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?

BEFORE THE DISCOVERY OF

LIPOPROTEINS …..

THE CASE FOR HDL

FRAMINHAM HEART STUDY

MR FIT

LIPID RESEARCH CLINICS

CORONARY DRUG PROJECT

FAMILIAL ATHEROSCLEROSIS TREATMENT

STUDY

HDL- ATHEROSCLEROSIS TREATMENT STUDY

ARBITER TRIALS

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.

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

STUDIES SUGGESTING NIACIN NOT

BENEFICIAL IN RISK REDUCTION BY

RAISING HDL

HDL

HDL-C= 50 HDL-C= 100

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

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

Study Overview

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

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

Effect of Pharmacologic Interventions on Cholesterol Efflux Capacity.

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

Conclusions

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

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