dyslipidemia update by dr sarma

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    www.drsarma.in

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    O ALMIGHTY

    Tallee ninnu dalanchi pustakamu

    chaetan boonitin neevu naa

    ullambanduna nilchi jrumbhanamugaan

    uktul su sabdambul

    sobhillan balkumu naadu vaakkunan

    sampreetin, Jaganmohinee

    pullaabjaakshee Saraswatee Bhagavatee

    poornaendu bimbaanana

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    O! Almighty, the Goddess of Wisdom!

    We start this learning process, keeping

    YOU in our inner hearts, please shower

    Your kind blessings on all of us and ensure

    What ever we speak is eloquent

    What ever we discuss is pertinent

    What ever we learn is relevant.

    May we be blessed with the best wisdom !

    O! ALMIGHTY

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    Dr.Sarma RVSN, M.D., M.Sc (Canada)Consultant in Medicine and Chest,

    # 3, Jayanagar, Tiruvallur 602 001

    98940 60593, 2766 0593

    Visit us at : www.drsarma.in

    Dyslipidemias-Practice Approach

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    CD ROM Available

    The contents of my todays presentations

    are made available in a CD-ROM format

    This CD, in addition, contains my talks on

    Asthma, COPD, Hypertension, ECG, CAD

    Dyslipidemias, Diabetes, Osteoporosis

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    [email protected] 6

    The Almighty

    Pardons and Grants me heaven

    Even if I don't know a single letter about

    Crutz Feld Jacobs Disease

    Tsutsugamushi Fever

    Criggler Nazzar Syndrome

    South American equine encephalitis and

    Many and much more rarer topicsBUT .

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    [email protected] 7

    The Almighty

    Will drag me to hell and will not pardon

    My ignorance of even the minute details of HT, DM

    My indifference to apply the current knowledge

    My negligence in screening for Lipids, DM, HT, LVH

    My despondency about preventing TOD and ACS

    My inadequacy in maintaining my patients

    Normotensive, Euglycemic, Eulipidemic

    (This is applicable to all common diseases)

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    National Cholesterol

    Education Program -NCEP

    Adult Treatment Panel III(ATP III) Guidelines -2002

    Updated October 2004

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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 CHOLESTEROL

    HDL 1 and HDL 2

    BAD CHOLESTEROL

    LDL, VLDL (TG), Lp(a)

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    Lipoprotein

    TG, EC

    Phospholipids

    Free Cholesterol

    (Hydrophilic)

    Apoproteins A,

    B, C, E, (a)

    (Amphiphatic)

    Lipids or Fats

    (Hydrophobic)Size < RBC

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    Good, Bad, Ugly & Deadly

    CTG

    B 100 + E +C

    CTG

    B 100

    CT

    GA 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 B

    Non-HDL-CMeasurements

    TG-rich lipoproteins

    VLDL VLDLR IDL LDL SDL

    Highly atherogenic

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    Particle size & Density

    Chylomicrons

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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

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    How to interpret Lipid Profile Report?

    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 150

    100150

    50

    200

    20

    30

    Normal Lipid Profile

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    Interpret this Lipid Profile Report

    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)

    LDL CholesterolBad 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

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    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 300

    70150

    50

    200

    20

    60

    Hyper triglyceridemia TG,HDL, LDL, Lp(a) - N

    Interpret this Lipid Profile Report

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    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 150

    85135

    25

    160

    20

    30

    Low HDL :HDL,LDL, TG, Lp(a) - N

    Interpret this Lipid Profile Report

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    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 150

    75155

    45

    200

    50

    30

    High Lipoprotein(a) :Lp(a),HDL, LDL, TG - N

    Interpret this Lipid Profile Report

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    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 300

    95175

    25

    200

    20

    60

    High Lipoprotein(a) :HDL,TG, LDL, Lp(a) - N

    Interpret this Lipid Profile Report

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    Interpret this Lipid Profile Report

    A. Total Cholesterol

    HDL Cholesterol (Soldiers) - Good

    Non HDL Cholesterol(Culprits)

    LDL CholesterolBad fellows

    Lipoprotein(a)Deadly fellows

    VLDL Cholesterol (1/5 of TG)- Ugly

    B. Triglycerides 250

    120

    210

    50

    260

    40

    50

    Combined Dyslipidemia : TCLDLTG Lp(a)

