Transcript Lipidaholics Graphics

National Health And Nutrition
Examination Survey III (NHANES):
Metabolic Syndrome in Normal Weight Americans
Metabolically Obese Normal Weight (MONW)
25
Blacks
Prevalence %
20
15
MEN
Hispanics
Whites
10
5
0
18.5-20.9
23.0-24.9
21.0-22.9
Body mass Index (kg/m2
25.0-26.9
Marie-Pierre St-Onge et al Diabetes Care 27:2222–2228, 2004
National Health And Nutrition
Examination Survey III (NHANES):
Metabolic Syndrome in Normal Weight Americans
20
Metabolically Obese Normal Weight (MONW)
Odds Ratio
15
10
Men
Women
OR of MS using NCEP Criteria but
excluding waist circumference
adjusted for age, ethnicity,
education, income and physical
activity, smoking, alcohol use,
PUFA, carbohydrate
& fiber intake
5
0
18.5-20.9
Referent Group
21.0-22.9
23.0-24.9
25.0-26.9
Body mass Index (kg/m2
For both sexes the development of the metabolic syndrome increased
significantly (P<0.001) with an increasing BMI category with and without the
waist circumference in the definition of the MS
Marie-Pierre St-Onge et al Diabetes Care 27:2222–2228, 2004
Relationship of Small LDL to
Triglyceride/HDL-C Ratio
Males
Cumulative Frequency (%)
100
80
60
Large LDL
Small LDL
40
20
In men, 76% of
the LDL
phenotype A
was less than
and 77% of
phenotype B
was greater
than the cutoff
of 3.8.
0
0
12
10
8
6
4
2
Triglyceride/HDL-C mg/dL Ratio
NMR Spectroscopy
Hanak, V. et al. Am J Cardiol 2004;94:219–222
Identifying IR Patients at Increased CVD Risk
1.0
1.0
A
0.9
0.8
0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
Sensitivity
0.9
B
0.3
0.3
TG/HDL-C
Triglyceride
Cholesterol/HDL-C
HDL-C
0.2
0.1
0
0.2
0.1
TG/HDL-C
Triglyceride
Cholesterol/HDL-C
HDL-C
The TG/HDLC ratio >3.5
provides a
simple
means of
identifying
insulin
resistant,
dyslipidemic
patients who
are likely to
be at
increased
risk of CVD.
0
0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
1 - Specificity
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
1 - Specificity
Receiver-operating characteristic curves of the TG/HDL cholesterol (HDL-C)
ratio, triglyceride, cholesterol/HDL cholesterol ratio, and HDL cholesterol
concentrations for prediction of insulin resistance in the (A) Stanford population,,
and (B) Berkeley defined diet population.
McLaughlin T et al Am J Cardiol 2005;96:399–404
MEtabolic SYndrome
in Active Subjects (MESYAS) study
TG/HDL-C Ratio for Predicting the First Coronary Event in Men
TG/HDL-C Ratio
5.0
4.0
3.0
3.0
2.0
Cases
Controls
0.0
Normal Weight Overweight
Mean values of the
TG/HDL-C ratio in
case and control
subjects according to
BMI categories
(p< 0.01 for
comparison between
each category of BMI
and between case
and control subjects).
Obesity
This study demonstrates the value of the TG/HDL-C ratio in primary
prevention of cardiovascular events and allowed identification of this
ratio as 1 of the main predictors of a first coronary event.
Cordero A et al. Am J Cardiol 2009;104:1393–1397
The TG/HDL-C Ratio in Adolescence and Subsequent
Weight Gain Predict NMR–Measured Lipoprotein
Subclasses in Adulthood
*
05
04
02
02
01
01
2
3
4
5
*
03
**
1
*
04
*
03
0
05
6
7
8
Odds Ratio
9
10
11 12 13 14
15 0
**
1
2
3
4
5
6
7
8
9
10
11 12
13 14
15
Odds Ratio
Odds ratio of baseline TG/HDL quintiles with upper quintile of A, small LDL and of B, large
VLDL during adulthood. The odds ratio was adjusted for sex by logistic regression.
(*P < .001, **P < .05).
Weiss R et al. 0.1016/j.jpeds.2010.07.002
LIPOPROTEIN MARKERS ASSOCIATED
WITH INSULIN RESISTANCE1,2
Insulin Resistant
Insulin Sensitive
Percentile in Reference Population
nmol/L
LARGE VLDL-P
8.2
nmol/L
SMALL LDL-P
large
20.2
nm
HDL SIZE
small
50.4
nm
LDL SIZE
high
2.7
nm
VLDL SIZE
low
830
μmol/L
LARGE HDL-P
low
large
8.7
25th
50th
75th
0.8
2.4
6.4
25th
50th
75th
110
506
75th
50th
25th
7.5
4.2
3.1
25th
50th
75th
42.1
46.3
51.9
75th
50th
25th
21.1
20.8
20.4
75th
50th
25th
9.6
9.2
8.9
25th
50th
75th
high
high
808
low
large
small
small
INSULIN RESISTANCE SCORE
0-100
LP-IR SCORE**
84
insulin sensitive
insulin resistant
100
0
