DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL...

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DOES HDL MATTER ANYMORE?

Transcript of DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL...

Page 1: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

DOES HDL MATTER ANYMORE?

Page 2: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

BEFORE THE DISCOVERY OF

LIPOPROTEINS …..

Page 3: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 4: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

THE CASE FOR HDL

Page 5: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

FRAMINHAM HEART STUDY

MR FIT

LIPID RESEARCH CLINICS

CORONARY DRUG PROJECT

FAMILIAL ATHEROSCLEROSIS TREATMENT

STUDY

HDL- ATHEROSCLEROSIS TREATMENT STUDY

ARBITER TRIALS

Page 6: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

CHD RISK:

HDL-C VS. LDL-C AS PREDICTOR*

0.0

1.0

2.0

3.0

100 160 220 8565

4525

LDL-C, mg/dL

HDL-C, mg/dL

Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A.

RR

of

CH

D A

fter

4 Y

* Data represent men aged 50–70 y from the Framingham Heart Study.

Page 7: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 8: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

HATS: CLINICAL EVENTS

24

3

21

14

22

9

0

5

10

15

20

25

30 E

ve

nt

Ra

te (

%)

No Antioxidants Antioxidants ± Antioxidants

Placebo ± vitamins

Niacin-simvastatin ± vitamins

Brown BG et al. N Engl J Med. 2001;345:1583

RRR=90%

RRR=36%RRR=60%

n = 38 n = 38 n = 42 n = 42 n = 80 n = 80

Brown BG et al. NEJM. 2001; 345: 1583-1592

Page 9: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

STUDIES SUGGESTING NIACIN NOT

BENEFICIAL IN RISK REDUCTION BY

RAISING HDL

Page 10: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 11: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 12: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 13: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 14: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

HDL

Page 15: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

HDL-C= 50 HDL-C= 100

Page 16: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 17: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

HDL METABOLISM AND

REVERSE CHOLESTEROL TRANSPORT

A-I

Liver

CE

CE

CEFCFC

LCATFC

Bile

SR-BI

A-I

ABC1 = ATP-binding cassette protein 1; A-I = apolipoprotein A-I; CE = cholesteryl ester; FC = free cholesterol; LCAT = lecithin:cholesterol acyltransferase; SR-BI = scavenger receptor class BI

ABC1

MacrophageMature

HDL

Nascent HDL

Page 18: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 19: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl
Page 20: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

Original Article

Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and

AtherosclerosisAmit V. Khera, M.D., Marina Cuchel, M.D., Ph.D., Margarita de la Llera-Moya, Ph.D.,

Amrith Rodrigues, M.S., Megan F. Burke, B.A., Kashif Jafri, B.A., Benjamin C. French, Ph.D., Julie A. Phillips, Ph.D., Megan L. Mucksavage, M.Sc., Robert L.

Wilensky, M.D., Emile R. Mohler, M.D., George H. Rothblat, Ph.D., and Daniel J. Rader, M.D.

N Engl J MedVolume 364(2):127-135

January 13, 2011

Page 21: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

Study Overview

Khera AV et al. N Engl J Med 2011;364:127-135

Page 22: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

Odds Ratios for Coronary Artery Disease According to Efflux Capacity and Selected Risk Factors.

Khera AV et al. N Engl J Med 2011;364:127-135

Page 23: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

Effect of Pharmacologic Interventions on Cholesterol Efflux Capacity.

Khera AV et al. N Engl J Med 2011;364:127-135

Page 24: DOES HDL MATTER ANYMORE? · 2019. 10. 8. · 1.0 2.0 3.0 100 160 220 85 65 45 25 LDL-C, mg/dL HDL-C, mg/dL Reprinted with permission from Castelli WP. Can J Cardiol. 1988;4(suppl

Conclusions

Khera AV et al. N Engl J Med 2011;364:127-135


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