You are on page 1of 70

LIPID MANAGEMENT

Why,when and how ?


( Based on NCEP ; ATP III )
Dr Putu Moda Arsana SpPD - KEMD
Department of Internal Medicine
Brawijaya University
M a l a n g

Pokok bahasan
Apa yang dimaksud dengan lipid dan
dislipidemia ?
Mengapa dislipidemia harus diobati ?
Apakah ada bukti bahwa pengobatan
dislipidemia bermanfaat ?
Kapan pengobatan harus dimulai ?
Berapa sasaran lipid yang harus dicapai ?
Bagaimana melakukan penatalaksanaan
dislipidemia yang rasional ?

LIPID
Molekul organik yang tidak larut dalam
air
Sebagian besar terdiri dari hidro karbon
Dibagi menjadi :
Lipid sederhana : asam lemak
Lipid kompleks : Ester asam lemak
( gabungan antara asam lemak dengan
alkohol; monoacylglycerol atau
triacylglycerol )

FUNGSI LIPID
Sebagai sumber dan cadangan
energi
Membentuk tekstur tubuh
Fungsi pelindung mekanik
Bahan untuk sintesis hormon
Bahan untuk sintesis dinding sel
Bahan untuk sintesis prostaglandin
dll

SUMBER LIPID

Diet / makanan ( eksogen )


Sintesis oleh tubuh ( endogen )

TRANSPORTASI LIPID
Jalur eksogen ( mengangkut lipid yang
berasal dari diet )
Jalur endogen ( mengangkut lipid yang
berasal dari sintesis oleh hati )

Lipid diangkut oleh Lipoprotein

LIPOPROTEIN
Kompleks lipid dengan protein
Terdiri dari :
Fosfolipid
Apolipoprotein
Kholesterol bebas
Kholesterol ester
Trigliserida

LIPOPROTEIN
Untuk transportasi Lipid ( Trigliserida
dan kholesterol )
Bentuk bentuk Lipoprotein :
Chylomicrons
Very Low Density Lipoprotein ( VLDL )
Intermediate Density Lipoprotein ( IDL )
Low Density Lipoprotein ( LDL )
High Density Lipoprotein ( HDL )

Lipoprotein Classes and Inflammation

Chylomicrons,
VLDL, and
their catabolic
remnants
> 30 nm

LDL

2022 nm

Potentially proinflammatory

HDL

915 nm
Potentially antiinflammatory

Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000;


149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:19871994.

LIPOPROTEIN METABOLISM

FAT

Intestine

AI

HDL

FFA

LPL
B 48

CHYL

Remnant-R

Vessel
AI
E

LDL-R

MUSCLE
FFA LPL N
or

LPL N
or

C
B 48 Chyl.

rem.
B100
C

VLDL

IDL

LPL
C

B100

FFA, glucose, insulin resistance


FAT
C

B100
FFA
Glycerol
Apoprotein

LPL

VLDL

FFA
FFA

Vessel

MUSCLE
LPL N
or

LDL-R

IDL

E
LPL,HL
CETP

B100

LDL
Small, dense

B100
C

Oxydized/glycated LDL
Pripheral TISSUE

Apa itu dislipidemia ?

Total cholesterol
LDL cholesterol
Trigliserida
( Small dense LDL )
( Non HDL cholesterol )
HDL cholesterol

Apa akibat dari dislipidemia ?

Macrophages and Foam Cells Express Growth


Factors and Proteinases
Vessel Lumen

Monocyte

Adhesion
Molecules

Cytokines

Macrophage

LDL

MCP-1

Endothelium

LDL

Modified
LDL

Foam Cell

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

Intima
Growth Factors
Metalloproteinases
Cell Proliferation
Matrix Degradation

Apakah ada bukti bahwa lipid


berbahaya dan dapat
menyebabkan adanya penyakit
kardiovaskuler ?

Pertanyaan !!
Kapan pengobatan harus dimulai ?
Berapa sasaran cholesterol yang
harus dicapai ?
Bagaimana melakukan pengobatan
dislipidemia ?
Jenis obat apa yang sesuai ?

