DOES HDL MATTER ANYMORE? · HATS: CLINICAL EVENTS 24 3 21 14 22 9 0 5 10 15 20 25 30) No...
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DOES HDL MATTER ANYMORE?
Transcript of DOES HDL MATTER ANYMORE? · HATS: CLINICAL EVENTS 24 3 21 14 22 9 0 5 10 15 20 25 30) No...
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
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Ra
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%)
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
