Northwestern University Feinberg School of Medicine

Donald M. Lloyd-Jones, MD ScM FACC FAHASenior Associate Dean

Chair, Department of Preventive Medicine

Director, Northwestern University Clinical And Translational Sciences (NUCATS) Institute

Eileen M. Foell Professor of Preventive Medicine and of Medicine

Promise and Pitfalls of Lifetime Risk

Assessment for CVD

Northwestern University Feinberg School of Medicine

Donald M. Lloyd-Jones, MD ScM FACC FAHASenior Associate Dean

Chair, Department of Preventive Medicine

Director, Northwestern University Clinical And Translational Sciences (NUCATS) Institute

Eileen M. Foell Professor of Preventive Medicine and of Medicine

10-Year vs. Lifetime Risk Assessment

for Cardiovascular Disease

Disclosures

• No RWI

• Grant support: NHLBI

• Member of NHLBI ATP-IV, Risk Assessment

Working Group and Integrated Guidelines

Panels

Current Paradigm for Risk Estimation and

Treatment: ATP-III

Estimate 10-year risk (FRS)

<10% >20% or DM10-20%

Further testing

Lifestyle

and drug therapy

Lifestyle

modification

“Intensity of prevention efforts should match

the absolute risk of the patient”

ATP-III Estimated 10-Year Risk:

Cases• 60 yo man; TC 250; HDL 30; SBP 150 on Rx;

Smoker; +DM

HIGH RISK (>20%)

• 40 yo woman; TC 180; HDL 60; SBP 120; Non-smoker; No DM

LOW RISK (<1%)

• 45 yo man; TC 230; HDL 40; SBP 135; Non-smoker; No DM

• 45 yo man; TC 275; HDL 50; SBP 160; Non-smoker; No DM

??????

0

5

10

15

20

25

30

Total cholesterol (mg/dL)160200240160200240

2535

45

HDL-c

(mg/dL)Pre

dic

ted

10-Y

ea

r R

isk

(%

)

Smoker Non-smoker

SBP 130 mm Hg

0

5

10

15

20

25

30

Total cholesterol (mg/dL)160200240160200240

2535

45

HDL-c

(mg/dL)Pre

dic

ted

10-Y

ea

r R

isk

(%

)

Smoker Non-smoker

SBP 150 mm Hg

10-Year

Predicted

Risks in

ATP Risk

Assessment

Tool:

Man, Age 45

Cavanaugh-Hussey, Berry,

Lloyd-Jones, Prev Med 2008.

0

5

10

15

20

25

30

Total cholesterol (mg/dL)160200240160200240

3545

55

HDL-c

(mg/dL)Pre

dic

ted

10-Y

ea

r R

isk

(%

)

Smoker Non-smoker

SBP 150 mm Hg

0

5

10

15

20

25

30

Total cholesterol (mg/dL)160200240160200240

3545

55

HDL-c

(mg/dL)Pre

dic

ted

10-Y

ea

r R

isk

(%

)

Smoker Non-smoker

SBP 130 mm Hg10-Year

Predicted

Risks in

ATP Risk

Assessment

Tool:

Woman, Age 55

Cavanaugh-Hussey, Berry,

Lloyd-Jones, Prev Med 2008.

Pitfalls of Short-Term Risk Estimates

• Vast majority of younger adults (men <50 and women <70) are considered to be at “low risk” regardless of RF burden

Weight of age

10-year risk window

Clinical treatment thresholds imposed

• Low risk No risk

• Importance of addressing multiple moderate or single elevated risk factors for long-term CHD prevention

• Reliance solely on estimates of short-term absolute

risk to communicate risk and make treatment

decisions is problematic

Can’t we just take the 10-year risk estimate

and fudge it to give us along-term risk estimate?