Langkah langkah
( NCEP ; ATP III )

Tentukan faktor resiko yang ada


Hitung 10 year risk for CHD atau risk
equivalent
Tentukan kategori resiko
Tentukan sasaran lipid yang ingin dicapai
Pilih penatalaksanaan / pengobatan yang
sesuai

Faktor resiko
Major, independent risk factors
Life - habit risk factors
Emerging risk factors

Major Risk Factors ( Exclusive of LDL


Cholesterol ) That Modify LDL Goals
Cigarette smoking
Hypertension (BP 140/90 mmHg or on
antihypertensive medication)
Low HDL cholesterol (<40 mg/dL)
Family history of premature CHD
CHD in male first degree relative <55 years
CHD in female first degree relative <65 years
Age (men 45 years; women 55 years)

HDL cholesterol 60 mg/dL counts as a negative risk factor;


its presence removes one risk factor from the total count.

Life-Habit Risk Factors


Obesity (BMI 30)
Physical inactivity
Atherogenic diet

Emerging Risk Factors

Lipoprotein (a)
Homocysteine
Prothrombotic factors
Proinflammatory factors
Impaired fasting glucose
Subclinical atherosclerosis

Hitung 10 year risk for CHD

Framinghams calculator

Framingham point scores

Age
Total cholesterol
HDL cholesterol
Smokers
Systolik blood pressure

Table Estimate of 10-year risk for Men


(Framingham Point Scores)
Points

Age, y

Points

20 34

-9

35 39

-4

40 44

Total cholesterol
mg/dL

Age
20-39 y

Age
40-49 y

Age
50-59 y

Age
60-69 y

Age
70-79 y

< 160

45 49

160 199

50 54

200 239

55 59

240 279

60 64

10

280

11

65 69

11

70 74

12

75 - 79

13

Points
Age
20-39 y

Age
40-49 y

Age
50-59 y

Age
60-69 y

Age
70-79 y

Non smoker

Smoker

Systolic BP, mm Hg
< 120
120 129

If untreated
0
0

HDL,
mg/dL

Points

If treated

60

-1

50 59

40 49

130 139

140 159

160

< 40

Point
total

10-year
risk, %

<0

-< 1

10

11

12

10

13

12

14

16

15

20

16

25

17

30

Table Estimate of 10-year risk for Women


(Framingham Point Scores)
Points

Age, y

Points

20 34

-7

35 39

-3

Total cholesterol
mg/dL

Age
20-39 y

Age
40-49 y

Age
50-59 y

Age
60-69 y

Age
70-79 y

40 44

45 49

< 160

50 54

160 199

55 59

200 239

60 64

10

240 279

11

65 69

12

280

13

10

70 74

14

75 - 79

16

Points
Age
20-39 y

Age
40-49 y

Age
50-59 y

Age
60-69 y

Age
70-79 y

Non smoker

Smoker

Systolic BP, mm Hg

If untreated

If treated

< 120

120 129

130 139

140 159

160

Point
total

10-year
risk, %

<9

-< 1

10

11

12

13

14

15

16

17

18

190

20

11

21

14

HDL,
mg/dL

Points

60

-1

22

17

50 59

23

22

40 49

24

27

25

30

< 40

Kategori resiko
CHD or risk equivalent
Diabetes mellitus
PVD
10 year risk for CHD 20 %

2 or more risk factors


0 1 risk factor

LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC)
and Drug Therapy in Different Risk Categories

Risk Category
CHD or CHD Risk
Equivalents
(10-year risk
>20%)
2+ Risk Factors
(10-year risk
20%)

01 Risk Factor

LDL Goal
(mg/dL)

<100

LDL Level at
Which to Initiate
Therapeutic
Lifestyle
Changes (TLC)
(mg/dL)

LDL Level at
Which
to Consider
Drug Therapy
(mg/dL)

100

130
(100129: drug
optional)
10-year risk 10
20%: 130

<130

130
10-year risk
<10%: 160

<160

160

190
(160189: LDLlowering drug
optional)

Pilih penatalaksanaan /
pengobatan yang sesuai

ATP III Lipid and


Lipoprotein Classification
LDL Cholesterol (mg/dL)
<100
100129
130159
160189
190

Optimal
Near optimal/above optimal
Borderline high
High
Very high

HDL Cholesterol (mg/dL)


<40
60

Low
High

Total Cholesterol (mg/dL)


<200
200239
240

Desirable
Borderline high
High

Primary Prevention
Goals of Therapy
Long-term prevention (>10 years)
Short-term prevention (10 years)