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    Dyslipidemic Triad

    A. Isolated High LDL 32.90%

    B. Isolated low HDL 21.35%

    C. Isolated high TG 10.45%

    IHJ, 2000, 52: 173-177

    Am J Med, 1998, vol 105(1A), 48S-56S

    LDL

    HDL

    TG

    The Triad

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    Indian Dyslipidemic Triad

    IHJ, 2000, 52: 173-177

    Am J Med, 1998, vol 105(1A), 48S-56S

    Lp(a)

    HDL

    TG

    The Indian Triad

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    Indian Dyslipidemia

    Low HDL 39.2%

    High TG 32.5%

    Lp(a) excess 28.6%

    High LDL 10.8%

    Normal Lipids 23.5%

    Am J C 2001;88(suppl) 9N-13N; 22N

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    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 lipidsare one aspects Tissue lipidcontent is more important

    J. Atherosclerosis : Hopkins PN, 199717, 2792

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    Intestinal Cholesterol Absorption

    Bays H et al. Expert Opin Pharmacother 2003;4:779-790.

    Intestinal

    epithelial cell

    Biliary

    cholesterol

    Dietary

    cholesterol

    Luminal

    cholesterol

    Micellar

    cholesterol

    Bile

    acid

    Cholesteryl esters

    Freecholesterol

    excretion

    uptake

    ACAT

    ABCG5ABCG8

    (esterification)

    MTP

    CM

    Throughlymphatic

    system to

    the liver

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    Lymph Enterocyte IntestinalLumen

    Cholesterol Absorption

    Cholesterol

    NPC1L1

    CholesterylEster ABCG5/G8

    ACAT

    Ezetimibe

    Avasimibe

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    Lymph Enterocyte IntestinalLumen

    Triglyceride Absorption

    2 Fatty Acid

    +Monoglyceride

    DGAT

    Triglyceride

    www drsarma in

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    CE

    A-I

    CE

    A-I

    CE

    A-II A-II

    HDL 1 HDL 2 HDL 3

    APO A IAtheroprotective

    Alcohol increasesAthero-neutral

    The soldiers

    The soldier-like

    HDL Sub types

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    LIVER

    Reverse Cholesterol Transport

    MF in Vascular

    Endothelium

    Free Chol.

    L CAT

    Enzyme

    UECEC

    HDL

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    HDL Metabolism and

    Reverse Cholesterol Transport

    Liver

    ABC1 = ATP-binding cassette protein 1; A-I = apolipoprotein A-I;

    CE = cholesteryl ester; FC = free cholesterol;

    LCAT = lecithin:cholesterol acyltransferase;

    SR-BI = scavenger receptor class BI

    Mature HDL

    CE

    A-I

    CE

    CEFCFC

    LCATFC

    Bile

    SR-BI

    A-I

    ABC1

    MacrophageNascent

    HDL

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    B

    SRA

    Mature HDL

    Role of CETP in HDL Metabolism

    A-I

    Liver

    CE

    CEFC

    FC

    LCATFC

    Bile

    SR-BI

    A-I

    ABC1

    Macrophage

    CE

    CETP = cholesteryl ester transfer protein

    LDL = low-density lipoprotein

    LDLR = low-density lipoprotein receptor

    VLDL = very-low-density lipoprotein

    LDLR

    VLDL/LDL

    CETP

    Nascent HDL

    CE

    Torcitrapib

    X

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    Hyperlipidemias

    Secondary 95%

    Primary 5%

    Familial & genetic

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    Clinical Action

    Presence of secondary causesof Hyperlipidemia Order for full lipid profile (LP)HT also

    Presence of hyperlipidemiaincreased TG or EC

    Investigate for all secondary causes For all above 20 years once in every 5 years

    For those above 45 yrsonce 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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    Clinical Photoes

    Tuberous xanthoma.

    Flat-topped, yellow, firm tumor

    Xanthelasma. Multiple, longitudinal, creamy-

    orange, slightly elevated papules on eyelids .

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    Clinical Photoes

    Tendinous xanthomas. Large sub-cutaneous tumors adherent to the

    Achilles tendons.Papular eruptive xanthomas. Multiple,

    discrete, red-to-yellow confluent papules

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    Evaluation

    1. History of eruptive xanthomas, Abd. pain

    2. H/o wt. gain, DM, estrogens, Alcohol, Ex.

    3. Fasting Lipid profile (TC, LDL, HDL, TG)

    4. OGTT, TSH, Liver & Renal Function tests

    5. CHD assessment by ECG, TMT, Angio

    6. Risk factor assessment, Family H/o P.CHD

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    The Weapons in our hand

    Dietand Exercise (Life Style)

