1 www drsarma in 2 The Good Bad

1 www. drsarma. in

2 The Good, Bad, Ugly and Deadly

3 Two Types of Lipids LIPIDS IN BLOOD TOTAL CHOLESTEROL GOOD CHOLESTEROL HDL 1 and HDL 2 TRIGLYCERIDES (TG) BAD CHOLESTEROL LDL, VLDL (TG), Lp(a)

4 Composition of Lipoprotein

Lipoproteins TG 5 classification based on the relative densities of the aggregates on ultracentrifugation E C Apoprotein boat Apo A I and A II for HDL LDL Apo B 100+C+E for VLDL, IDL B 100+Apo(a) for Lp(a) Apo B 100 for Apo

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

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

8 Lipid Profile Report LIPIDS ESTIMATED TOTAL CHOLESTEROL (TC) HDLc LDLc VLDLc TRIGLYCERIDES (TG) Chylomicrons PP VLDL Fastin g

9 Normal Lipid Profile • Total Cholesterol 200 • TG ‘Ugly’ Lipid 150 • ‘Bad’ Cholesterols LDL 100 • HDL ‘Good’ cholesterol 50 • VLDL is Ugly TG ÷ 5 < < < > <

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

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 Ø 7 days at 20 – 25 °C Ø 7 days at 4 – 8 °C Ø 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 + ATP Lipoprotein lipase glycerolkinase Glycerol + 3 fatty acids Glycerol-3 phosphate + ADP glycerolphosphate oxidase • Glycerol-3 phosphate H 2 O 2 • H 2 O 2 + 4 -aminophenazone+ESPA dihydroxyacetone + phosphate peroxidase Quinoneimine

• 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% > 500 mg% High Diet + drugs 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/d. L 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: Øwhen chylomicrons are present. Øwhen plasma triglyceride concentration exceeds 400 mg/d. L (4. 52 mmol/L). Øin 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 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/d. L 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.

Discussion Interpretation of Results

How to interpret Lipid Profile Report? A. Total Cholesterol 200 HDL Cholesterol (Soldiers) - 50 Good 150 Non HDL Cholesterol (Culprits) 10 0 20 LDL Cholesterol – Bad fellows 30 Lipoprotein(a) – Deadly fellows 150 VLDL Cholesterol (1/5 of TG)- Ugly Normal Lipid Profile

Interpret this Lipid Profile Report A. Total Cholesterol 240 HDL Cholesterol (Soldiers) - 50 Good 190 Non HDL Cholesterol (Culprits) 14 0 20 LDL Cholesterol – Bad fellows 30 Lipoprotein(a) – Deadly fellows 150 VLDL Cholesterol (1/5 of TG)- Ugly Hyper cholesterolimia ↑LDL, HDL, TG, Lp(a) - N

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

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

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

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

Interpret this Lipid Profile Report A. Total Cholesterol 260 HDL Cholesterol (Soldiers) - 50 Good 210 Non HDL Cholesterol (Culprits) 12 0 40 LDL Cholesterol – Bad fellows 50 Lipoprotein(a) – Deadly fellows 250 VLDL Cholesterol (1/5 of TG)- Ugly Combined Dyslipidemia : ↑ TC↑LDL↑TG ↑Lp(a)

Look at the risks • Low HDL + High LDL + • LP(a) excess > 30 mg% + LDL high ++ • LP(a) excess > 30 mg% + low HDL +++ • LP(a) excess > 30 mg% + Incr. t. HCy ++++ • LP(a) excess + Incr. t. HCy + low HDL

Dyslipidemia • is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low highdensity 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 mm. Hg (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 mm. Hg 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, h. S-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