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Welcome to You All. Dyslipidemias Dx. and Rx. Dr.Sarma RVS N, M.D., M.Sc (Canada) Consultant in Medicine and Chest, President IMA – Tiruvallur Branch # 3, Jayanagar, Tiruvallur – 602 001 +91 98940 60593, (411 6) 260593. CD ROM Available. The contents of today’s presentation

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Welcome to You All

Dr.Sarma@works


Dyslipidemias Dx. and Rx.

Dr.Sarma RVSN, M.D., M.Sc (Canada)

Consultant in Medicine and Chest,

President IMA – Tiruvallur Branch

# 3, Jayanagar, Tiruvallur – 602 001

+91 98940 60593, (4116) 260593

Dr.Sarma@works


CD ROM Available

The contents of today’s presentation

are available in a CD-ROM format

for computer and VCD player use.

This CD, in addition, contains our talks on

ECG, Asthma, COPD, Hypertension Rx. also

Dr.Sarma@works


Adult Treatment Panel III (ATP III) Guidelines -2002Updated October 2004

National Cholesterol

Education Program - NCEP

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Guidelines that aren’t implemented never work

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CHD Risk Factors ranking - PROCAM Study

Smoking2.30.001

LDL cholesterol (mg%)

> 100 but < 1601.90.01

> 1604.30.001

Hypertension (SBP > 140; DBP > 90)1.80.001

HDL cholesterol (mg%)

40 to 551.70.01

< 402.70.001

Triglycerides (mg%)

105- 1671.60.01

>1672.60.001

Fasting blood glucose (mg%)

110 - 1261.40.05

> 1261.90.01

Family history of MI1.40.05

Risk factor Relative risk P Value


Emerging Risk Factors

  • Lipoprotein (a)

  • Homocysteine

  • Prothrombotic factors

  • Pro-inflammatory factors

  • Metabolic syndrome

  • Sub-clinical atherosclerosis

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CHD Risk Equivalents

  • Diabetes Mellitus

  • Peripheral Vascular Disease

  • > 20% in Framingham risk score

  • Carotid atheroma

  • Reno-vascular Disease

    All forms of AVD

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AVD – Clinical Manifestations

For every thing the common denominator is ED

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Progression of Atherosclerosis

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Lipid Peroxidation

LDL, IDL

Not normally taken up by the vessel wall

ROS – Free radicals and Pro-oxidants

Freely enters the vessel wall

Oxidized LDL, IDL

Macrophages

Endothelium

Scavenger pathway

Foam Cells

Cytokines, GF

Atherosclerosis

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The Havoc by LDL at the endothelium

Vessel Lumen

Monocyte

LDL

AdhesionMolecules

Endothelium

MCP-1

LDL

Intima

Modified LDL

Cytokines

Growth FactorsMetalloproteinases

Cell ProliferationMatrix Degradation

Macrophage

Foam Cell

Ross R. N Engl J Med 1999;340:115-126.


Vulnerable Atherosclerotic Plaque

Non-Vulnerable Atherosclerotic Plaque

Pathogenesis of ACS


Plaque Rupture with Thrombus


TG

EC

Apoprotein boat

Lipid Transport

Apo A I and A II for HDLApo B100 for LDL, Lp(a)

Apo B100+C+E – VLDL, IDLApo B48+C+A+E – Chy. microns

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HDL

A I, A II

B 100

TG

TG

C

TG

TG

C

C

B 48+E+C

CM

B 100 + E +C

Lipoproteins

LDL

VLDL

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Cholesterols and Apoproteins

  • Total Cholesterol< 200Apoprotein

  • ‘Bad’ CholesterolsApo B type

    • LDLc, IDLc< 100B100 or B100 +E

    • VLDLc, VLDLr< 30B100 + E + C

    • Lp(a), small LDL< 20B100 + (a)

