Professional Documents
Culture Documents
Ion
14.5-10.5 10.5 -----------------------------7.65 ---
Mobility
CIM Large Medium Small
Size, nm 11.8-9.7 9.7-8.2 8.2-7.2
Updated from Rosenson RS, et al. Clin Chem. 2011; 57(3)392-410.
Cholesterol* Per Particle Much Greater
for Large vs. Small HDL Particles
*FC= Free
Cholesterol
*CE= Cholesteryl
Ester
2b 2a 3a 3b 3c
Particle Diameters (nm)
14 9.4 8.2 7.3
2-5 ApoA1 per particle, decreases with particle size
HDL-C Gives Greater Weight to Larger Subclasses
HDL-P Gives Equal Weight to All Subclasses
Cholesterol Content Misrepresents
Particle Concentrations
MESA n=5314 Incident Diabetes
No Yes
LDL-C, mg/dl 118.0 117.6
HDL-C, mg/dl 52.4 46.7
LDL-P, nmol/l 1236 1322
HDL-P, nmol/l 34000 33000
Large HDL-P, nmol/l 6300 5100
Medium HDL-P, nmol/l 13900 12200
Small HDL-P, nmol/l 14200 16100
Adapted from Mackey RH et al. Diabetes Care. 2015: online before print.
Smaller HDL = More Functional?
Functions Smaller HDL Larger HDL
Cholesterol Efflux ABCA1* ABCG1
Anti-oxidative x
Anti-inflammatory x
Cytoprotective x
Endothelial/ Vasodilatory S1P? x
Anti-thrombotic x x
Anti-infectious x x
Camont L. et al. Trends in Mol Med. 2011; 17(10): 594-603.
Camont L, et al. Arterioscler Thromb Vasc Biol. 2013;33:2715-2723.
*Du XM et al. Circ Res. 2015 online before print.
HDL Proteome Relates to Function
+: Women
X: men
HDL-C, mg/dl
Spearman correlation
= 0.69; p < 0.0001. Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Differences in HDL-C vs. HDL-P
HDL-C HDL-P
HDL-P 0.69 -
Mean HDL size 0.68 0.34
Large HDL-P 0.87 0.53
Medium HDL-P 0.45 0.58
Small HDL-P -0.28 0.07
Triglycerides -0.48 -0.09
LDL-C -0.08 -0.13
LDL-P -0.38 -0.25
Small LDL-P -0.69 -0.38
HOMA-IR -0.38 -0.16
*spearman correlations adjusted for age, sex, race-ethnicity. N=5598
p<0.0001 for all.
Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Mean cIMT* by HDL-C or HDL-P Quartiles
HDL-C HDL-P
1010 1010
990 990
C C
I I
M 970 M970
T T
950 950
m m
930 930
910 910
<40 41-48 49-59 >60 29 29.1-33.1 33.2-37.8 >37.9
Adjusted base covariates* Adjusted base covariates*
Adj base cov*+LDLP Adj base cov*+LDLP
Adj base cov* +HDLP Adj base cov* +HDL-C
Adj base cov* +LDLP+HDLP Adj base cov* +LDL-P+HDL-C
*Adjusted for age, sex, race-ethnicity,
hypertension & smoking. Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Mean Difference* in Carotid IMT (m)
per SD increase in HDL-C or HDL-P
20
c 10
I
M 0
T
-10
(
-20
m
)
-30
-40
Covariates: Base* LDL-P HDL-P LDL-P, LDL-P, Base* LDL-P HDL-C LDL-P, LDL-P,
HDL-P HDL-P, HDL-C HDL-C,
LDL-C, LDL-C,
HDL-C TG HDL-P TG
*Adjusted age, sex, race-ethnicity,
hypertension & smoking. Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
CHD Risk per SD HDL-C or HDL-P:
Effects of adjusting for lipoproteins
1.50
1.25
HR(95%CI)
1.00
0.75
0.50
Base* LDL-P HDL-P HDL-P, HDL-P, Base* LDL-P HDL-C HDL-C, HDL-C,
LDL-P LDL-P, LDL-P LDL-P,
LDL-C, LDL-C,
HDL-C TG HDL-P TG
*All models adjusted for age, sex, race-ethnicity,
hypertension & smoking.
Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Mean cIMT* by HDL-C & HDL-P Tertiles
1060
1002
1040
1020
1001
1000
cIMT
m
980 954
957 945 p trend = n.s. for all HDL-C tertiles
960
958
940 951
920 916
918
900
Low
HDL-P Med
HDL-P p trend <0.05
High p trend = n.s.
HDL-P: HDL-P
<30.6, 30.6-36,1, 36.2 umol/l p trend <0.05
HDL-C:
<42, 43-54, >54, 55 mg/dl
*Adjusted for age, sex, race-ethnicity,
hypertension & smoking. Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Mean cIMT* by HDLC/ HDLP tertiles,
LDL-P 1236 nmol/l (median)
1082
1100
Low
HDL-P Med
HDL-P
High
HDL-P p for HDL-P trends = n.s.
*Adjusted age, sex, race-
ethnicity, hypertension &
smoking. Median= 1236 nmol/l Mackey RH et al. J Am Coll Cardiol. 2012: 60(6) 50816.
Mean cIMT* by HDLC/HDLP tertiles,
LDL-P < 1236 nmol/l (median)
1100
984
1050
c
I 1000 960 p trend = n.s. for all
940
M 929
950
T 923
910 897
900 896
m 850 855
Low
HDL-P Med
p trend =0.02
HDL-P
High
HDL-P p trend =0.09
p trend =0.06