Primary Prevention With


LDL-Lowering Therapy
Public Health Approach
Reduced intakes of saturated
fat and cholesterol
Increased physical activity
Weight control

Therapeutic Lifestyle Changes in


LDL-Lowering Therapy
Major Features
TLC Diet

Reduced intake of cholesterol-raising nutrients


(same as previous Step II Diet)
Saturated fats <7% of total calories
Dietary cholesterol <200 mg per day

LDL-lowering therapeutic options

Plant stanols/sterols (2 g per day)


Viscous (soluble) fiber (1025 g per day)

Weight reduction
Increased physical activity

Therapeutic Lifestyle Changes


Nutrient Composition of TLC Diet
Nutrient
Saturated fat
Polyunsaturated fat
Monounsaturated fat
Total fat
Carbohydrate
Fiber
Protein
Cholesterol
Total calories (energy)
expenditure

Recommended Intake
Less than 7% of total calories
Up to 10% of total calories
Up to 20% of total calories
2535% of total calories
5060% of total calories
2030 grams per day
Approximately 15% of total calories
Less than 200 mg/day
Balance energy intake and
to maintain desirable body weight/
prevent weight gain

A Model of Steps in
Therapeutic Lifestyle Changes
(TLC)
Visit I

6 wks

Begin Lifestyle
Therapies

Emphasize
reduction in
saturated fat &
cholesterol
Encourage
moderate physical
activity
Consider referral to
a dietitian

Visit 2
Evaluate LDL
response
If LDL goal not
achieved, intensify
LDL-Lowering Tx

Reinforce reduction
in saturated fat and
cholesterol
Consider adding
plant stanols/sterols
Increase fiber intake
Consider referral to
a dietitian

6 wks

Visit 3
Evaluate LDL
response
If LDL goal not
achieved, consider
adding drug Tx

Initiate Tx for
Metabolic
Syndrome
Intensify weight
management &
physical activity
Consider referral
to a dietitian

Q 4-6 mo

Visit N
Monitor
Adherence
to TLC

Terapi farmakologi

Drug Therapy
HMG CoA Reductase Inhibitors (Statins)
Reduce LDL-C 1855% & TG 730%
Raise HDL-C 515%
Major side effects
Myopathy
Increased liver enzymes

Contraindications

Absolute: liver disease


Relative: use with certain drugs

HMG CoA Reductase


Inhibitors (Statins)
Statin
Lovastatin
Pravastatin
Simvastatin
Fluvastatin
Atorvastatin
Cerivastatin

Dose Range
2080 mg
2040 mg
2080 mg
2080 mg
1080 mg
0.40.8 mg

HMG CoA Reductase


Inhibitors (Statins) (continued)
Demonstrated Therapeutic Benefits
Reduce major coronary events
Reduce CHD mortality
Reduce coronary procedures
(PTCA/CABG)
Reduce stroke
Reduce total mortality

Drug Therapy
Bile Acid Sequestrants
Major actions
Reduce LDL-C 1530%
Raise HDL-C 35%
May increase TG
Side effects
GI distress/constipation
Decreased absorption of other drugs
Contraindications
Dysbetalipoproteinemia
Raised TG (especially >400 mg/dL)

Bile Acid Sequestrants


Drug
Cholestyramine
Colestipol
Colesevelam

Dose Range
416 g
520 g
2.63.8 g

Demonstrated Therapeutic Benefits


Reduce major coronary events
Reduce CHD mortality

Nicotinic Acid
Major actions
Lowers LDL-C 525%
Lowers TG 2050%
Raises HDL-C 1535%

Side effects: flushing, hyperglycemia,


hyperuricemia, upper GI distress,
hepatotoxicity
Contraindications: liver disease,
severe gout, peptic ulcer

Nicotinic Acid
Drug Form
Immediate release
(crystalline)
Extended release
Sustained release

Dose Range
1.53 g
12 g
12 g

Demonstrated Therapeutic Benefits


Reduces major coronary events
Possible reduction in total mortality

Fibric Acids
Major actions
Lower LDL-C 520% (with normal TG)
May raise LDL-C (with high TG)
Lower TG 2050%
Raise HDL-C 1020%
Side effects: dyspepsia, gallstones, myopathy
Contraindications: Severe renal or hepatic disease

Fibric Acids
Drug
Gemfibrozil
Fenofibrate
Clofibrate

Dose
600 mg BID
200 mg QD
1000 mg BID

Demonstrated Therapeutic Benefits


Reduce progression of coronary lesions
Reduce major coronary events

Bagaimana melakukan
tahapan pengobatan
farmakologi ?