  • ‘Good’ CholesterolsApo A type

    • HDL 1, HDL 2, HDL 3> 50A I and A II

HDL 1 and HDL 2 are protective

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Chylomicrons

<< 1.006

VLDL

< 1.006

IDL

< 1.019

LDL

Small LDL

HDL

< 1.063

< 1.085

< 1.210

Particle size & Density

Atherogenicity increases as density increases

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Atherogenic Particles

Apolipoprotein B

Measurements

Non-HDL-C

VLDL

VLDLR

IDL

LDL

SDL

TG-rich lipoproteins

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Two Types of Lipids

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Lipid Profile Report

PP

Fasting

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Lipid Calculations

200

  • Total Cholesterol

    HDL Cholesterol

    LDL Cholesterol (TC –(HDL+VLDL))

    VLDL Cholesterol (1/5 of TG)

    B.Triglycerides

50

120

30

150

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The Good and Bad

  • Total Cholesterol < 200

  • ‘Good’ Cholesterols

    • HDL 1, HDL 2, HDL 3 > 50

  • ‘Bad’ Cholesterols (Non HDLc)< 150

    • LDLc, IDLc < 100

    • VLDLc, VLDLr < 30

    • Lp(a), small LDL< 20

HDL 1 and HDL 2 are protective

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How it should be reported ?

InterpretationHDL – N,LDL – High , TG - HIGH

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Today’s Safer Values

  • Total Cholesterol < 200

  • Triglycerides < 150

  • LDL Cholesterol < 100

  • HDL Cholesterol > 50 (for women 55)

  • Bad Cholesterols the lower the better

  • Good Cholesterols the higher the better

  • Non HDL Cholesterol < 130

  • Lp(a) values < 20

  • Homocysteine < 14 μ mols per liter

Dr.Sarma@works


Indian Specialty

A. Isolated low LDL32.90%

B. Isolated low HDL21.35%

C. Isolated high TG10.45%

↑TG

↑LDL

The Triad

↓HDL

IHJ, 2000, 52: 173-177

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

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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 lipids are one aspects

  • Tissue lipid content is more important

    J. Atherosclerosis : Hopkins PN, 1997 – 17, 2792

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Relative risk of CHD

1.6

6

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CM

MTP

ACAT

Intestinal Cholesterol Absorption

Biliarycholesterol

Dietarycholesterol

Intestinal epithelial cell

Through lymphatic system to the liver

Luminalcholesterol

Cholesteryl esters

Bile acid

excretion

(esterification)

ABCG5ABCG8

Micellarcholesterol

Freecholesterol

uptake

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

Dr.Sarma@works


Cholesterol Absorption

Lymph

Enterocyte

IntestinalLumen

Ezetimibe

Cholesterol

NPC1L1

ACAT

CholesterylEster

ABCG5/G8

Avasimibe

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Liver

Duodenum

BiliaryTransportand Storage

Jejunum

Ileum

Colon

Fat Absorption

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Triglyceride Absorption

Lymph

Enterocyte

IntestinalLumen

2 Fatty Acid

+

Monoglyceride

DGAT

Triglyceride

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Chylomicron Formation

Lymph

Enterocyte

IntestinalLumen

CM

apoB48

Triglyceride

CholesterylEster

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Structure of HDL Particle

A-I

A-I

CE

TG

A-II

A-I, A-II = apolipoprotein A-I, A-II; CE = cholesterol ester; TG = triglycerides

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A-I

CE

HDL Types

A-I

CE

CE

A-II

A-II

HDL 1

HDL 2

HDL 3

APO A I Protective

Alcohol increases

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MF in Vascular Endothelium

LIVER

EC

Free Chol.

