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METABOLIK SINDROME

Dr. I Gede Palgunadi, Sp.PD


SMF Ilmu Penyakit Dalam
RSUP NTB

Metabolic Syndrome
Clustering of abdominal obesity, dyslipidemia
hypertension, and insulin resistence.
Defined as any 3 of the following risk factors
(ATP III, 2001

Waist Circumference > 102 cm (men) : > 88cm


(women)
HDL<40mg/dl (men) : <50mg/dl (Women)
TG 150 mg/dl
Bp 130/ 85mm Hg
FgG 110 mg/dl

Clustering Of Abdominal Obesity, dyslipidemia


Hypertension, and Insulin Resistance
Defined as any 3 of the following risk
factors
(ATP III 2001) (Asian Modification)

Waist circumference> 90 cm (men) or>80 cm


(Women)
HDL (<40 mg/dl (men) :<50 mg/dl (women)
TG 150 mg/dl
Bp 130/ 85 mm Hg
FPG 110 mg/d/

Metabolik Syndrome (WHO Definition)


Type 2 DM. Impaired glucose tolerance (IGT) or
normal glucose tolerance with insulin resistence
together with 2 of the following
- Eleveted blood pressure 140/90 mm/hg
- Abdominal obesity and/or BML > 30Kg/m2
WHR >0,9 men
>0,8 women
- Low HDL cholesterol < 0,9 mmol/2 (men)
< 1.0 mmol/2 (women)
- High trigly cerides
> 1,7 mmol /2
- Microalbuminuria (AER 20 g/min
or A/C 20mg/g)

Metabolic Syndrome : Aetiology

Is just a co-incidental clustering of CVD


risk factors?
Is there are asingle aetological determinant
e.g. genetic, insulin resistance, visceral
obesity, endothelial dysfunction or
inflammation ?
Are there multiple determinants ?

CVD morbidity & mortality & the metabolik


syndrome (botnia study : 35-70 years)

Metabolik syndrome seen in :


- 10% females & 15% males with NGT (N=1988)
- 42% & 86% with IFG/IGT (N=798)
- 78% & 84% with type 2 diabetes (N=1697)
3-fold increase risk for CHD stroke in people
with metabolik syndrome (P<0.0001)
CVD mortality markedly increased in subjects with the
metabolik syndrome in 6.9 years follow up
(12% < 2.2 %, P<0.001)
Mikroalbuminuria confered highest risk of CVD death
RR 2.8 P= 0.002)

Faktor Risiko Kardiovaskular


Hipertensi
SBP 165 mmHg
X2.6
X1.9
X3.5

Dislipidemia
TC 210 mg/dL
X1.3

X4.5
X2.3

Toleransi glukosa
X1.8

Hipertensi
SBP 195 mmHg
X3
X5.2

X5.3
X8.7

Dislipidemia
TC 235 mg/dL
X1.7
X2.9

Merokok
X1.7

Bila 2 atau lebih faktor risiko bergabung, maka risiko


terjadinya CV events menjadi lebih besar
Kannel WB. In: Genest J, et al, eds. Hypertension: Physiopathology and Treatment. New York, NY: McGraw
Hill;1977:888-910.

Perubahan Fisiologis Terkait Resistansi


Insulin (I)

Ganguan toleransi glukosa


- Impaired fasting glukose
- Impaired glukose tolerance
Ganguan metabolisme asam urat
- Palsma uric asid concentration
- Renal uric acid clearance

Perubahan Fisiologis Terkait resistensi


insulin (2)

Perubahan hemodinamik :
- Symphotettic nervous system activity
- Renal sodium retention
- Blood pressure(~50% of patient with
hypertention are insulin resistent )
Ganguan hemostatis
- Plasminigen activator inhibitor I
- Fibrinogen

Disfungsi Endotel :
- Mononuclear cell adhesion
- Plasma concentration of celular
nadhesion molecules
- Plasma concentration of acymmetric
dimethyl arginine
- Endothelial-dependent vosodilation
Sistim reproduksi
- Polycystic ovary syndrome

The metabolik syndrome


Genes & evironment Interecting
ENVIRONMENT

Early Life

Adult Life

- Low birth weight


- Poor nutrition

- Sedentory life style


- Dietary factor

Metabolik Syndrome
Cardiovascular disease

GENES

The metabolik syndrome :

The epidemic strikes back !!!