10-Year vs. Lifetime Risk for CHD

by FHS Risk Score Tertile

Men Women

Tertile of 10-Year Predicted Risk

Tertile of 10-Year Predicted Risk

Index Age Low Mid High Low Mid High

40 10-yr risk 0.3% 2% 11% 0% 1% 3%

Lifetime* 36% 35% 42% 12% 17% 30%

50 10-yr risk 4% 11% 15% 1% 1% 8%

Lifetime† 38% 43% 45% 23% 28% 34%

* Lifetime risk through age 80 † Lifetime risk through age 94

Lloyd-Jones et al, AJC 2003

10-Year vs. 30-Year Risks for CVD

• Rank order generally maintained

• Estimating 30 year risk 10-year risk x3 does not work (underestimates risk)

Updating age does not work (overestimates high/underestimates low risk)

Unadjusted model does not work (overestimates risk)

Pencina et al, Circ 200911

Men Women

Rationale: Lifetime Risk Estimation

• Lifetime risk The absolute cumulative risk of an individual developing

a given disease before death

Accounts for risk of disease of interest, remaining life

expectancy, and competing causes of death

Reflects real-life risks and population burden of disease

better than Kaplan-Meier cumulative incidence

Allows for comparison of disease burden now and in

future

N Engl J Med 2012; 366; 321-329

The Cardiovascular Lifetime Risk

Pooling Project

• Methods – 18 datasets collected Limited access datasets from NHLBI

• ARIC, FHS, FOS, HHP, PRHHP

Datasets from NCHS

• NHEFS, NHANES II Mortality, NHANES III FU Studies

University of Michigan IUC

• EPESE, Hisp EPESE, Kaiser Old, Tecumseh

Internal study datasets

• CHS, MRFIT screenees, WHI-OS

NU DPM datasets

• CHA, PG, WE

• Up to 620,000 individuals; >12M p-y of follow up

All

Optimal

Not

OptimalElevated

SBP/

DBP

<120 and

<80

120-139 or

80-89

140-159 or

90-99

≥160 or

≥100 or

Rx

TC <180 180-199 200-239≥240 or

Rx

DM No No No Yes

Smoking No No No Yes

Aggregate Risk Factor Burden

Lloyd-Jones, Circulation 2006; 113: 791-798

1 Major

≥2 Major

Lifetime Risks for All ASCVD Cardiovascular Lifetime Risk Pooling Project

2 Major RFs

1 Major RF

1 Elevated RF

1 Not Optimal RF

Optimal RFs

Attained Age

Cum

ula

tive

Ris

k

Men, Age 45

Lifetime Risks* for ASCVD:Cardiovascular Lifetime Risk Pooling Project

RF BurdenIndex Age 45 y Index Age 55 y

Men Women Men Women

All Optimal1.4%

(0-3.4)

4.1%

(0-8.2)

14.6%

(1.0-28.3)

10.1%

(0-25.0)

≥1 Not Optimal31.2%

(17.6-44.7)

12.2%

(4.6-19.7)

19.7%

(11.9-27.4)

13.3%

(5.5-21.1)

≥1 Elevated35.0%

(26.8-43.2)

15.6%

(10.3-20.9)

33.9%

(27.9-39.8)

15.3%

(11.3-19.3)

1 Major39.6%

(35.7-43.6)

20.2%

(17.2-23.2)

32.2%

(29.1-35.2)

16.7%

(14.5-19.0)

≥2 Major49.5%

(45.0-53.9)

30.7%

(26.3-35.0)

46.8%

(43.0-50.7)

29.2%

(26.2-32.3)

* To age 80

Can longer-term risk estimatesprovide a useful adjunct to

10-year risk estimates?

Lifetime Risk for ASCVD by RF Strata

Framingham Heart Study, Age 50

Attained Age

Ad

j. C

um

ula

tive

Ris

k

5%

36%

50%

69%

8%

27%

50%

Men Women

46%

39%

Lloyd-Jones, Circulation 2006

2 Major RFs

1 Major RF

1 Elevated RF

1 Not Optimal RF

Optimal RFs

0

2

4

6

8

10

12

14

16

18

20

20-29 30-39 40-49 50-59 60-79

Distributions of 10-Year and

Lifetime Risk Strata by Age and Sex US Adults, NHANES 2003-2006

0

2

4

6

8

10

12

14

16

18

20

20-29 30-39 40-49 50-59 60-79

Marma, Circ CQO 2010

Age

Ind

ivid

uals

(m

illi

on

s)