Progression of Drug Therapy


in Primary Prevention
Initiate
LDL-lowering
drug therapy

Start statin or
bile acid
sequestrant or
nicotinic acid

If LDL goal not


achieved,
6 wks intensify
LDL-lowering
therapy

Consider higher
dose of statin or
add a bile acid
sequestrant or
nicotinic acid

6 wks

If LDL goal not


achieved,
intensify drug
therapy or refer
to a lipid
specialist

If LDL goal
achieved, treat
other lipid risk
factors

Q 4-6 mo

Monitor
response
and
adherence
to therapy

Secondary Prevention: Drug Therapy


for CHD and CHD Risk Equivalents

LDL-cholesterol goal: <100 mg/dL


Most patients require drug therapy
First, achieve LDL-cholesterol goal
Second, modify other lipid and non-lipid risk
factors

Patients Hospitalized for Coronary Events or


Procedures
Measure LDL-C within 24 hours
Discharge on LDL-lowering drug if LDL-C 130
mg/dL
Consider LDL-lowering drug if LDL-C is 100129
mg/dL

Drug Therapy for Primary Prevention

First Step
Initiate LDL-lowering drug therapy
(after 3 months of lifestyle therapies)
Usual drug options
Statins
Bile acid sequestrant or nicotinic acid
Continue therapeutic lifestyle changes
Return visit in about 6 weeks

Second Step
Intensify LDL-lowering therapy (if LDL goal not achieved)
Therapeutic options
Higher dose of statin
Statin + bile acid sequestrant
Statin + nicotinic acid
Return visit in about 6 weeks
Third Step
If LDL goal not achieved, intensify drug therapy or refer to
a lipid specialist
Treat other lipid risk factors (if present)
High triglycerides (200 mg/dL)
Low HDL cholesterol (<40 mg/dL)
Monitor response and adherence to therapy
(Q 46 months)

Secondary target of therapy


Non HDL cholesterol
Obesity ( abdominal obesity )
Atherogenic dyslipidemias
Elevated tryglicerides
Small dense LDL
Low HDL- cholesterola

Rised blood pressure


Insulin resistance ( glucose intolerance )
Pro inflammatory
Prothrombotic state

Non-HDL Cholesterol
Non-HDL chol = Total chol HDL chol
Non-HDL chol goal = 30 + LDL-chol goal
As secondary target if tryglicerides are 200
mg/dl
LDL-C Goal
(mg/dL)

Non-HDL-C
Goal (mg/dL)

<100

<130

Multiple (2+) Risk Factors and


10-year risk <20%

<130

<160

01 Risk Factor

<160

<190

Risk Category
CHD and CHD Risk Equivalent
(10-year risk for CHD >20%

Specific Dyslipidemias:
Non-HDL cholesterol
Non-HDL Cholesterol: Secondary Target
Primary target of therapy: LDL cholesterol
Achieve LDL goal before treating non-HDL
cholesterol
Therapeutic approaches to elevated non-HDL
cholesterol
Intensify therapeutic lifestyle changes
Intensify LDL-lowering drug therapy
Nicotinic acid or fibrate therapy to lower VLDL

Management of Very High Triglycerides


(500 mg/dL)

Goal of therapy: prevent acute pancreatitis


Very low fat diets (15% of caloric intake)
Triglyceride-lowering drug usually required
(fibrate or nicotinic acid)
Reduce triglycerides before LDL lowering

Low HDL Cholesterol


Management of Low HDL Cholesterol
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)

Diabetic Dyslipidemia
Lipoprotein pattern: atherogenic
dyslipidemia
(high TG, low HDL, small LDL particles)
LDL-cholesterol goal: <100 mg/dL
Baseline LDL-cholesterol 130 mg/dL
Most patients require LDL-lowering drugs

Baseline LDL-cholesterol 100129 mg/dL


Consider therapeutic options

Baseline triglycerides: 200 mg/dL

Non-HDL cholesterol: secondary target of


therapy