High social & ekonomic infact
Globalozation
Modernization
migration
Morbidity &
Mortality

Diabesity
(Metabolic Syndrome)

Diabetes & CVD


Risk factors

Hipertension

Hyperglykemia

Obesity

Dyslipidemia

Metabolik
syndrome
Intervention/
Control

Atherosclerosis
Cardiovascular
disease

Treatment of obesity
Multiple risk reducer

Microalbuminuria

Insulin resistence is linded to cardiovascular


disease
Hyperglycaemia
Hyperinsulinaemia
Hypertension
Dyslipidaemia

INSULIN RESISTENCE

Decraesed fibrinolitic
Octivity ( PAI-1 )
Endothelial dysfunction
Inflammatory markers
Of a the rosclerosis

Mikroalbuminuria

Gangguan toleransi glukosa berkelanjutan ?

Normal

TGT

Diabetes
Tipe 2 komplikasi

kematian

Tahap
Preklinik

Klinik

Komplikasi

Pencegahan
primer

Pencegahan
Skunder

Pencegahan
Tertier

The Cardiovascular Continuum of


ACS

Secondary
prevention

Coronary
Thrombosis

Events
Stroke

Myocardial
Ischemia

CAD
Atherosclerosis
Primary
prevention

Risk Factors
( Dyslipidemia,
Dyslipidemia BP, DM,
Insulin Resistance, Platelets,
Fibrinogen, etc)

Arrhythmia and
Loss of Muscle
Remodeling

Ventricular
Dilatation
Congestive
Heart Failure
End-stage
Heart Disease
Adapted from
Dzau et al. Am Heart J. 1991;121:1244-1263

Kita Akan Fokus Pada


Secondary
prevention
Myocardial
Ischemia

Why primary
prevention ?

CAD
Atherosclerosis
Primary
prevention

Risk Factors
( Dyslipidemia, BP, DM,
Insulin Resistance, Platelets,
Fibrinogen, etc)

Adapted from
Dzau et al. Am Heart J. 1991;121:1244-1263

Primary Prevention
Cost-effective
Less

painful
Better quality of life
Easier to manage
But..

No symptoms (low compliance)


Investment

Klasifikasi:

Dislipidemia Primer: Akibat kelainan genetik


Dislipidemia sekunder: Akibat penyakit lain
1.Hipotiroidisme
2.Sindroma nefrotik
3.Diabetes mellitus
4.Sindroma metabolik
5.Obat2: kortikosteroid, beta-blockers,
progestin.

Pemeriksaan

Umur > 20th (skrining)


Lipid yg diperiksa:
Kolesterol total
Kolesterol HDL
Kolesterol LDL
Trigliseride (puasa 12 16 jam)
Rms Friedewald LDL= Kol T- HDL TG/5
(bila Trigliseride < 400mg/dl)

DISLIPIDEMIA

Resiko rendah (0 1 faktor resiko)


Resiko multipel (2 > faktor resiko)
Resiko tinggi (riwayat PJK, DM, PAD,
stroke)
Resiko sangat tinggi(ACS, sindrome
metabolik, PJK & DM, CKD).

NCEP-ATP III Report. JAMA 2001;285:2486-2497

1.
2.
3.
4.

Total cholesterol > 200 mg/dl


HDL-C < 40 mg/dl
Triglyceride > 150mg/dl
LDL-C:
Faktor Resiko

LDL-C

0-1

> 160 mg/dl

>130 mg/dl

CHD and CHD risk


equivalent

> 100 mg/dl

NCEP-ATP III Report. JAMA 2001;285:2486-2497

Atherosclerosis: Penyakit Yang Progresif


Plaque rupture

Monocyte

LDL-C

Adhesion
molecule

Macrophage

Oxidized
LDL-C
Foam cell

CRP

Smooth muscle
cells

Endothelial
dysfunction

Inflammation

Oxidation

CRP=C-reactive protein; LDL-C=low-density lipoprotein cholesterol.