** The LP-IR SCORE combines the information from the 6 lipoprotein markers to give improved prediction of insulin resistance**
These laboratory assays validated by LipoScience have not been cleared by the US Food and Drug Administration. The clinical utility
of these laboratory values has not been fully established.
1.Garvey WT et al. Diabetes 2003;532:453-462
2. Goff DC. et al. Metabolism. 2005;54:264-270
© 2009 LipoScience, Inc. All rights reserved
The Full NMR Report: Insulin Resistance
Particle Concentration and Size
HDL
Particles
Laboratory Test
HDL-P (total)
μmol/L
Percentile in Reference Population2
Result
25th (6.7)
50th (30.5)
28.6
75th (34.9)
high
38.5
Small LDL-P and LDL size are associated with
CVD risk, but not after LDL-P is taken into account
Insulin Resistant
high
Large VLDL-P
Lower CVD Risk
Higher CVD Risk
low
Previous
Results
Insulin Sensitive
75th (6.9)
50th (2.7)
< 0.7
25th (0.9)
low
< 0.7
nmol/L
Small LDL-P
high
75th (839)
50th (527)
25th (117)
low
< 90
< 90
Lipoprotein markers Associated with Insulin
Resistance and Diabetes Risk 3,4
nmol/L
low
Large HDL-P
25th (3.1)
50th (4.8)
75th (7.3)
10.3
10.3
μmol/L
VLDL Size
50.8
large
75th (52.5)
nm
HDL Size
nm
LP-IR Score*
0-100
50th (46.6)
25th (42.2)
small
50th (20.5)
75th (21.2)
large
50.8
nm
LDL Size
small
25th (20.4)
21.2
21.2
small
25th (8.9)
50th (9.2)
75th (9.6)
large
10
10
Insulin resistant
13
high
75th (63)
50th 45)
25th (28)
Insulin sensitive
13
Population Distributions of LDL-C, non-HDL-C, ApoB
and LDL-P in Framingham Offspring Study
Percentile
50th
Percentile
Cutpoint
LDL-C
Non-HDL-C
LDL-P
ApoB
(mg/dL)
(mg/dL)
(nmol/L)
(mg/dL)
2
70
83
720
54
5
78
94
850
62
10
88
104
940
69
20
100
119
1100
78
30
111
132
1220
85
40
120
143
1330
91
50
130
153
1440
97
60
139
163
1540
103
70
149
175
1670
110
80
160
187
1820
118
90
176
205
2020
130
95
191
224
2210
140
Population Distributions of LDL-C and LDL-P in Framingham Offspring
Study and the Multi-Ethnic Study of Atherosclerosis (MESA)
Percentile
LDL-C
(mg/dL)
LDL-C
(mg/dL)
LDL-P
LDL-P
(nmol/L) (nmol/L)
2nd Percentile Cutpoint
2
70
720
5
78
70
850
770
10
88
81
940
940
20
100
93
1100
1000
30
111
103
1220
1070
40
120
110
1330
1100
50
130
118
1440
1190
60
139
125
1540
1280
70
149
133
1670
1480
80
160
143
1820
1610
90
176
160
2020
1790
95
191
171
2210
1980
5th Percentile Cutpoint
20th Percentile Cutpoint
50th Percentile Cutpoint
MESA in red font
FOS in black
Framingham Heart Study
Offspring Cohort
1.00
0.98
Low LDL-P
0.96
Low LDL-C
n=1249
0.94
Probability of Event Free Survival
Event-free survival among participants
with low-density lipoprotein cholesterol
(LDL-C) and LDL particle number
(LDL-P) above or below the median.
Low LDL-P
0.92
0.90
Median values were 131 mg/dL for
LDL-C and 1414 nmol/L for LDL-P.
High LDL-C
n=284
0.88
0.86
Significant
LDL-C / LDL-P
discordance
High LDL-P
High LDL-C
n=1251
0.84
LDL-P was strongly associated
with increased CVD risk in both
men and women (p<0.0001)
High LDL-P
0.82
Low LDL-C
n=282
When data for men and women
were combined,
LDL-P was approximately twice
as strongly related to CVD
incidence as LDL-C
0.80
0.78
Particle number (LDL-P) is
the key risk factor
0.76
0.74
0
2
4
6
8
10
12
14
16
Years of Follow-up
Cromwell W et al. J Clin Lipidol 2007;1:583-592
Multi-Ethnic Study of Atherosclerosis (MESA) LDL-C vs LDL-P Discordance
91
100
141
157
90
1680
80
1510
70
1400
60
1310
50
1140
40
1060
30
960
840
20
10
0
79
91
100 108 116 123
LDL-C percentile
132
141
157
Otvos JD et al. Journal of Clinical Lipidology (2011) 5, 105–113
LDL-P (nmol/L)
LDL-P percentile
79
LDL-C (mg/dL)
108 116 123 132
NLA Expert Panel
Advice
LDL Particle
Concentration (LDL-P)
Relations between
LDL-C and LDL-P
among 5598 MESA
participants.
Relation of LDL-C
and LDL-P levels
given in percentile
units.
The dashed lines
bracket concordant
LDL-C and LDL-P
values defined as
those within 612
percentile units.
LDL-cholesterol
LDL cholesterol (LDL-C) is the cholesterol trafficked within all of the
low and intermediate density lipoproteins in a deciliter of plasma
Intermediate
Density
Lipoprotein (IDL)
IDL-C
Low Density
Lipoprotein (LDL)
+
Actual LDL-C
Lipoprotein (a)
+
Lp(a)-C
Evaluating LDL Size
LDL size is measured in nanometers (nm) or Angstroms (A0)

