LIPID PLASMA

CH3
C

H
CH3

H
CH2

CH2

CH2

CH3

(CH2)7

CH3

Kolesterol

CH3

HO

H3C

O
CH2

H
C

(CH2)7

(CH2)14

CH3

CH
CH2

Trigliserid
O

(CH2)16

CH3

O
C H2.O.CO.R
R.COO.CH
C H2O

O
P
O

OCH2.CH2.N

CH3
CH3
CH3

Fosfolipid

Pickup J, Williams G. Lipid Disorders in diabetes mellitus. Text Book of Diabetes. 1997:p. 55.1-31

LIPOPROTEIN

Lipid plasma tidak larut dalam air

Untuk melarutkan perlu Apolipoprotein =
Apoprotein = Apo
Kompleks lipid plasma apoprotein
disebut lipoprotein
Lipoprotein = kolesterol, trigliserida,
fosfolipid, dan apoprotein

K
TG

F
Apo

+
=

TG

Apo

Apo

Apo

LIPOPROTEIN

APAKAH LIPOPROTEIN ?

Apolipoprotein + Lipid = Lipoprotein

Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer.

PARTIKEL KOLESTEROL
HDL
Apo A-1

Apo A-2

Apo E
Apo C

Trigliceride

Phospholipid
Cholesterol Ester

Unesterified cholesterol

Diameter : 75-100
Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer. 1996

JENIS LIPOPROTEIN
Lipoprotein
class

Relative size,
triglyceride and
cholesterol content

Chylomicrons

Major
apoproteins
B48, E,
CII

VLDL

B100, E,
CII

IDL

B100, E

LDL

B100

HD
L

AI,AII

Triglyceride

Cholesterol

THE METABOLIC PATHWAY

OF LIPOPROTEINS
Endogenous pathway
Exogenous pathway
Reverse cholesterol
transport

Lipoprotein Metabolism
Liver

VLDL

VLDL

Endogenou
s
IDL

LDL

Macrophage
HDL

Cholesterol

RCTP

remnants

Exogenous
kilomikron

Cholesterol

Food

Intestine

Stool

RCTP = reverse cholesterol

transport pathway

Shepherd J. Eur Heart J Supplements 2001;3(suppl

Reverse cholesterol transport

Liver

LDL Receptor

VLDL

Scavenger receptor-A / CD 36
ABC-1 transporter

VLDL

SRB-1 receptor

IDL
Macrophage

LDL

Triglyceride
Cholesteryl ester

Cholesterol

HDL
Nascent HDL
Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, lowdensity lipoprotein, and triglycerides: A current review. Am J Cardiol 2000; 86:
5L-10L

THE METABOLIC PATHWAY

OF LIPOPROTEIN
IN
TYPE 2 DIABETES MELLITUS
AND
METABOLIC SYNDROME

Lipoprotein Metabolism
in Insulin Resistance
Adipocytes
FFA

Perlemakan
hati
VLDL
large

CE

(CETP)
TG

IR
CE

Insulin
FFA : Free Fatty Acid
CE
: Cholesteryl Ester
CETP : Cholesteryl Ester Transfer
Protein

(CETP)
LDL

HDL

ApoA1

TG
LDL
teroksidasi

Kidney

(lipoprotein or
Hepatic lipase i)

Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein,
and triglycerides: A current review. Am J Cardiol 2000;86:5L-10L

DISLIPIDEMIA
Dislipidemi diabetes tipe 2 / resistensi
insulin
Resistensi

insulin

mengakibatkan
meningkat hati, menjadi sumber VLDL

FFA

VLDLLDL, pertukaran TG dan kolesterol LDL

kecil padat
ApoA1 dikeluarkan oleh ginjal, sehingga HDL
kolesterol rendah

Kesimpulan: TG tinggi, HDL-kol rendah,

LDL-kol padat, kecil tinggi

Management of
dyslipidaemia
All three lipid profiles
-kolesterol LDL, kolesterol HDL, dan
trigliserid

play a role in the formation of

atherosclerosis

Jumlah kematian 10-tahun

(PAK),kematian per 1000

50
40
30
20
10
0
0

150
(3.87)