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

Plaque instability
and thrombus

Aterosklerosis Dimulai Sejak Usia Muda

Tuzcu EM, Kapadia SR, Tutar E, et al. High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers And Young Adults: EvidenceFrom
Intravascular Ultrasound. Circulation 2001;103:2705-2710

KERUSAKAN APA SAJA YANG BISA


DISEBABKAN OLEH PLAK?
Stroke
Coronary artery
Plaque rupture
unstable angina
Myocardial infarction
(MI) / heart attack

Pulmonary embolism
(PE)

Deep vein
thrombosis (DVT)

KERUSAKAN APA SAJA YANG BISA


DISEBABKAN OLEH PLAK?
Stroke
Coronary artery
Plaque rupture
unstable angina
Myocardial infarction
(MI) / heart attack

Pulmonary embolism
(PE)

Deep vein
thrombosis (DVT)

Atherosclerosis: Penyakit Sistemik

From a prospective analysis of 1886 patients aged 62 years, 810 patients were diagnosed with CAD as defined by a
documented clinical history of MI, ECG evidence of Q-wave MI, or typical angina without previous MI. (Adapted
from Aronow et al.)

Coronary Artery Disease (CAD):


Diagnosa Sering Terlambat

Murabito JM, Evans JC, Larson MG, et al. Prognosis After the Onset of Coronary Heart Disease. An Investigation of Differences In
Outcome Between the Sexes According To Initial Coronary Disease Presentation. Circulation 1993;88:2548-2555

Mortality from CVD and CHD in Selected Countries


Rate per 100,000 population (men aged 3574 years)
1500

CVD deaths
CHD deaths

1000

500

0
Russia Poland Finland New England/ USA
Zealand Wales

Italy

Spain

Japan

(Adapted from 1998 World Health Statistics)

Hubungan Level Kolesterol dengan kematian Penyakit


Jantung Koroner

Multiple Risk Factor Intervention Trial.


LaRosa et al, 1990

Cardiovascular mortality
(10,000 person-years)

Faktor Resiko dan Kematian


140
120

Diabetics

100
80
60
40

Non-diabetics

20
0
0

hypercholesterolaemia, smoking,
hypertension
Adapted from: Stamler, J. et al., Diabetes Care 1993; 16: 434-44

LDL-C: Primary target of therapy

Risk factor

LDL-C

0-1

< 160
mg/dl

< 130
mg/dl

CHD and CHD risk

< 100
mg/dl

Total cholesterol < 200 mg/dl


equivalent
HDL-C > 40 mg/dl
Triglyceride
< 150mg/dl
Very
high risk

70 mg/dl

NCEP-ATP III Report. JAMA 2001;285:2486-2497


Grundy SM, et al. NCEP Report. Circulation 2004;110:227-239

Faktor Risiko 0-1


LDL < 160 mg/dL

LDL > 160 mg/dL

Gaya hidup sehat


Periksa ulang setiap 1-2th
Atau 3-5 th bila LDL <130 mg/dL

Cari & obati penyebab sekunder

LDL > 160 mg/dL

Diet, periksa ulang 3 bln


LDL
160 189 mg/dL

LDL
>190 mg/dL

Teruskan diet, aktifitas fisik


Pertimbangkan statin
Periksa ulang 3bln

Mulai statin
Periksa ulang 3bln

Sasaran:
LDL < 160 mg/dL

Faktor Risiko >2


LDL < 130 mg/dL

LDL > 130 mg/dL

Gaya hidup sehat


Periksa ulang setiap 1-2th

Cari & obati penyebab sekunder

LDL > 130 mg/dL

Diet, periksa ulang 3 bln

NCEP-ATP III Report. JAMA 2001;285:2486-2497

LDL
130 159 mg/dL

LDL
>160 mg/dL

Teruskan diet, aktifitas fisik


Pertimbangkan statin
Periksa ulang 3bln

Mulai statin
Periksa ulang 3bln

Sasaran:
LDL < 130 mg/dL

Pencegahan Primer
Pada Pasien dengan > 2 Faktor Risiko
Mulai dengan obat
hipolipidemik

6 minggu

Mulai dengan statin /


resin / asam nikotinat,
teruskan dengan terapi
non farmakologis

Tingkatkan dosis statin /


+ resin / asam nikotinat
6 minggu

Pemantauan respons
dan ketaatan berobat

Bila sasaran LDL blm


tercapai, intensifkan
obat hipollipidemik

Tiap 4-6 bln

Bila sasaran LDL blm


tercapai, intensifkan
obat hipollipidemik
atau rujuk ke
spesialis
Obati faktor rsisiko lipid
lainnya (TG / HDL)