    Drug therapy

    1. HMGCo A Reductase Inhibitors

    2. Fibric Acid derivatives

    3. Nicotinic Acid

    4. Ezetimibe

    5. Bile Acid binding Resins (BAR)

    6. Probucol

    HMG is Hydroxy Methyl Glutaryl

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    New Treatments

    Drug therapy

    1. Colesevelam (BAR)

    2. Phytosterols

    3. AvasimibeACAT inhibitor

    4. TorcetrapibCETP inhibitor

    5. Drugs decreasing Apo B synthesis6. Selective LDL apopheresis

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    Therapeutic Lifestyle Changes - TLC

    Nutrient Recommended Intake

    Saturated fat < 7% of calories

    PUFA fat Up to 10% of calories

    MUFA fat Up to 20% of calories Total fat 2535% of calories

    Carbohydrate 5060% of calories

    Fiber 2030 grams per day Protein Approx. 15% of calories

    Cholesterol Less than 200 mg/day

    DIETARY THERAPY

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    Our dietary fats

    SFA (saturated)meet and diary products,

    coconut oil, Kernel, Ghee, Butter, Palm oil,

    Trans fatty acids in vanaspati, chocolates

    confectionaries, baked, deep fat fried food

    MUFA (N1)Olive oil, Gingili oil

    PUFA (N6)Soya, Sun Flower oil, GN oil

    PUFA (N3)Fish oilsTwice a wk 76% CAD

    Legumes, fruits, olive oil all cause mortality

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    Treatment of LDLc

    High LDLc

    Therapeutic Lifestyle Change

    Add on drug - EZ , Niacin, BAR

    Therapy of Choice: Statin

    Drug Therapy

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    StatinsMechanism of Action

    1. Reduce hepatic cholesterol synthesis (HMG CoA),

    2. lowering intracellular cholesterol,

    3. Upregulation of LDL receptor and

    4. the uptake of non-HDL from circulation.

    LDL receptormediated

    hepatic uptake of LDL

    and VLDL remnants

    Serum VLDL remnants

    Serum LDL-C

    Cholesterol

    synthesisLDL receptor

    (BE receptor)

    synthesisIntracellular

    Cholesterol

    Apo B

    Apo E

    Apo B

    Systemic CirculationHepatocyte

    LDL

    Serum IDL

    VLDLR

    VLDL

    HMGCoA

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    Time course of Statin effects

    * Time course establishedDays Years

    LDL-Clowered*

    Inflammationreduced

    Vulnerable

    plaquesstabilized

    Endothelial

    functionrestored

    Ischemic

    episodesreduced

    Cardiac events

    reduced*

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    HMG C A R d

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    HMG CoA Reductase

    Inhibitors (Statins)

    Statin Dose Range

    Lovastatin 2080 mg

    Pravastatin 2040 mg

    Fluvastatin 2080 mg

    Simvastatin 2080 mg

    Atorvastatin 1080 mg

    Rosuvastatin 520 mg

    Cerivastatin 0.40.8 mg

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    Atorvastatin211 mg/dl*

    Simvastatin

    219 mg/dl*

    -60%

    -50%

    -40%

    -30%

    -20%

    -10%

    0%

    LDL-C Lowering - Statin Dose

    Adapted from Jones P et al.Am J Cardiol1998;81:582-587.

    Daily Dose

    10 mg

    20 mg

    40 mg

    80 mg16% with

    3 Titrations

    13%

    38%

    46%

    51%

    54%

    28%

    35%

    41%

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    HMG CoA Reductase Inhibitors (Statins)

    Common side effects

    Headache, Myalgia, Fatigue, GI intol. Flu-like symptoms

    Increase in liver enzymesserious problems are very rare

    Occurs in 0.5 to 2.5% of cases in dose-dependent manner

    Myopathy occurs in 0.2 to 0.4% of patients Rare cases of Rhabdomyolysis

    We can reduce this risk by

    Cautiously using statins in impaired renal function

    Using the lowest effective dose

    Cautiously combining statins with fibrates

    Muscle toxicity requires the discontinuation of statin

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    Short falls of Statins

    Effectiveness and community impact are to be improved

    Rebound increase in lipids and of events after

    withdrawal of statin Rx.

