Study CAC Tools

May 9, 2016 50

MESA CAC Reference Values

May 9, 2016 51

52

53

54

0

1 to 99≥100

0

5

10

15

20

25

30

<1.801.80 to 2.57

2.58 to 3.34≥3.35

4.73.5

2.63.0

14.0

6.710.5

10.2

26.1 26.1 28.925.6

CA

CRat

e of

CVD

per

1,0

00 p

erso

n-ye

ars

CAC and LDL Cholesterol

Martin SS, et al. Circulation. 2013.

CAC vs CTA slide?

May 9, 2016 56