2. The Good, Bad, Ugly and Deadly

3. Two Types of Lipids

4. Composition of Lipoprotein

5. Lipoproteins Apoprotein boat Apo A I and A II for HDL Apo B100 for LDL
classification  based on the relative densities of the aggregates on ultracentrifugation
Lipoproteins TG EC
Apoprotein boat
Apo A I and A II for HDL Apo B100 for LDL
Apo B100+C+E for VLDL, IDL Apo B100+Apo(a) for Lp(a)

6. Good, Bad, Ugly & Deadly HDL LDL VLDL Lp(a) TG C GOOD BAD C UGLY
A I, A II
HDL
LDL
GOOD
BAD C TG
B 100
VLDL
Lp(a)
UGLY
DEADLY C TG
B E +C TG C TG
B 100+ (a)

7. All are the terrorists !! Measurements Apolipoprotein B Non-HDL-C
TG-rich lipoproteins
VLDL
VLDLR
IDL
LDL
SDL
Highly atherogenic

8. Lipid Profile Report PP
Fasting

9. Normal Lipid Profile Total Cholesterol < 200
TG ‘Ugly’ Lipid < 150
‘Bad’ Cholesterols LDL < 100
HDL ‘Good’ cholesterol > 50
VLDL is Ugly TG ÷ 5 < 30
Lp(a) ‘Deadly’ cholesterol < 20

10. Normal range Element Optimal Borderline High risk LDL C <100
130–159
160+
HDL C
>60
35–45
<35
Triglycerides
<150
150–199
>200
Total Choles.
<200
200–239
>240

11. Cholesterol

12. Specimen Serum, Plasma (EDTA, Heparin)
Certain anticoagulants, such as fluoride, citrate, and oxalate, cause large shifts of water from the red blood cells to the plasma, which result in the dilution of plasma components.
Storage and Stability
7 days at 20 – 25 °C
7 days at 4 – 8 °C
3 months at -20 °C

13. Principle: Enzymatic Reaction
Determination of cholesterol after enzymatic hydrolysis and oxidation.
The colorimetric indicator is quinoneimine which is generated from 4-aminoantipyrine and hydroxybenzoate by hydrogen peroxide under the catalytic action of peroxidase
Cholesterol Esterase
Cholesterol oxidase
Peroxidase

14. Linearity
Dilution
Source of errors

15. Triglycerides

16. Specimen Serum Plasma (EDTA) or heparin
Certain anticoagulants, such as fluoride, citrate, and oxalate, cause large shifts of water from the red blood cells to the plasma, which result in the dilution of plasma components.
Fasting sample (from 12 to 16 h) is essential for triglyceride analysis
Storage and stability

17. Principle: Enzymatic Method
Triglycerides Glycerol + 3 fatty acids
Glycerol + ATP Glycerol-3 phosphate + ADP
Glycerol-3 phosphate dihydroxyacetone + H2O phosphate
H2O2 + 4-aminophenazone+ESPA Quinoneimine
Lipoprotein lipase
glycerolkinase
glycerolphosphate oxidase
peroxidase

18. Linearity
Dilution
Source of errors

19. NCEP 2004 Guidelines by expert panel on TG
Triglycerides
TG Level
Classification
Treatment
< 150 mg%
Normal TG
No Rx.
150 to 200 mg%
Borderline high
Diet alone
201 to 500 mg%
High
Diet + drugs
> 500 mg%
Very high
Diet + Intensive Rx
NCEP 2004 Guidelines by expert panel on TG

20. HDL HDL is a fraction of plasma lipoproteins
It is composed of 50% protein, 25% phospholipid, 20% cholesterol, and 5% triglycerides
Evidence suggests that high-density lipoprotein (HDL) cholesterol is cardioprotective.
LDL-chol = [Total chol] - [HDL-chol] - ([TG]/2.2) where all concentrations are given in mmol/L
(note that if calculated using all concentrations in mg/dL then the equation is [LDL-chol] = [Total chol] - [HDL-chol] - ([TG]/5))

21. Limitations of the Friedewald equation
The Friedewald equation should not be used under the following circumstances:
when chylomicrons are present.
when plasma triglyceride concentration exceeds 400 mg/dL (4.52 mmol/L).
in patients with type III hyperlipoproteinemia.

22. TC, TGs, and HDL cholesterol are measured directly; TC and TG values reflect cholesterol and TGs in all circulating lipoproteins, including chylomicrons, VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL. TC values vary by 10% and TGs by up to 25% day-to-day even in the absence of a disorder. TC and HDL cholesterol can be measured in the nonfasting state, but most patients should have all lipids measured while fasting for maximum accuracy and consistency.
Patients with an extensive family history of heart disease should also be screened by measuring Lp(a) levels.

23. Testing should be postponed until after resolution of acute illness, because TGs increase and cholesterol levels decrease in inflammatory states. Lipid profiles can vary for about 30 days after an acute MI; however, results obtained within 24 h after MI are usually reliable enough to guide initial lipid-lowering therapy.

24. LDL cholesterol values are most often calculated as the amount of cholesterol not contained in HDL and VLDL. VLDL is estimated by TG ÷ 5 because the cholesterol concentration in VLDL particles is usually 1/5 of the total lipid in the particle. Thus, LDL cholesterol = TC − [HDL cholesterol + (TGs ÷ 5)] (Friedewald formula). This calculation is valid only when TGs are < 400 mg/dL and patients are fasting, because eating increases TGs. The calculated LDL cholesterol value incorporates measures of all non-HDL, nonchylomicron cholesterol, including that in IDL and lipoprotein (a) [Lp(a)]..