NCEP-ATP III Report. JAMA 2001;285:2486-2497

PJK Atau Yang Disamakan


LDL < 100 mg/dL

Gaya hidup sehat


Periksa ulang setiap 6-12 bln

LDL > 100 mg/dL

Diet & aktifitas fisik


Pertimbangkan statin LDL>130mg/dL

Diet, periksa ulang 3 bln

LDL >100 mg/dL


Berikan Statin
Periksa ulang 3 bln

Sasaran:
LDL < 100 mg/dL
NCEP-ATP III Report. JAMA 2001;285:2486-2497

COMETS Study Design


Patients (n=401)

RSV 10 mg (n=165)

RSV 20 mg

ATV 10 mg (n=157)

ATV 20 mg

Placebo (n=79)

RSV 20 mg

Metabolic syndrome
CHD risk >10%
Statin nave
18 years

Visit:
1
Week: 4

2
2

Dietary run in/ eligibility

3
0

4
6

5
12

Lipids
hsCRP
Safety

Lipids
hsCRP
Safety

Lipids
hsCRP
Safety

COMETS=COmparative study with rosuvastatin in subjects with METabolic


Syndrome; CHD=coronary heart disease; RSV=rosuvastatin; ATV=atorvastatin;
hsCRP=high-sensitivity C-reactive protein

Stalenhoef AFH et al. Diabetologia 2004;47 (suppl):A4091147

COMETS Change in Lipid Profile


at 6 Weeks
RSV 10 mg (n=164)
ATV 20 mg (n=155)
Placebo (n=78)

LSM change
from baseline (%)

20
9.5

10
0
10

**
5.1***
1.1
0.7
***

0.3
***

20

19

30
40

2.8
***

0.9
***

21

28
32 ***

35
***
41

37
***
43

50
LDL-C

HDL-C

TC

TG

nonHDL-C

ITT population by as allocated treatment; **P<0.01, ***P<0.001 vs RSV

Stalenhoef AFH et al. Diabetologia 2004;47 (suppl):A4091147

COMETS Achievement of

NCEP ATP III LDL-C Goals


Patients at goal (%)

100

91
83

80

***
79

*
72

60
40
20
0

***
10
n=164

n=155

n=78

RSV
10 mg

ATV
10 mg

Placebo

6 weeks

n=242

n=155

RSV
ATV
combined 10/20 mg

12 weeks

ITT population by as allocated treatment; *P<0.05, ***P<0.001 vs RSV at same time point

Stalenhoef AFH et al. Diabetologia 2004;47 (suppl):A4091147

Potential Benefits of
Moderate (5-10%) Weight Loss
Subkutaneus Adipose Tissue
5-10%
Weight loss

Visceral
Adipose Tissue

23% voceral adivose


Tissue loss physical
Activity pharmacotheraphy

Blood Preasure
Deteriorated lipid profile improved
Impaired

Insulin sensitivity

Improved

Insulinaemia alycaemia

Susceptibility to thrombosis

Imflamation Markers
Abdominally
Obese (Hight Waist
Measurement)

Hight Risk of coronary heart disease low


Despres JP, BMJ. 2001, 322. 716.20.

Reduced Obesity
(Low Waist measure ment)

Obat Hipolipidemik

Resin: Kolestiramin & Kolestipol


Asam Nikotinat
Statin: Fluvastatin, Lovastatin, Pravastatin,
Simvastatin, Atorvastatin, Rosuvastatin,
Pitavastatin.
Asam Fibrat: Fenofibrat & Gemfibrozil.
Penghambat absorpsi kolesterol: Ezetimibe

KESIMPULAN

Metabolik sindrom bukan satu penyakit


kumpulan fenomena klinis terkait resistensi
insulin
Metabolik sindrom
risiko tinggi PKV
Intervensi terhadap metabolik sindrom termasuk
penurunan berat badan (perubahan gaya hidup,
obat) dapat menunda ataupun mencegah DM
tipe 2 serta menurunkan resiko PKV.
Pengidap Diabetes mempunyai resiko yg
disamakan dg penderita PJK.

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