23.0 – 20.6 nm
Large
(Pattern A)


20.5 – 18.0 nm

Small
(Pattern B)
►LDL-size
Very large, Large, Small

Average diameter (nm) of
the patient’s LDL
particles.
A predominance of small
LDL particles is
associated with metabolic
syndrome and insulin
resistance
Small LDLs traffic LpPLA2
Small LDLs are more
prone to glycation and
oxidation
Small LDLs are less
readily cleared by LDL
receptors
Gel Electrophoresis Lipoprotein Separation
VLDL
LDL
HDL
Small, dense
LDL
Large,
buoyant LDL
LDL is a group of lipoproteins
with density ranging from 1.019
to 1.063 g/mL which can be
further divided in subclass
fractions.
Small LDL (sdLDL) is one
subfraction with a smaller
particle size and higher density
Small, dense
LDL
d = 1.044
25.5 nm
Large
Light
Size
Small
Density
Heavy
Ito Y Fats of Life 2001;XXV (3):9-13
LDL Sizing by 3 Segmented NonLinear Gradient Gel Electrophoresis
LDL-S3GGE™
.81
1
.59
2
3
4 5
6
7
233.12
217.6
IVa
IVb
.44
.33
.24
.16
.10
.05
359.44
341.71
323.98
303.70
281.98
263.86
I
247.37
IIa IIb IIIa+b
Large, Buoyant
Small, dense
Segmented LDL Subclass Determination
LDL Particle Composition
Normal core
lipid content
Cholesterol depleted,
TG enriched core
Normal core
lipid content
Cholesterol depleted,
TG enriched core
Pattern B
Pattern A
Less cholesterol per particle than normal
# of cholesterol
molecules per
LDL-particle
►
►
►
►
2600
2150
2150
1700
LDL particles differ in diameter by about 12% or 3 nm
LDL particle composition also varies considerably among patients with a
normal CE/TG ratio being 4.0
The number of cholesterol molecules per particle is influenced by LDL
particle size, core CE/TG ratio or both
The more cholesterol-depleted an LDL particle is, the more will be required
to traffic a given level of LDL-C