25. LDL can also be measured directly using plasma ultracentrifugation, which separates chylomicrons and VLDL fractions from HDL and LDL, and by an immunoassay method. Direct measurement may be useful in some patients with elevated TGs, but these direct measurements are not routinely necessary. The role of apo B testing is under study because values reflect all non-HDL cholesterol (in VLDL, VLDL remnants, IDL, and LDL) and may be more predictive of CAD risk than LDL alone.

26. Interpretation of Results
Discussion
Interpretation of Results

27. How to interpret Lipid Profile Report?
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides
200 50
150
100 20 30
150
Normal Lipid Profile

28. Interpret this Lipid Profile Report
240
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides 50
190
140 20 30
150
Hyper cholesterolimia ↑LDL, HDL, TG, Lp(a) - N

29. Interpret this Lipid Profile Report
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides
200 50
150 70 20 60
300
Hyper triglyceridemia ↑TG, HDL, LDL, Lp(a) - N

30. Interpret this Lipid Profile Report
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides
160 25
135 85 20 30
150
Low HDL : ↓HDL, LDL, TG, Lp(a) - N

31. Interpret this Lipid Profile Report
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides
200 45
155 75 50 30
150
High Lipoprotein(a) : ↑Lp(a) , HDL, LDL, TG - N

32. Interpret this Lipid Profile Report
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides
200 25
175 95 20 60
300
High Lipoprotein(a) : ↓HDL, ↑TG, LDL, Lp(a) - N

33. Interpret this Lipid Profile Report
260
Total Cholesterol
HDL Cholesterol (Soldiers) - Good
Non HDL Cholesterol (Culprits)
LDL Cholesterol – Bad fellows
Lipoprotein(a) – Deadly fellows
VLDL Cholesterol (1/5 of TG)- Ugly
B. Triglycerides 50
210
120 40 50
250
Combined Dyslipidemia : ↑ TC↑LDL↑TG ↑Lp(a)

34. J. Atherosclerosis : Hopkins PN, 1997 – 17, 2792
Look at the risks
Low HDL + High LDL
LP(a) excess > 30 mg% +
LP(a) excess > 30 mg% + LDL high ++
LP(a) excess > 30 mg% + low HDL +++
LP(a) excess > 30 mg% + Incr. tHCy
LP(a) excess + Incr. tHCy + low HDL
Circulating lipids are one aspects
Tissue lipid content is more important
J. Atherosclerosis : Hopkins PN, 1997 – 17, 2792

35. Dyslipidemia
is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein level that contributes to the development of atherosclerosis. Causes may be primary (genetic) or secondary. Diagnosis is by measuring plasma levels of total cholesterol, TGs, and individual lipoproteins. Treatment is dietary changes, exercise, and lipid-lowering drugs.

36. Case Study #1
47 year-old man who is overweight (BMI 29) and who reports he frequently eats out, often at fast food places.
What assessment tests would you recommend?

37. He is noted to have a blood pressure of 144/86 mmHg (average of two tests) and a fasting blood sugar of 115 mg/dl
His lipid profile shows an LDL-C of 162 mg/dl and an HDL-C of 36 mg/dl, with a triglycerides of 175 mg/dl.
What should the approach to treatment be and goals proposed?

38. Case Study #2
A 28-year old female has been diagnosed by a physician with diabetes.
What assessment tests would you order?

39. A blood pressure of 134/82 mmHg is noted (mean of two measures)
A fasting lipid profile shows an HDL-C of 40 mg/dl and LDL-C of 140 mg/dl is noted, with triglycerides of 260 mg/dl.
What should the approach to treatment be?

40. Case Study #3
A 64-year old woman is admitted to the hospital and diagnosed with a myocardial infarction. She reports a history and has been on treatment for hypertension with.
What assessments should be performed?

41. A fasting lipid profile done 12 hours after admission shows an LDL-C of 125 mg/dl, HDL-C of 30 mg/dl, and triglycerides of 150 mg/dl
Any other recommendations for treatment?

42. Clinical Action For all above 20 years once in every 5 years
For those above 45 yrs – once in 2 years
For those with already known lipid abnormality follow-up every 3-6 months
Extended Lipid profile includes Homocysteine, LP(a), SD-LDL, ALP, Apo A and Apo B, hS-CRP

43. There is no natural cutoff between normal and abnormal lipid levels because lipid measurements are continuous
A linear relation probably exists between lipid levels and cardiovascular risk
elevated TG and low HDL levels are more predictive of cardiovascular risk in women than in men
HDL levels do not always predict cardiovascular risk. High HDL levels caused by some genetic disorders may not protect against cardiovascular disorders, and low HDL levels caused by some genetic disorders may not increase the risk of cardiovascular disorders.

44. Proof of treatment benefit is strongest for lowering elevated low-density lipoprotein (LDL) levels. In the overall population, evidence is less strong for a benefit from lowering elevated TG and increasing low high-density lipoprotein (HDL) levels, in part because elevated TG and low HDL levels are more predictive of cardiovascular risk in women than in men