200
(5.17)

250
(6.46)

300
(7.75)

Kadar serum kolesterol (mg/dl / mmol/L)

Hubungan antara kadar serum kolesterol dan risiko penyakit arteri koroner
Dari penelitian Multiple Risk Factor Intervention Trial (MRFIT)
Farnier M, Davignon J. Am J Cardiol. 1998;82:3J-10J

156
150

Trigliserid < 200 mg/dl

PAK / 1000

Trigliserid > 200 mg/dl

100
73

55

50
10
0

18

17

22

25

130 - 160
160 - 190
> 190
LDL-kolesterol
1000 orang dalam 4 tahun menurut kadar
LDL-kolesterol.

< 130

Insiden PAK /
trigliserid dan

Assman G. Am J Cardiol 1992;70:10H-

120

PROCAM Study

100
80
Insidens PAK
60
(per 1.000 dalam
6 tahun)
40
20
0

< 35

35 - 55
> 55
HDL-kolesterol (mg/dl)

Hubungan HDL-kolesterol dengan insiden penyakit arteri koroner (PAK):

Dari Prospective Cardiovascular Munster (PROCAM) Study.
HDL-kolesterol secara meyakinkan berhubungan dengan risiko PAK ( p <
0.001).

CLASSIFICATION OF
LDL-cholesterol, Totalcholesterol, HDL-cholesterol
and Triglycerides
NCEP-ATP III

KLASIFIKASI TOTAL, LDL, HDLKOLESTEROL, DAN TRIGLISERID MENURUT

NCEP ATP III
LDL kolesterol
< 100
mg/dl
100 129 mg/dl
130 159 mg/dl
160 189 mg/dl
> 190
mg/dl
Total kolesterol
< 200
mg/dl
200 239 mg/dl
> 240
mg/dl
HDL kolesterol
< 40
mg/dl
> 60
mg/dl

Optimal
Mendekati optimal
Sedikit tinggi (Borderline)
Tinggi
Sangat tinggi
Diinginkan
Sedikit tinggi (Borderline)
Tinggi
Rendah
Tinggi

JAMA 2001;285:24862-497

TRIGLISERIDA (NCEP-ATP III)

Optimal

< 150 mg/dl

Sedikit tinggi(borderline)

150 - 199 mg/dl

Tinggi

200 - 499 mg/dl

Sangat tinggi

> 500 mg/dl

Risk assessment: first step

in the management of
dyslipidaemia
Langkah pertama menentukan risiko PKV
seseorang adalah dengan menghitung
berapa faktor risiko yang dimiliki
penderita tersebut (risk assessment)
Faktor risiko dikelompokkan atas tiga
kelompok
risiko rendah, risiko sedang, dan risiko
tinggi

Major Risk Factors (Exclusive of LDLcholesterol) That Modify LDL Goals

Cigarette smoking

Hypertension
mmHg,

(blood pressure > 140/90

or on antihypertension)

Low HDL cholesterol

(< 40 mg/dl)*
Family history of premature (CHD in male first-degree
relative <
55 years; CHD in female
firstdegree relative < 65
years
HDL cholesterol > 60 mg/dl counts as a negative risk
factor,
Age
male > 45 years, female > 55
years
its presence removes 1 risk factor from the total count

JAMA 2001;285:24862-497

Three categories of risk that modify

LDL cholesterol goals
Kelompok risiko

Sasaran LDL
(mg/dl)

Mereka dengan PAK atau yang

disamakan
(risiko tinggi)

< 100

Faktor risiko multipel ( > 2)

(risiko sedang)

< 130

0 - 1 faktor risiko

< 160

(risiko rendah)
JAMA 2001;285:24862-497

Mortality from coronary heart

disease in subjects with type 2
diabetes and in non-diabetic subjects
with and without prior myocardial
infarction
Haffner SM, et al.
N Engl J Med

1998; 339: 229234

50

45,0%

45

7-year incidence of
MI

Non
diabetic

40

Diabeti
c

35
30
25

18,8%

20,2%

No DM, MI

DM, No MI

20
15
10
5
0

3,5%

No DM, No MI

DM, MI

Type 2 diabetes mellitus (DM) and coronary artery disease (CAD). The 7 year
incidence of fatal or nonfatal myocardial infraction (MI) is essentially the
same in patients who have diabetes without a history of CAD and in patients
with CAD who are not diabetic. P < 0,001 for the difference between
patients with and without MI in both group.