    High rate of discontinuation by patients

    Differences in the efficacy of different statins

    They reduce only endogenous lipidsIndividual variation

    Modest effect on TG and HDL, No effect on Lp(a)

    No effect on chylomicrons; escape phenomenon

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    Lymph Enterocyte IntestinalLumen

    Ezetimibe

    Cholesterol

    NPC1L1

    CholesterylEster ABCG5/G8

    ACAT

    Ezetimibe

    X

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    Dual Inhibition

    Duodenum

    Jejunum

    Ileum

    CM

    apoB48

    Liver

    CMRemnantapoB48

    VLDLapoB100

    EzetimibeX

    LDLapoB100

    XStatin

    Colon

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    Ezetimibe Efficacy (10 + 10 = 80)

    Ballantyne CM et al. Circulation 2003;107:2409-2415.

    Atorvastatin

    40 mg

    (n=66)

    20 mg

    (n=60)

    10 mg

    (n=60)

    53%

    37%42%

    45%

    54%

    P < 0.01

    80 mg

    (n=62)

    -60%

    -50%

    -40%

    -30%

    -20%

    -10%

    0%

    Ezt + Ator

    10+10 mg(n=65)

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    Bile Acid Resins: Mechanism of Action

    Net Effect - LDL-C

    Gall Bladder

    LDL Receptors

    VLDL and LDL removal

    Cholesterol 7- hydroxylaseConversion of cholesterol to BA

    BA Secretion

    Liver

    BA Excretion

    Terminal Ileum

    Bile Acid

    Enterohepatic Recirculation

    Reabsorption of

    bile acids

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    Bile Acid Resins (BAR)

    Major actions Reduce LDLc by 1530%

    Raise HDLc by 35%

    May increase TG

    Side effects GI distress / constipation / nausea

    Decreased absorption of other drugs

    Contra indications

    Dysbetalipoproteinemia,

    Biliary Obstruction

    Raised TG (especially >400 mg/dL)

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    Bile Acid Resins

    Drug Dose Range

    Cholestyramine 416 g

    Colestipol 520 g

    Colesevelam 2.63.8 g

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    T f HDL

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    Treatment of HDLc

    Low HDLc

    Therapeutic Lifestyle Change

    Add on drug - Finofibrate

    Therapy of Choice : Niacin

    Drug Therapy

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    C f L HDL

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    Causes of Low HDLSmoking

    Obesity (visceral fat), Physical inactivity

    Very high Carbohydrate diet

    Type II Diabetes

    Hyper-triglyceridemia

    Drugs like beta-blockers, androgenic steroids

    and androgenic progestins

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    Nicotinic AcidMechanism of Action

    Liver CirculationHDL

    Serum VLDL

    results in reduced

    lipolysis to LDL

    Serum LDL

    VLDL

    Decreases hepatic production of VLDL and of apo B

    VLDLsecretion

    Apo B

    Hepatocyte Systemic Circulation

    Mobilization of FFA

    TG

    synthesis

    VLDL

    LDL

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    Eff f Ni i Li i

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    Effect of Niacin on Lipoproteins

    Adapted from Knopp RH. N Engl J Med 1999;341:498-511..

    0 1 g / d 2 g / d 3 g / d

    Baseline

    -15%

    12.5%

    25%

    -30%

    HDL-C with Niaspan

    TG with Niaspan

    TG with crystalline niacin

    LDL-C with Niaspan

    LDL-C with crystalline niacin

    35%HDL-C with crystalline niacin

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    Ni ti i A id

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    Nicotinic Acid Products available

    Immediate-release, 24 g/d, Sustained Release 3 g /d Extended-release (Niaspan) 12 g/d

    Best agent to raise HDL-C

    Reduces coronary events

    Adverse effects

    Flushing, itching, headache (immediate-release, Niaspan)

    Hepatotoxicity, GI (sustained-release)

    Activation of peptic ulcer

    Hyperglycemia and reduced insulin sensitivity

    Contraindications

    Active liver disease or unexplained LFT elevations

    Peptic ulcer disease

    Coronary heart disease and HDL C

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    Coronary heart disease and HDL-C

    Framingham Heart Study

    Gordon, Castelli et al. Am J Med 1977; 62: 707714

    0

    50

    100

    150

    200

    Rate/

    1000

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    Relative risks of MI

    3.21

    3.78

    1.00

    2.41Low HDL cholesterol

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    HDL-C vs LDL-C

    as a predictor of CHD risk

    *Men aged 5070 Gordon, Castelli et al. Am J Med 1977; 62: 707714

    100 mg/dl 160 mg/dl 220 mg/dl0

    0.5

    1

    1.5

    2

    2.5

    3

    Risk of CAD over 4

    years of follow-up*

    LDL-C

    85 mg/dl

    65 mg/dl

    45 mg/dl

    25 mg/dl

    CHD RR

    HDL-C

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    68

    T f TG

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    [email protected]

