Dyslipidemia update by Dr Sarma

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(No Transcript)
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The Good, Bad, Ugly and Deadly
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Two Types of Lipids
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Composition of Lipoprotein
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Lipoproteins
classification  based on the relative densities
of the aggregates on ultracentrifugation
Apo A I and A II for HDL Apo B100 for LDL Apo
B100CE for VLDL, IDL Apo B100Apo(a) for Lp(a)
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Good, Bad, Ugly Deadly
LDL
GOOD
BAD
VLDL
Lp(a)
UGLY
DEADLY
TG
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All are the terrorists !!
Highly atherogenic
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Lipid Profile Report
PP
Fasting
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Normal Lipid Profile

• Total Cholesterol lt 200
• TG Ugly Lipid lt 150
• Bad Cholesterols LDL lt 100
• HDL Good cholesterol gt 50
• VLDL is Ugly TG 5 lt 30
• Lp(a) Deadly cholesterol lt 20

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Normal range
Element Optimal Borderline High risk
LDL C lt100 130159 160
HDL C gt60 3545 lt35
Triglycerides lt150 150199 gt200
Total Choles. lt200 200239 gt240
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Cholesterol
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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

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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
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• Linearity
• Dilution
• Source of errors

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Triglycerides
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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

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Principle Enzymatic Method

• Triglycerides Glycerol 3 fatty acids
• Glycerol ATP Glycerol-3 phosphate ADP
• Glycerol-3 phosphate dihydroxyacetone
  H2O2 phosphate
• H2O2 4-aminophenazoneESPA
  Quinoneimine

Lipoprotein lipase
glycerolkinase
glycerolphosphate oxidase
peroxidase
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• Linearity
• Dilution
• Source of errors

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Triglycerides
TG Level Classification Treatment
lt 150 mg Normal TG No Rx.
150 to 200 mg Borderline high Diet alone
201 to 500 mg High Diet drugs
gt 500 mg Very high Diet Intensive Rx
NCEP 2004 Guidelines by expert panel on TG
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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))

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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.

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• 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.

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• 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.

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• 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 lt 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)..

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• 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.

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Discussion Interpretation of Results
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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
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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
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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
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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
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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
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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
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Interpret this Lipid Profile Report
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• 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)
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Look at the risks

• Low HDL High LDL
• LP(a) excess gt 30 mg
• LP(a) excess gt 30 mg LDL high
• LP(a) excess gt 30 mg low HDL
• LP(a) excess gt 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

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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.

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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?

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• 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?

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Case Study 2

• A 28-year old female has been diagnosed by a
  physician with diabetes.
• What assessment tests would you order?

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• 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?

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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?

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• 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?

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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

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• 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.

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• 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