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Lipoproteins Lipoproteins
)Classes
)Composition:
) Chylomicrons
)Phospholipid, free cholesterol & protein on surface and a ) Very-low-density (VLDL)
core made up of primarily triglyceride & cholesterol
) Intermediate density lipoprotein (IDL)
esters
) Low-density (LDL)
)Apolipoproteins are proteins on the surface which
) High-density (HDL)
regulate their transport and metabolism
)Significance
) Apo A
) Premature coronary artery disease (CAD)
) Apo B
) Pancreatitis (hypertriglyceridemia)
)Function of Cholesterol and role of lipoproteins: (VLDL + IDL + LDL-C) = non HDL-C Apo B particles
Cell membranes, bile acid synthesis, steroid
hormone precursor
Low HDL-C as a Potent Predictor of CHD
)Although strong epidemiological evidence that HDL-C protects
against CHD exists, there has not been a cause and effect
relationship proved
)From analysis of 4 epi trials, for each 1mg/dL increase in HDL-
C, a 2% decrease in CHD risk in men and 3% decrease in
women may occur
) 11% of US men have isolated Low HDL-C levels (NHANES III), but up to
17-36% of high risk pts.
)LDL-C management does not completely remove the risk
imparted by low HDL-C
Risk of CHD by HDL and LDL Levels: Lipoprotein & Lipid Concentrations
Framingham Heart Study ApoB-
ApoB-lipoproteins ApoAI-
ApoAI-lipoproteins
D
CH
of
isk
R
V6 V5 V4 V3 V2 V1 L3 L2 L1 H5 H4 H3 H2 H1
el.
R
IDL-C + LDL-
LDL-C HDL-
HDL-C
)
3x VLDL-
VLDL-C IDL-
/L
25 (0.65)
ol
0.5
m
2x
(m
45 (1.16) (TG/5)
1x Reported LDL-
LDL-C
dl
g/
65 (1.68)
m
Total Cholesterol
,
-C
85 (2.20)
DL
TC =Non
LDLHDL-
LDL--C + -HDL-
HDL C = TC
HDL -C + VLDL-
HDL-
HDL-C
VLDL-C
H
Coronary Remodeling
Lipid-Rich Plaque
Progression
Expansion overcome:
Compensatory expansion lumen narrows
maintains constant lumen
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. All of these listings are associated with >20% risk of a CHD event in 10 years
JAMA. 2001;285:2486-2497. LDL-C goal is < 100mg/dL
Patients With Diabetes Are at Even Greater Step #3 Determine Major CHD Risk Factors
Risk for CHD
Other Than LDL-C According to ATP-III
Patients With Diabetes Without History of CHD Have Incidence of MI
Comparable to Patients Without Diabetes With CHD History
Positive risk factors
50% 45% ) Age ) Cigarette smoking
) Men 45 ) Hypertension: BP 140/90 mm
Diabetes Women 55 Hg or on antihypertensive
40% )
No diabetes ) Family history of premature CHD medication
7-Year MI 30% (first-degree relative) ) Low HDL-C: <40 mg/dL
Incidence, ) Male relative age <55 years
% 20.2%
18.8% ) Female relative age <65 years
20%
N=2,432
Step #4 Framingham Point Scale for Estimating 10-Year Patient Risk Categories Based on
CHD Risk if > 2 risk factors (Men/Women)
Age Total cholesterol HDL-C the 10-year Risk Assessment
20 34 = -9/-7 Age Age Age Age Age 60 = -1/-1
35 39 = -4/-3 2039 4049 5059 6069 7079 50 59 = 0/0
40 44 = 0/0 <160 0/0 0/0 0/0 0/0 0/0 40 49 = 1/1
45 49 = 3/3 160 199 4/4 3/3 2/2 1/1 0/1 <40 = 2/2
50 54 =
55 59 =
6/6
8/8
200 239 7/8
240 279 9/11
5/6
6/8
3/4
4/5
1/2
2/3
0/1
1/2 >20% High risk risk equivalent
60 64 = 10/10 280 11/13 8/10 5/7 3/4 1/2
65 69 = 11/12
Systolic blood pressure Smoker
70 74 = 12/14
If Untreated If Treated Age Age Age Age Age
75 79 = 13/16
<120 0/0 0/0
120 129 0/1 1/3
2039 4049 5059 6069 7079
No 0/0 0/0 0/0 0/0 0/0 10% 20% Moderate risk
130 139 1/2 2/4 Yes 8/9 5/7 3/4 1/2 1/1
140 159 1/3 2/5
160 2/4 3/6
Total points:
10-year CHD
<0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 >17
<10% Low risk
risk (%) for men: <1 1 1 1 1 1 2 2 3 4 5 6 8 10 12 16 20 25 30
Total points: <9 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
10-year CHD
risk (%) for women: <1 1 1 1 1 2 2 3 4 5 6 8 11 14 17 22 27 30 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:24862497.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:24862497.