HDL

Reverse Cholesterol Transport

UEC

L CAT Enzyme

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A-I

CE

HDL Metabolism and Reverse Cholesterol Transport

Bile

A-I

FC

CE

CE

LCAT

FC

FC

ABC1

Nascent HDL

SR-BI

Macrophage

Liver

Mature HDL

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

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Role of CETP in HDL Metabolism

Bile

Macrophage

Nascent HDL

Mature HDL

A-I

A-I

FC

CE

CE

LCAT

FC

CE

ABC1

FC

SR-BI

SRA

CETP

X

Liver

LDLR

Oxidation

CE

B

VLDL/LDL

CETP = cholesteryl ester transfer proteinLDL = low-density lipoprotein LDLR = low-density lipoprotein receptorVLDL = very-low-density lipoprotein

Torcitrapib

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Hyperlipidemias

Primary 5%

Familial & genetic

Secondary 95%

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Secondary Hyperlipidemia

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Clinical Action

  • Presence of secondary causes of Hyperlipidemia

    • Order for full lipid profile (LP) – HT also

  • Presence of hyperlipidemia – increased TG or EC

    • Investigate for all secondary causes

  • 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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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

  • History of eruptive xanthomas, Abd. pain

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

  • Fasting Lipid profile (TC, LDL, HDL, TG)

  • OGTT, TSH, Liver & Renal Function tests

  • CHD assessment by ECG, TMT, Angio

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

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Treatment Strategy

Lipid Profile, Risk Assessment

LDL > 100

Look For Sec. Causes

Treat the cause, if found

Treatment

NO CHD

CHD +

Primary Prevention

Sec. Prevention

LDL < 130

2 or more RF

< 2 RF

Low Risk

High Risk

LDL > 100

LDL <160

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Treatment Plan - LDLc

For Indians all the values must be 20 mg less

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Treatment Options

  • Diet – Two step approach

  • Drug therapy

    • HMG¢co A Reductase Inhibitors

    • Fibric Acid derivatives

    • Nicotinic Acid

    • Ezetimibe

    • Bile Acid binding Resins (BAR)

    • Probucol

¢HMG is Hydroxy Methyl Glutaryl

Dr.Sarma@works


New Treatments

Drug therapy

  • Colesevelam (BAR)

  • Phytosterols

  • Avasimibe – ACAT inhibitor

  • Torcetrapib – CETP inhibitor

  • Drugs decreasing Apo B synthesis

Dr.Sarma@works


Therapeutic Lifestyle Changes - TLC

NutrientRecommended Intake

  • Saturated fat< 7% of calories

  • PUFA fatUp to 10% of calories

  • MUFA fat Up to 20% of calories

  • Total fat25–35% of calories

  • Carbohydrate50–60% of calories

  • Fiber20–30 grams per day

  • ProteinApprox. 15% of calories

  • CholesterolLess than 200 mg/day

DIETARY THERAPY

Dr.Sarma@works


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 oils – Twice a wk ↓ 76% CAD

  • Legumes, fruits, olive oil – ↓ all cause mortality

Dr.Sarma@works


Treatment of ↑LDLc

High LDLc

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice: Statin

Add on drug - EZ , Niacin, BAR

Dr.Sarma@works


VLDL

Cholesterol synthesis

Apo B

LDL receptor

(B–E receptor)

synthesis

VLDLR

LDL receptor–mediated hepatic uptake of LDL and VLDL remnants

Apo E

Serum LDL-C

Intracellular Cholesterol

Apo B

LDL

Serum VLDL remnants

Serum IDL

Hepatocyte

Systemic Circulation

Statins – Mechanism of Action

HMGCoA

  • Reduce hepatic cholesterol synthesis (HMG CoA),

  • lowering intracellular cholesterol,

  • Upregulation of LDL receptor and

  • ↑ the uptake of non-HDL from circulation.

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CHD Risk Reduction – Statin Therapy

Relative Risk Reduction (%)

+20

0

–5

–10

–15

–20

–25

–30

–35

–40

–45

–50

Endpoints

Major coronary events

Coronary deaths

Cardiovascular deaths

Noncardiovascular events

Total mortality

Strokes

Intermittent claudication

Angina

La Rosa JC et al. JAMA 1999;282:2340-2346.