PENGERTIAN YANG DISAMAKAN

Penyakit aterosklerotik lain seperti penyakit
arteri perifer, aneurisma aorta abdominalis,
dan penyakit arteri karotis simptomatik
Diabetes melitus terutama tipe 2
Mereka dengan faktor risiko multipel yang
dalam waktu 10 tahun mempunyai risiko PAK
> 20 %

Secara praktis : diabetes melitus, strok,

penyakit arteri perifer

JAMA 2001;285:24862-497

ADULT TREATMENT PANEL REPORTS

ATP III update 2004
Since the publication of ATP III, 5 major clinical trials
with statin therapy and clinical endpoints have been
published
Heart Protection Study (HPS)
Prospective Study of Pravastain in the Elderly at Risk
(PROSPER)
Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial Lipid-Lowering Trial (ALLHAT LLT)
Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering
Arm (ASCOT-LLA)
Pravastatin or Atorvastatin Evaluation and Infection Thrombolysis in Myocardial Infraction 22 (PROVE IT-TIMI 22)
Primary Prevention of Cardiovascular Disease With Atorvastatin in Type 2 Diabetes in the Collaborative Atorvastatin
Diabetes Study (CADRS)

PREVENTION OF CORONARY HEART

DISEASE IN TYPE 2 DIABETES
MELLITUS
Heart Protection Study with Simvastatin
40 mg

RESULTS
Lowering LDL-cholesterol
from < 116 mg/dl to < 77
mg/dl

The lower the better ?

HEART PROTECTION STUDY WITH

SIMVASTATIN (HPS)
Baseline LDLC (mg/dl)

Statin
(n
=10,269)

Placebo
(n =10,267)

< 100

282 (16.4%)

358 (21.0%)

100 129

668 (18.9%)

871 (24.7%)

> 130

1,083
(21.6%)

1,356 (26.9%)

All
patients

2,033
(19.8%)

Event Rate
Ratio

2,585 (25.2%)

0.4

Statin
Worse

Statin
Better

0.76 (0.72 0.81)

p<0.0001
0.6

0.8

1.0

1.2

1.4

Major vascular events by baseline low-density lipoprotein cholesterol (LDLC) level in the Heart Protection Study (HPS). Numbers in parentheses
represent event rates for the subset of 3,421 patients with entry LDL-C
levels < 100 mg/dl (2.6 mmol/l). See Figure 1 for an explanation of event
rate ratio figures. CI = confidence interval.
Ballantyne CM. Am J Cardiol 2003;92 (suppl):3K-9K

PREVENTION OF CORONARY HEART

DISEASE IN TYPE 2 DIABETES
MELLITUS
Heart Protection Study with
Simvastatin

Conclusions
The present study provides direct evidence
that cholesterol-lowering therapy is beneficial
for people with diabetes even if they do not
already have manifest coronary disease or
high cholesterol concentrations
Statin therapy should now be considered
routinely for all diabetic patients at sufficiently
high risk of major vascular events, irrespective
of their initial cholesterol concentrations

PROVE - IT
C-REACTIVE PROTEIN LEVELS AND
OUTCOMES
AFTER
STATIN
THERAPY
Ridker PM, Cannon CP, Morrow D, Rifai N, Lynda M, Rose MS,
Carolyn H, McCabe BS, Preffer MA, Braunwald E.
N Engl J Med 2005; 352: 20 28

Subjects and methods

From the PROVE IT study
Divided into two groups:
LDL cholesterol
> 70 mg/dl
< 70 mg/dl
hsCRP > 2 mg/L
< 2 mg/L
Is there a difference in recurrent
myocardial infarction and death from
coronary causes between these groups?

