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

Exogenous
Dietary
lipids

Endogenous

Bile
acids
+
Cholesterol
Peripheral
tissues

Chylomicron
remnant

Chylomicron

Capillaries

Capillaries

LDLR
ApoB
ApoE

FFA

FFA

ApoCs
Muscle

Adipose

Muscle

Adipose

Reverse cholesterol
transport

Macrophage

CE

LCAT

VLDL

Liver

TP
E
C

Nascent
HDL

Small
intestine

IDL
TP

LDL

Mature
HDL

LDLR

LDLR

Chylomicrons

Peripheral cells

Free
cholesterol

CE

Apo AI

TG

The density and size-distribution of the major classes of

lipoprotein

0.95
VLDL

Density, g/mL

1.006

IDL
Chylomicron
remnants

1.02
LDL

Chylomicron

1.06
1.10

HDL

1.20
5

10

20

40
Diameter, mm

60

80

1000

The Basic Components of Cholesterol Synthesis and Excretion

Familial
hypercholesterolemia

LDL
receptor

Familial ligand-defective
apolipoprotein B-100
Autosomal recessive
hypercholesterolemia

Bile

Apolipoprotein B-100

LDL

Phospholipids
Cholesterol
ester core

Plasma
Fat
Muscle

ABC G5
ABC G8

Artery

Sitosterolernia
Triglycerides

Very-lowdensiti lipoprotein

Triglycerides

Overview of lipoprotein metabolism with special reference to the

role of HDL-cholesterol

VLDL-C

LIVER
FC
CE

TG

CE
TG

LPL

FFA

CE

LDL-C

FFA
Adipose
tissue

Adipose and
other tissues

TG

CETP

CE

LIVER

LDL-C receptor

LDL-C receptor
CE

TG

HDL-C CE

LCAT

FC

New
synthesis
Cell in
peripheral tissues

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

Atherosclerosis: A Progressive Disease

Plaque rupture

Monocyte

LDL-C

Adhesion
molecule

Macrophage

Oxidized
LDL-C
Foam cell

CRP

Smooth muscle
cells

Endothelial
dysfunction

Inflammation

Oxidation

Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126.

Plaque instability
and thrombus

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