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Time course of Statin effects

Vulnerableplaquesstabilized

LDL-C lowered*

Inflammationreduced

Endothelialfunctionrestored

Ischemicepisodesreduced

Cardiac eventsreduced*

Days

Years

* Time course established

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HMG CoA Reductase Inhibitors (Statins)

Statin Dose Range

Lovastatin 20–80 mg

Pravastatin 20–40 mg

Fluvastatin 20–80 mg

Simvastatin 20–80 mg

Atorvastatin 10–80 mg

Rosuvastatin 5–20 mg

Cerivastatin 0.4–0.8 mg

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10 mg

20 mg

40 mg

80 mg

LDL-C Lowering - Statin Dose

Atorvastatin211 mg/dl*

Simvastatin219 mg/dl*

Daily Dose

Mean % Change from Baseline

28%

38%

35%

13%

41%

46%

16% with3 Titrations

51%

54%

Adapted from Jones P et al. Am J Cardiol 1998;81:582-587.

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HMG CoA Reductase Inhibitors (Statins)

  • Common side effects

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

  • Increase in liver enzymes – serious 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 lipids – Individual variation

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

  • No effect on chylomicrons; escape phenomenon

Dr.Sarma@works


Ezetimibe

Lymph

Enterocyte

IntestinalLumen

Ezetimibe

Cholesterol

X

NPC1L1

ACAT

CholesterylEster

ABCG5/G8

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X

Ezetimibe

Dual Inhibition

LDLapoB100

Liver

Statin

Duodenum

X

VLDLapoB100

Jejunum

Ileum

CM RemnantapoB48

CM

apoB48

Colon

Dr.Sarma@works


Atorvastatin

Ezt + Ator

10+10 mg

(n=65)

Mean % Change in LDL-C from Baseline

10 mg(n=60)

20 mg(n=60)

40 mg(n=66)

80 mg(n=62)

–37%

–42%

–45%

–53%

–54%

P < 0.01

Ezetimibe Efficacy (“10 + 10 = 80”)

Dr.Sarma@works

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


  •  Cholesterol 7- hydroxylase

  • Conversion of cholesterol to BA

  • BA Secretion

Gall Bladder

Bile Acid

Enterohepatic Recirculation

Liver

Terminal Ileum

  • LDL Receptors

  • VLDL and LDL removal

Reabsorption of bile acids

  • BA Excretion

Net Effect -  LDL-C

Bile Acid Resins: Mechanism of Action

Dr.Sarma@works


Bile Acid Resins (BAR)

Major actions

  • Reduce LDLc by 15–30%

  • Raise HDLc by 3–5%

  • 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)

Dr.Sarma@works


Bile Acid Resins

Drug Dose Range

Cholestyramine4–16 g

Colestipol5–20 g

Colesevelam2.6–3.8 g

Dr.Sarma@works


Treatment of ↓ HDLc

Low HDLc

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice : Niacin

Add on drug - Finofibrate

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Prevalence of coronary heart disease and its risk factors in Asian Indians

Atherosclerosis , Rosemount , IL Oct 6-11 , 1991

The CADI study [Coronary Artery Disease in Asian Indians]

14% of Asian Indian males & 5% of females have Optimal HDL

In Indian patients with CAD, High TG levels are found more often than high cholesterol levels.

