1

2 The Good, Bad, Ugly and Deadly

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

4 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 OptimalBorderlineHigh risk LDL C <100130– HDL C >6035–45<35 Triglycerides <150150–199>200 Total Choles. <200200–239>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

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 + H 2 O 2 phosphate H 2 O aminophenazone+ESPA Quinoneimine Principle: Enzymatic Method Lipoprotein lipase glycerolkinase glycerolphosphate oxidase peroxidase

Triglycerides TG LevelClassificationTreatment < 150 mg%Normal TGNo Rx. 150 to 200 mg%Borderline highDiet alone 201 to 500 mg%HighDiet + drugs > 500 mg%Very highDiet + Intensive care 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.

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.

Discussion Interpretation 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 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 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 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 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 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 High Lipoprotein(a) : ↓ HDL, ↑ TG, 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 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