Step #5 Establish Risk Category and Implications of Recent Clinical Trials for the
Determine Goal: National Cholesterol Education Program Adult
LDL-C Level
LDL-C Level for
Treatment Panel III Guidelines
Risk LDL-C Goal for Initiation
Consideration of
Category (mg/dL) of TLC Scott M. Grundy, James I. Cleeman,C. Noel Bairey
Drug Therapy (mg/dL)
(mg/dL) Merz, H. Bryan Brewer, Jr, Luther T. Clark, Donald
B. Hunninghake, Richard C. Pasternak, Sidney C.
CHD or CHD risk
130 Smith, Jr, Neil J. Stone
equivalents <100 100
(100-129: drug optional)
(10-y risk >20%) For the Coordinating Committee of the National
Cholesterol Education Program
2+ Risk factors (10- 130: 10-y risk 10%-20%
<130 130
y risk <20%*) 160: 10-y risk <10%
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Grundy SM et al. Circulation; available at JAMA. 2001;285:24862497.
http://circ.ahajournals.org
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:2486-2497. JAMA. 2001;285:2486-2497.
*Updated based on Grundy et al, Circulation 2005;112:2735-2752
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:2486-2497.
Relative Risk of Death in Patients With Metabolic
Syndrome Compared With Those Without Metabolic Step # 9 Treat Elevated Triglycerides
Syndrome
CHD mortality
4.0
CVD mortality Classification of Serum Triglycerides
3.5 All-cause mortality
2.5
* ) High 200499 mg/dL
2.0 *
1.5
) Very high 500 mg/dL
1.0
) Primary aim to lower LDL-C
0.5
) Intensify weight management, increase physical
0.0
NCEP NCEP WHO WHO activity, if LDL target is reached and TG still exceed
Waist >102 cm Waist >94 cm WHR >0.90 or Waist 94 cm 200mg/dL, then set secondary goal for non-HDL
BMI 30
*P<.05.
Fewer Particles More Particles ) Those with TG 200-499 mg/dL: achieve non-HDL-C
goal* as secondary priority
Correlates with: Correlates with:
TC 198 mg/dL TC 210 mg/dL ) Those with TG <200 mg/dL: consider drugs for raising
LDL-C 130 mg/dL LDL-C 130 mg/dL HDL-C (fibrates, niacin)
TG 90 mg/dL TG 250 mg/dL
HDL-C 50 mg/dL HDL-C 30 mg/dL
Non-HDL-C 148 mg/dL Non-HDL-C 180 mg/dL
* Non-HDL-C goal is set at 30 mg/dL higher than LDL-C goal.
Otvos JD, et al. Am J Cardiol. 2002;90:22i-29i. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:2486-2497.
Framingham Point Scale for Estimating 10-Year
Patient Case CHD Risk (Men/Women)
Age Total cholesterol HDL-C
20 34 = -9/-7 Age Age Age Age Age 60 = -1/-1
35 39 = -4/-3 2039 4049 5059 6069 7079 50 59 = 0/0
) 53 yo WM 61, 210 lbs (95.5Kg) waist 40 44 = 0/0 <160 0/0 0/0 0/0 0/0 0/0 40 49 = 1/1
circumference 40 with a BMI 27.7kg/sqm with a 45 49 =
50 54 =
3/3
6/6
160 199 4/4
200 239 7/8
3/3
5/6
2/2
3/4
1/1
1/2
0/1
0/1
<40 = 2/2
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:24862497. JAMA. 2001;285:2486-2497.
Formulas
Friedwalls Equation for calculating LDL-C:
( LDL ) = ( Total - HDL ) - ( TRG / 5 )
Note: not useful or accurate if Trigs exceed 400mg/dL
Eg: T-Chol=240mg/dL, HDL=50mg/dL, TG= 150mg/dL what is LDL-C?
Answer: (240-50)-(150/5)=160mg/dL
Units:
-Traditional -- mg / dL
-SI -- mmol / L
Conversion: (mg / dL) x 0.02586 = (mmol / L)
eg. 100mg/dL x 0.02586 = 2.59