    Treatment of TG

    High TG

    Therapeutic Lifestyle Change

    Add on drugStatin, Niacin

    Therapy of Choice : Fibrate

    Drug Therapy

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    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

    F fib t

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    Fenofibrate

    Mode of Action Enhances the activity of lipoprotein lipase

    Reduces hepatic fatty acid synthesis

    Inhibits HMG co-enzyme A reductase activity

    Reduces the CETP activity

    Increases the LCAT activity Increases the production of Apo AI and Apo A II

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    Fibric Acid Derivatives

    Major actions

    Lower TG 2050%,VLDL synthesis

    Raise HDL-C 1020%

    LDL (TG is N), LDL (TG is ) Increase the SDL particle size (less athero)

    Side effects

    Dyspepsia, gallstones, myopathy, Abn. LFT Contraindications

    Severe renal or hepatic / biliary disease

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    Fibric Acid Derivatives

    Drug Dose

    Clofibrate 1000 mg BID

    Bezafibrate 200 mg BIDGemfibrozil 600 mg BID

    Fenofibrate 200 mg OD

    Fenofibrate micronized 160 mg OD

    73

    T t t f LDL + TG

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    [email protected]

    Treatment of LDL + TG

    Combined

    Therapeutic Lifestyle Change

    Add on drugNiacin, BAR

    Therapy of Choice : Statin + Fibrate

    Drug Therapy

    74

    Statin + Fibrate

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    [email protected]

    Da Col PG et al. Curr Ther Res Clin Exp 1973;53:473-482.

    Statin + Fibrate

    -60

    -50

    -40

    -30

    -20

    -10

    0

    10

    20

    30

    Simva +

    Gemfibrozil

    50%

    39%

    16%22%

    41%

    28%

    Ator or Simva +

    Fenofibrate

    230 332

    38

    191166

    LDLTG

    HDL

    LDL

    TG

    HDL

    PercentChange

    34

    75

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    Statin + FibratePrecautions

    Use statin alone for non-HDL-C goals

    Use fish oils or niacin rather than fibrates

    Keep the doses of the statin and fibrate low

    Dose the fibrate in the AM and the statin in the PM

    Avoid (or cautiously use) combo in renal impairment

    Teach the patient to recognize muscle symptoms

    Discontinue therapy if muscle symptoms are present

    and CK is >10 times the upper limit of normal

    76

    b l

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    Probucol

    1. Probucol (Lorelco) 500mg b.i.d with food

    2. Third line drugerratic effect on LDL & HDL

    3. Lowers Cholesterol and the only drug which

    regresses xanthomas

    4. It is an antioxidant of LDL

    5. Diarrohea, flatulence, nausea, increases QTc

    6. Can be combined with BAR

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    The Three Canons

    LDL - STATIN

    DYSLIPIDEMIA

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    How do we treat ?

    Increased LDL Statins +/- EZ

    Increased TG Fibrates

    Decreased HDL Niacin

    Increased Lp(a) Niacin

    Increased LDL + TG Statin + Fibrate

    LDL + HDL Statin + Niacin TG + HDL Fibrate + Niacin

    79

    Summary of Drug choice

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    Summary of Drug choice

    Lipid abnormality type First choice Additional Remarks

    LDL Statin Ezetimibe Myopathy

    TG Fibrate Niacin CHO intake

    HDL Niacin Fibrate Exercise

    LDL + TG Statin + Fibrate Niacin Myo risk

    LDL + HDL Statin + Niacin Fibrate Exercise

    TG + HDL Fibrate + Niacin Statin Exercise

    LDL + TG + HDL Statin + Fibrate E, N, BA, FO Myo risk

    Atherogenecity of small dense LDL

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    Atherogenecity of small, dense LDL

    SDL is highly atherogenic. It

    Generates free radicals

    Increases trans endothelial filtration

    Increases susceptibility to oxidation

    Reduces affinity for the LDL receptor

    Increased binding to intimal proteoglycan

    Formation of pro-aggregators / vasoconstrictors

    Impaired in vivo ED independent of HDL, LDL, TG

    Circulation, 2000, 102: 716-721

    81

    L ( ) Li l

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    Lp(a) or Littlea

    Similar to LDL molecule

    Apo B + additional Apo a attached by S=S bond

    Primary determinant is genetic

    Normal value 20 mg%, > 30 high risk

    It competes with plasminogen because of its

    structural similarity and so interferes with

    plasmin synthesis and thrombolytic pathway

    Nicotinic acid, ? Bezafibrate, Estrogens it

    Phenotype B or ALP

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    This ALP or phenotype B is present andseen in most often

