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The Good, Bad, Ugly and Deadly

Two Types of Lipids

Composition of Lipoprotein

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)

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 100 + E +C TG C TG B 100+ (a)

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

Lipid Profile Report PP Fasting

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 °C 7 days at 4 – 8 °C 3 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

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

Linearity Dilution Source of errors

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

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.

Interpretation of Results Discussion Interpretation of Results

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

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

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

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

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

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

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)

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

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