RATIONAL FOR OPTIMAL VERY

LOW LDL-CHOLESTEROL GOAL (<
70mg/dl)

Lesson from HPS

Lesson from PROVE IT study
A question raised from these studies:
is LDL-C < 100 mg/dl sufficient low in
high-risk patients who already have low
LDL-C
at base line?

WHAT ARE NEW?

Circulation. July, 2004;110:227-239

THE VERY HIGH RISK PATIENTS

Established CVD plus:
1. Multiple

major
diabetes)

risk

factors

(especially

2. Severe and poorly controlled risk factors

(especially continued cigarette smoking)
3. Multiple risk factors of the metabolic
syndrome (especially high triglycerides > 200
mg/dl plus non-HDL-C > 130 mg/dl with low
HDL-C < 40 mg/dl
4. On the basis of PROVE IT, patients with acute
Grundy
SM et al.
Circulation. July, 2004; 110:
coronary
syndromes
227-239

PENATALAKSANAA
N

Perubahan gaya hidup

(therapeutic lifestyle changes )

Perencanaan makan (diet)
Olahraga
Berhenti merokok
Batasi alkohol

Obat penurun lipid

OLAHRAGA
TERATUR

OBAT PENURUN
Persentasi LIPID
penurunan LDL-kolesterol

trigliserid, serta kenaikan HDL-kolesterol

dan

Obat

LDL-K

HDL-K

TG

Statin

18 - 55%

5 - 15%

7 - 30%

Resin

15 - 30%

3 - 5%

- /

Fibrat*

5 - 25%*

10 - 20%*

20 - 50%*

Asam nikotinik

5 - 25%

15 - 35%

20 - 50%

Ezetimibel

10 - 15%

* bezafibrat, cipofibrat dan fenofibrat menurunkan LDL-kolesterol

lebih banyak daripada gemfibrozil

SASARAN LDL - KOLESTEROL

PENGOBATAN PERUBAHAN GAYA HIDUP
(DIET, OLAHRAGA), DAN PENGOBATAN
STATIN
Kelas
risiko

Sasaran
LDL
(mg/dl)

Kadar LDL
dimana dimulai
diet - olahraga
(mg/dl)
> 100

Kadar LDLdimana
dimulai obat
(mg/dl)

PAK atau
yang
disamakan

<
100

> 130

> 2 faktor
risiko

<
130

> 130

> 160

0 - 1 faktor
risiko

<
160

> 160

> 190

(100-129 dapat
dipertimbangk
an obat)

JAMA 2001;285:2487-2497

CONTOH KASUS (1)

Pria umur 50 tahun, ke dokter untuk
pemeriksaan kesehatan. Ia tidak merokok,
melakukan olah raga teratur. Kedua orang
tua masih hidup.
Pada pemeriksaan ditemukan sbb: TB 150
cm, BB 76 kg, TD 185/95 mmHg.
Pemeriksaan fisik lain baik
Ia membawa hasil laboratorium sbb:
pemeriksaan rutin baik, GDP 124 mg/dl,
total -kol 198 mg/dl, LDL- kol 138 mgdl,
HDL 50 mg/dl, TG 156 mg/dl.
Diagnosa? Berapa sasaran LDL-kol?

CONTOH KASUS (2)

Wanita umur 56 tahun, ke dokter untuk
pemeriksaan kesehatan. Ia tidak merokok,
melakukan olah raga teratur. Kedua orang tua
masih hidup.
Pada pemeriksaan ditemukan sbb: TB 150 cm, BB
65 kg, TD 150/90 mmHg. Pemeriksaan fisik lain
baik
Ia membawa hasil laboratorium sbb: pemeriksaan
reduksi positif, GDP 256 mg/dl, A1C 9,0%, total
-kol 180 mg/dl, LDL- kol 110 mg/dl, HDL 50 mg/dl,
TG 156 mg/dl.
Diagnosa? Berapa sasaran LDL-kol?