High 10 y

Low 10 y/High Life

Low 10 y/Low Life

Men Women

56% (87,000,000) have low short-term but high lifetime predicted risk

Cases Revisited

• High risk is high risk: Treat aggressively

• Low risk is low risk for now: Congrats and keep it that way

• 45 yo men; TC 230 (275); HDL 40 (50); SBP 135 (160); Non-smoker; No DM 10-Year Risk for CHD: 5% (7%)

Lifetime Risk for CVD: 46% (70%), AND

~10 (>12) year shorter lifespan

• Which message should we give him?

• \

• LR for Total CVD (CHD, Stroke, HF, CVD death):

Men: 60%; Women: 56%

Varies by aggregate RF burden

Wilkins, JAMA 201222

Compression of Morbidity

Wilkins, JAMA 201223

1.8 y

3.5 y

14 y

Competing CI for CVD and Non-CVD

Events by RF Burden: Female, Age 45

0%

20%

40%

60%

80%

100%

A

ll O

pti

mal

≥1

No

t O

pti

mal

≥1

Ele

vate

d

1

Maj

or

- B

P

1

Maj

or

- T

C

1

Maj

or

- D

M

1

Maj

or

- S

mo

ker

2

Maj

or

- S

mo

ker,

DM

2

Maj

or

- S

mo

ker,

TC

2

Maj

or

- S

mo

ker,

BP

2

Maj

or

- D

M, B

P

2

Maj

or

- D

M, T

C

2

Maj

or

- B

P, T

C

3

Maj

or

- S

mo

ker,

DM

,

BP

3

Maj

or

- S

mo

ker,

DM

,

TC

3

Maj

or

- S

mo

ker,

BP

, TC

3

Maj

or

- D

M, B

P, T

C

A

ll 4

Maj

or

CVD Non-CVD Death Event-Free

A New Risk Estimator?

Risk for Endpoint

Risk Factor Units Value Endpoint 10-Year

To Age

90

Gender M or F M Hard CHD 1.4% 42%

Age years 45 F/NF Stroke 0.2% 21%

Total Chol mg/dL 230

Hard

ASCVD1.5% 46%

HDL- C mg/dL 40 Alive & CVD-Free 14%

Systolic Blood

Pressure mm Hg 135

Treatment for

Hypertension (if

SBP >120) Y or N NVascular Age 54

Current Smoker Y or N N

Estimated

Life-Years Lost>10

New Paradigm for Risk Estimation?

Estimate 10-year risk (FRS)

<10% 20% or DM10-20%

Estimate lifetime risk

Treat

Lifestyle modification

<40% 40%

Lloyd-Jones Curr Opin Lipidol 2006

Summary

• Lifetime risk estimates can provide an

important adjunct to 10-year risk estimates

Help with “high-risk strategy”

- Identify younger individuals with low short-term but

high lifetime risk

Help with “population strategy”

- Communicate risk

- Raise awareness of disease

- Motivate lifestyle change/adherence to therapy

• Obviously, data

Acknowledgments

• NHLBI R21 & LADs

• Sean Coady, NHLBI

NU FHS/NHLBI

Alan Dyer Mark Huffman Dan Levy

Jarett Berry John Wilkins Marty Larson

Dan Garside Chintan Desai Ralph D’Agostino

Shelly Cai Ranya Sweis Alexa Beiser

Hongyan Ning Joseph Kang Peter Wilson

Linda Van Horn Lihui Zhao Jim Cleeman

Phil Greenland U Minn Sudha Seshadri

Nori Allen Avis Thomas

28

Northwestern University Feinberg School of Medicine

Donald M. Lloyd-Jones, MD ScM FACC FAHASenior Associate Dean

Chair, Department of Preventive Medicine

Director, Northwestern University Clinical And Translational Sciences (NUCATS) Institute

Eileen M. Foell Professor of Preventive Medicine and of Medicine

10-Year vs. Lifetime Risk Assessment

for Cardiovascular Disease