Journal, Ind. Acad. clin. med vol 2 Jul-Sept 2001


Causes of Low HDL

  • Smoking

  • Obesity (visceral fat), Physical inactivity

  • Very high Carbohydrate diet

  • Type II Diabetes

  • Hyper-triglyceridemia

  • Drugs like beta-blockers, androgenic steroids

    and androgenic progestins

Dr.Sarma@works


LDL

Nicotinic Acid – Mechanism of Action

Mobilization of FFA

Apo B

Serum VLDL results in reduced lipolysis to LDL

VLDL

VLDL

TG synthesis

VLDL secretion

Serum LDL

HDL

Liver

Circulation

Hepatocyte

Systemic Circulation

Decreases hepatic production of VLDL and of apo B

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35%

HDL-C with crystalline niacin

25%

HDL-C with Niaspan®

12.5%

Baseline

LDL-C with Niaspan®

LDL-C with crystalline niacin

-15%

TG with Niaspan®

-30%

TG with crystalline niacin

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

Effect of Niacin on Lipoproteins

Dr.Sarma@works

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


Nicotinic Acid

  • Products available

    • Immediate-release, 2–4 g/d, Sustained Release 3 g /d

    • Extended-release (Niaspan®) 1–2 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

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Coronary heart disease and HDL-CFramingham Heart Study

200

150

Rate/1000

100

Women

50

Men

0

<25

25–34

35–44

45–54

55–64

65–74

75+

HDL-C (mg/dl)

Gordon, Castelli et al. Am J Med 1977; 62: 707–714


Relative risks of MI

The Physicians Health Study

3.78

3.21

Low HDL cholesterol

<47 mg/dl

2.41

1.00

High HDL cholesterol

47 mg/dl

Low total cholesterol

<212 mg/dl

High total cholesterol

212 mg/dl

Stampfer, Sacks et al. N Engl J Med 1991; 325: 373–381


HDL-C vs LDL-C as a predictor of CHD risk

CHD RR

Risk of CAD over 4

years of follow-up*

3

2.5

HDL-C

2

1.5

25 mg/dl

45 mg/dl

1

65 mg/dl

0.5

85 mg/dl

0

100 mg/dl

160 mg/dl

220 mg/dl

LDL-C

*Men aged 50–70

Gordon, Castelli et al. Am J Med 1977; 62: 707–714


Management of Low HDLc

  • LDL cholesterol is primary target of therapy

  • Weight reduction and increased physical activity (if the metabolic syndrome is present)

  • Non-HDL cholesterol is secondary target of therapy (if triglycerides 200 mg/dL)

  • Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents)

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Treatment of ↑TG

High TG

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice : Fibrate

Add on drug – Statin, Niacin

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Treatment Strategy

Fasting TG Level

TG < 150

Normal

↑Fasting TG Level

< 2 RF

Diet Modify

TG >150, No CHD

2 or > RF

Diet + Fibrate

TG > 150, CHD +

Diet + Fibrate + Niacin

TG > 500, CHD +/-

Diet + Fibrate + Statin

Dr.Sarma@works


Triglycerides

NCEP 2002 Guidelines by expert panel on TG

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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


Fibric Acid Derivatives

  • Major actions

    • Lower TG 20–50%,↓VLDL synthesis

    • Raise HDL-C 10–20%

    • ↓ 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

Dr.Sarma@works


Fibric Acid Derivatives

DrugDose

Clofibrate1000 mg BID

Bezafibrate 200 mg BID

Gemfibrozil 600 mg BID

Fenofibrate 200 mg OD

Fenofibrate micronized 160 mg OD

Dr.Sarma@works


Treatment of ↑ LDL + ↑TG

Combined

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice : Statin + Fibrate

Add on drug – Niacin, BAR

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Statin + Fibrate

Simva +Gemfibrozil

Ator or Simva +Fenofibrate

22%

16%

HDL

HDL

230

332

166

191

38

34

Percent Change

LDL

LDL

TG

TG

–28%

–39%

–41%

–50%

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

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Statin + Fibrate – Precautions

  • 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

Dr.Sarma@works


Probucol

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

  • Third line drug – erratic effect on LDL & HDL

  • Lowers Cholesterol and the only drug which regresses xanthomas

  • It is an antioxidant of LDL

  • Diarrohea, flatulence, nausea, increases QTc

  • Can be combined with BAR

Dr.Sarma@works


↓ HDL - NIACIN

↑ TG - FIBRATE

↑ LDL - STATIN

The Three Canons

DYSLIPIDEMIA

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Summary of Drug choice

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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


