Raul D. Santos

University of São Paulo

Brazil

Subclinical Atherosclerosis

Raul D. Santos

University of São Paulo

Brazil

Coronary Subclinical Atherosclerosis

Disclosure

• Honoraria received for consulting, speaker or researcher activities : Ache, Astra Zeneca, Amgen, Esperion, Kowa, Merck, MSD, Novo-Nordisk, PTC, Pfizer, Sanofi/Regeneron.3

Statins: Benefits and Risks

Collins R et al. Lancet 2016; 388:2532-2561

Statins in Primary Prevention: Overall Impact in 5 Years

Trials RRR ARD NNT in 5 years

All Cause Mortality

15 0.86 [0.80-0.93] −0.40% 250

CV Mortality 10 0.69 [95% CI, 0.54-0.88] -0.43% 233

Stroke 13 0.71 [95% CI, 0.62-0.82] -0.38% 263

MI 12 0.64 [95% CI, 0.57-0.71 -0.81% 123

Revascularization 7 0.63 [95% CI, 0.56-0.72] -0.66% 152

Composite Endpoint

13 0.70 [95% CI, 0.63-0.78] -1.39% 72

Chou et al. JAMA. 2016;316:2008-2024 5

However, we treat risk and not necessarily cholesterol!

How to improve?

6

Clinical case

• Mr. RSB, Caucasian, 55 year old man

• Administrator

• Asymptomatic and says his GP tested his cholesterol and said it has been high for many years!

• Father had an MI at age 58 years, no smoking, no HBP

• Exercises 3 times a week, eats well

• PE:– BMI 24.5 kg/m2, BP: 128/80 mmhg

– Rest Ok

7

What is Mr. RSB calculated Risk ?

Lipids (mg/dL)TC=240 TG- 150HDL-C=45LDL-C=165

RRR =30%ARR= 2.2%Rosuva 10

Borderline Risk

8

But Dr. Raul I don’t want to take statins if possible !

• I saw some guy on the internet and he said:

– May drive me diabetic

– May give me muscle pain

– Might alter my cognition

– Might worsen my exercise performance

– But I’m open to discussion cause I know you’re a nice guy !

9

…sometimes a picture values > 1,000 words !

10

CHD Death Rates and Coronary Artery Calcification (CAC) in 3 Asymptomatic Cohorts: USA, Brazil, and Portugal

Santos RD et al Atherosclerosis 2006;187:378-84

P<0.0001 for CAC

CAC prevalence adjusted for age, sex, blood pressure, dyslpidemia, DM, smoking

11

(n=17,563)

12Budoff et al. Eur Heart J 2018; 39:2401–2408 CAC> 100 = >7.5% 10-year risk

CAC and Prognosis

Yeboah, et al JAMA 2012 22;308(8):788-95

CAC reclassified 65% of individuals

CAC vs. Risk Factors

The Power of Zero !

14

Diabetes Duration and CAC Prognosis in MESA

.

Malik et al. JAMA Cardiol, 2017 (12):1332-1340. Years

CAC zero = 3.7% events/10 years

15 year Mortality CAC vs. No CAC

Valenti et al. JACC Cardiovasc Imaging. 2015 Aug;8(8):900-9

n=9715Time to mortality >1% per year

17

Patient 1

Zero CAC

Low cIMT (<50th percentile)

No family history CHD

No carotid plaque

No metabolic syndrome

Homocysteine <10 umol/L

Normal ABI (1.0 - 1.3)

hsCRP <2

BNP <100 pg/mL

No microalbuminuria

10.80.60.40.20

Framingham-Adjusted Likelihood Ratio

Intermediate Risk White Man

55 years old

Total cholesterol 250 mg/dL

HDL 40 mg/dL

Normal blood pressure

Blaha MJ et al. Circulation. 2016;133:849-58

Coronary Artery Calcification and Cardiovascular Events in Statin Treated FH: New Paradigm?

