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www.drsarma.in
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The Good, Bad, Ugly and Deadly
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Two Types of Lipids
LIPIDS IN BLOOD
TOTAL CHOLESTEROL TRIGLYCERIDES (TG)
GOOD CHOLESTEROLHDL 1 and HDL 2
BAD CHOLESTEROLLDL, VLDL (TG), Lp(a)
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Composition of
Lipoprotein
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Lipoproteins
ECTG
Apoprotein boat
Apo A I and A II for HDL Apo B100 for LDLApo B100+C+E for VLDL, IDL Apo B100+Apo(a) for Lp(a)
classification based on the relative
densities of the aggregates on
ultracentrifugation
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Good, Bad, Ugly & Deadly
CTG
B 100 + E +C
CTG
B 100
CTG
A I, A II
HDL LDL
VLDL
CTG
B 100+ (a)
Lp(a)TG
GOOD BAD
UGLY DEADLY
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All are the terrorists !!
Apolipoprotein BApolipoprotein B
Non-HDL-CNon-HDL-CMeasurementsMeasurements
TG-rich lipoproteinsTG-rich lipoproteins
VLDLVLDL VLDLRVLDLR IDLIDL LDLLDL SDLSDL
Highly atherogenic
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LIPIDS ESTIMATED
TOTAL CHOLESTEROL (TC) TRIGLYCERIDES (TG)
HDLc LDLc VLDLc Chylomicrons VLDL
Lipid Profile Report
PP Fasting
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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
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
Cholesterol
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 °C7 days at 4 – 8 °C3 months at -20 °C
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
• Linearity• Dilution• Source of errors
Triglycerides
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
• Triglycerides Glycerol + 3 fatty acids
• Glycerol + ATP Glycerol-3 phosphate + ADP
• Glycerol-3 phosphate dihydroxyacetone + H2O2 phosphate
• H2O2 + 4-aminophenazone+ESPA Quinoneimine
Principle: Enzymatic Method
Lipoprotein lipase
glycerolkinase
glycerolphosphate oxidase
peroxidase
• Linearity• Dilution• Source of errors
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
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))
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.
• 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.
• 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.
• 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)]..
• 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.
DiscussionInterpretation of Results
How to interpret Lipid Profile Report?
A. 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 150
100
150
50
200
20
30
Normal Lipid Profile
Interpret this Lipid Profile Report
A. 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 150
140
190
50
240
20
30
Hyper cholesterolimia ↑LDL, HDL, TG, Lp(a) - N
A. 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 300
70
150 50
200
20
60
Hyper triglyceridemia ↑TG, HDL, LDL, Lp(a) - N
Interpret this Lipid Profile Report
A. 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 150
85
135 25
160
20
30
Low HDL : ↓HDL, LDL, TG, Lp(a) - N
Interpret this Lipid Profile Report
A. 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 150
75
155 45
200
50
30
High Lipoprotein(a) : ↑Lp(a) , HDL, LDL, TG - N
Interpret this Lipid Profile Report
A. 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 300
95
175 25
200
20
60
High Lipoprotein(a) : ↓HDL, ↑TG, LDL, Lp(a) - N
Interpret this Lipid Profile Report
Interpret this Lipid Profile Report
A. 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 250
120
210
50
260
40
50
Combined Dyslipidemia : ↑ TC↑LDL↑TG ↑Lp(a)
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
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.
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?
• 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?
Case Study #2
• A 28-year old female has been diagnosed by a
physician with diabetes.
• What assessment tests would you order?
• 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?
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?
• 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?
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
• 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.
• 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
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