Lp(a) or Little‘a’

  • 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

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Phenotype B or ALP

  • This ALP or phenotype B is present and seen in most often

    • Insulin resistant individuals

    • Diabetics

    • Obese persons

    • Sedentary life style

  • More prevalent in India

  • Apo A I ÷ Apo B will be < 1


Cumulative Distribution of TG Levels Phenotypes A and B

100

90

80

70

60

% Cumulativefrequency

50

40

Phenotype A

30

Phenotype B

20

10

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

500

TG (mg/dL)

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


Cumulative Distribution of HDL levels Phenotypes A and B

100

90

80

70

60

% Cumulativefrequency

50

Phenotype A

40

Phenotype B

30

20

20

25

30

35

40

45

50

55

60

65

70

75

80

HDL-C (mg/dL)

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


Metabolic Syndrome - Characteristics


The interaction between our current genotype and our present day life style and eating habits places us at very high risk of having this phenotype B that makes us highly susceptible to Atherosclerosis.

Journal of Internal Medicine 2003:254(2):114-25


ATP-III Criteria for Metabolic Syndrome

  • Abdominal obesity (waist circumference): men >100 cm (40 in); women >88 cm (35 in)

  • Triglycerides > 150 mg/dl

  • HDL cholesterol: men < 40 mg/dl; women < 50 mg/dl

  • Blood pressure > 130/ 85 mmHg.

  • Fasting glucose > 110 mg/dl

Diagnosis of metabolic syndrome is made when 3 or more of the risk determinants shown above are present.


Homocysteine

  • Normal value is up to 15 μmols./L

  • Folic acid, Vitamin B6 and B12 are 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. B6 and B12 are to be given on regular basis

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Summary of Drug choice

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Some Brand Names

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Atherosclerosis and IR and DM

Hypertension

Obesity

Hyperinsulinemia

Diabetes

Hypertriglyceridemia

Small, dense LDL

Low HDL

Hypercoagulability

InsulinResistance

Atherosclerosis

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Dyslipidemia in IR and DM

  • Elevated TG

  • Elevated VLDL

  • Reduced HDL-C

  • Increase in SD-LDL

  • Decrease in Apo A I

  • Increase in Apo B

  • Ratio of Apo A I / Apo B < 1

All Diabetics must be given STATIN

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Diabetes Treatment and Lipids

Type Rx usedEffect on lipids

  • InsulinFavourable

  • MetforminMildly favourable

  • SulfonylureasNot favourable

  • GlitazonesFavourable

  • AcarboseNo effect

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Hypertension Treatment and Lipids

Type Rx usedEffect on lipids

  • DiureticsUnfavourable

  • IndapamideMildly favourable

  • ACEi and ARBVery favourable

  • BetablockersUnfavourable

  • Ca channel blockersNo effect

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Who is to be blamed ??

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20000 B.C.

2004

Paleolithic sup. age

Neolithic age

19th century

21st century

Processed

foods

Hunting-gathering

subsistence

Animal fats

­

and glucides

Dietary fibre

¯

High level of

Sedentary

physical activity

life

Thrifty genotype

Susceptibility genotype

Where are we heading ? ?

Technology has changed a lot in the way we live

But, we have not altered our life style

Journal of internal medicine 2003:254(2):114-25


We have to pay the very heavy price !!

What could be prevented, we treat or leave


Web Resources on Lipids

www.lipidsonline.org

www.hypertensiononline.org

www.ncbi.nlm.nih.gov

www.univ baylor.org

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CD ROM Available

The contents of today’s presentation

are available in a CD-ROM format

for computer and VCD player use.

This CD, in addition, contains our talks on

ECG, Asthma, COPD, Hypertension Rx. also

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Wishing YOU all

A HAPPAY NEW YEAR

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