    Insulin resistant individuals

    Diabetics Obese persons

    Sedentary life style

    More prevalent in India

    Apo A I Apo B will be < 1

    Phenotype B or ALP

    Cumulative Distribution of TG Levels

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    0

    10

    20

    30

    40

    50

    60

    70

    80

    90

    100

    20 40 60 80 100120 140160180200 220240 260280 300 500

    Phenotype A

    Phenotype B

    % Cumulative

    frequency

    TG (mg/dL)

    Phenotypes A and B

    Austin M et al. Circulation. 1990;82:495-506.

    Cumulative Distribution of HDL levels

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    20 25 30 35 40 45 50 55 60 65 70 75 80

    Phenotype A

    Phenotype B

    % Cumulativefrequency

    HDL-C (mg/dL)

    10090

    80

    70

    60

    50

    40

    30

    20

    Phenotypes A and B

    Austin M et al. Circulation. 1990;82:495-506.

    85

    H t i

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    Homocysteine

    Normal value is up to 10 mols./L

    Folic acid, Vitamin B6and B12are essential for

    the normal transulfuration and remethylation

    cycles Excess of homocystine generates oxidative

    stress on the cell membranes. DNA and protein

    denaturation through ROS formation Folic acid 5 mg/ day+ Vit. B6and B12are to be

    given on regular basis

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    Summary of Drug choice

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    Summary of Drug choice

    Lipid abnormality type Advised Rx. Remarks

    Homocysteine Folic acid B6+ B12helps

    Small dense LDL Statin + Fibrate Aggressive Rx.

    Little a or LP(a) Niacin Statin no effect

    Phenotype B Under research DM, Obesity

    in Phenotype A Under research Aerobic exercise

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    88

    Ath l i d IR d DM

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    Atherosclerosis and IR and DM

    Hypertension

    Obesity

    Hyperinsulinemia

    Diabetes

    Hypertriglyceridemia

    Small, dense LDL

    Low HDL

    Hypercoagulability

    Insulin

    ResistanceAtherosclerosis

    89

    D li id i i IR d DM

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    Elevated TG

    Elevated VLDL

    Reduced HDL-C Increase in SD-LDL

    Decrease in Apo A I

    Increase in Apo B

    Ratio of Apo B / Apo 1 > 2

    Dyslipidemia in IR and DM

    All Diabetics must be given STATIN

    90

    Diabetes Treatment and Lipids

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    Diabetes Treatment and Lipids

    Type Rx used Effect on lipids

    1. Insulin Favourable

    2. Metformin Mildly favourable

    3. Sulfonylureas Not favourable

    4. Glitazones Favourable

    5. Acarbose No effect

    91

    Hypertension Treatment and Lipids

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    [email protected]

    Hypertension Treatment and Lipids

    Type Rx used Effect on lipids

    1. Diuretics Unfavourable

    2. Indapamide Mildly favourable

    3. ACEi and ARB Very favourable

    4. Betablockers Unfavourable

    5. Ca channel blockers No effect

    92

    W b R Li id

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    [email protected]

    Web Resources on Lipids

    www.lipidsonline.org

    www.hypertensiononline.org

    www.ncbi.nlm.nih.gov

    www.univbaylore.org

    93

    http://www.lipidsonline.org/http://www.hypertensiononline.org/http://www.ncbi.nlm.nih.gov/http://www.univbaylore.org/http://www.univbaylore.org/http://www.ncbi.nlm.nih.gov/http://www.hypertensiononline.org/http://www.lipidsonline.org/
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    Announcements

    1.Purpose, Men behind

    2.Our emphasis and topics

    3.Frequency, timings4.Very informal - Interactive

    5.Funds, sponsors, venues

    6.Let us know you correctly

    7.Feed back, make friends

    94

    CD ROM A il bl

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    CD ROM Available

    The contents of my todays presentations

    are made available in a CD-ROM format

    This CD, in addition, contains my talks on

    Asthma, COPD, Hypertension, ECG, CAD

    Dyslipidemias, Diabetes, Osteoporosis

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    www.drsarma.in

    Visit us at: www.drsarma.in

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    It is time for

    http://www.drsarma.in/http://www.drsarma.in/
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    It is time for

    Coffee Break