1.00

0.90

0.80

0.70

0 2 4 6 8 10Years of follow up

CAC = 0 CAC 1 - 100 CAC > 100

Survival free from MACE

Cu

mu

lative

MA

CE

fre

e s

urv

iva

l

206 molecularly proven heterozygousFH individuals

age 45±14 years 79.6% with high dose statin64% also with ezetimibe On treatment LDL-C 150±56 mg/dL

P=0.0003

CAC present in 105 (51%)

Follow-up median of 3.7 (quartiles: 2.7 – 6.8) yearsASCVD events (7.2%) Annualized event rate (1,000 patients/year) CAC 0 = 0

CAC 1-100= 26.4 (95% CI 12.9 - 51.8) >100 = 44.1 (95% CI 26.0 - 104.1)

Miname et al & Santos JACC Cardiovasc Imaging 2019 ;12:1797-1804

19

1

Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥190 mg/dL:

The M ulti-Ethnic Study of Atherosclerosis

Pratik B. Sandesaraa, Anurag Mehta

a, Wesley T. O’Neal

a, Heval M. Kelli

a, Vasanth

Sathiyakumarc, Seth S. Martin

c, Michael J. Blaha

c, Roger S. Blumenthal

c, Laurence S.

Sperling,a,b

aDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, 100

Woodruff Circle, Atlanta, Georgia, USA bEmory Heart Disease Prevention Center, Executive Park, 1605 Chantilly Drive Northeast,

Atlanta, Georgia, USA cJohns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, 601 North

Caroline Street, Baltimore, Maryland, USA

Correspondence: Pratik B. Sandesara

Department of Medicine

Division of Cardiology

Emory University School of Medicine

1462 Clifton Rd NE, Suite # 513

Atlanta, GA 30322

Tel: 404-712-9186

Fax: 404-712-0183

psandes@emory.edu

Sandesara et al. Atheroclerosis 2020 ;292:224-229

n=246LDL-C=215±27 mg/dL

37% CAC= Zero

20Eur Heart J Cardiovasc Imaging. 2019 Nov 8. pii: jez280. doi: 10.1093/ehjci/jez280. [Epub ahead of print]

RSB, 55 , MaleCalculated 10 year risk

7.3%LDL-C= 165 mg/dL

Grundy et al. 21

Back to the Case

CAC Scan 3 possibilities :

CAC= Zero CAC >100 CAC= 1-99

22

Nasir K et al. JACC 2015; 66:1657–68

CAC, Statin Indication and Risk LDL-C 70-189 mg/dL :MESA

41% no CAC57% no CAC71% no CAC

24

Back to the case: 55 year old male, LDL= 165 mg/dL, estimated 10-year ASCVD Risk 7.3% or more

Estimated Risk

5-7.5%

Observed Risk1,000

patients/year

NNT10 years

CAC= 0 1.5 (0.6-3.6) 223

CAC> 0 7.4 (4.7-11.8) 46

CAC 1-100 7.8 (4.6-13.2) 43

CAC>100 6.3 (2.4-16.8) 53

Risk > 7.5% + other statin

recommendations

Observed Risk1,000

patients/year

NNT10 years

CAC= 0 5.2 (4.0-7.0) 64

CAC> 0 12 (10.2-14.1) 28

CAC 1-100 8.8(6.8-11.4) 38

CAC>100 15.4 (12.5-18.9) 22

Adapted from Nasir K et al. JACC 2015; 66:1657–68

ASCVD Risk in MESA , CAC and NNT With Statins

N=4,758 (age 59 ± 9 years; 47% males)247 (5.2%) ASCVD events

Median FUP 10.3 (9.7 to 10.8) years 25

What about CT angiography?

26

Stefan B. Puchner et al. JACC 2014;64:684-692

High Risk Plaques on CT Angiography

CAC vs. CT Angiography

Takamura, J Atherosc Throm, 2017Min, Atherosclerosis, 2014

Conclusions

• LDL= cause of atherosclerosis

• Multifactorial disease not only cholesterol !

• LDL-C lowering prevents events

• However, we treat risk, greater risk = more benefit

• Coronary subclinical atherosclerosis (CAC) helps identify higher/lower risk= better precision

• CAC can be used to help decide start or not therapy

29