METABOLIK SINDROME

Dr. I Gede Palgunadi, Sp.PD

SMF Ilmu Penyakit Dalam
RSU Mataram
Disampaikan Pada Acara Siang Klinik
Optimal Lipid Management”
Implementing an effective strategi
For patients
Sabtu, 24 Maret 2007
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 µ 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 Dislipidemia
SBP 165 mmHg TC 210 mg/dL Hipertensi Dislipidemia
X2.6 SBP 195 mmHg X5.3 TC 235 mg/dL
X1.9 X1.3
X4.5 X3 X8.7 X1.7
X3.5 X2.3 X5.2 X2.9

Toleransi glukosa Merokok
X1.8 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 - Sedentory life style
- Poor nutrition - Dietary factor

Metabolik Syndrome GENES

Cardiovascular disease
The metabolik syndrome :
 The epidemic strikes back !!!
High social & ekonomic infact
Globalozation
Modernization
migration
Morbidity &
Mortality

Diabetes & CVD

Risk factors
Diabesity
(Metabolic Syndrome)
Hipertension Hyperglykemia Obesity Dyslipidemia Microalbuminuria

Metabolik
syndrome

Intervention/ Atherosclerosis
Control

Cardiovascular
disease

Treatment of obesity
Multiple risk reducer
Insulin resistence is linded to cardiovascular
disease
Hyperglycaemia

Hyperinsulinaemia

Hypertension

Dyslipidaemia

Decraesed fibrinolitic
INSULIN RESISTENCE 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 Pencegahan
Pencegahan
primer Tertier
Skunder
 The Cardiovascular Continuum of
ACS

Secondary
Coronary
Thrombosis
Events Arrhythmia and
prevention Stroke Loss of Muscle

Myocardial Remodeling
Ischemia

Ventricular
CAD Dilatation

Atherosclerosis Congestive
Heart Failure
Primary
prevention End-stage
Risk Factors
Dyslipidemia ↑ BP, DM,
( Dyslipidemia, Heart Disease
Insulin Resistance, Platelets,
Adapted from
Fibrinogen, etc) 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,
Adapted from
Fibrinogen, etc) 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”
1. Total cholesterol > 200 mg/dl
2. HDL-C < 40 mg/dl
3. Triglyceride > 150mg/dl
4. LDL-C:

Faktor Resiko LDL-C

0-1 > 160 mg/dl

³ 2 >130 mg/dl

CHD and CHD risk

> 100 mg/dl
equivalent

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

DISLIPIDEMIA
 LDL  Primary target of therapy
 Total cholesterol

 HDL

 TG

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

Atherosclerosis: Penyakit Yang Progresif
Plaque rupture

Adhesion Macrophage
Oxidized
Monocyte LDL-C molecule
LDL-C
Foam cell
CRP

Smooth muscle
cells

Endothelial Plaque instability

Inflammation Oxidation
dysfunction and thrombus

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.
 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 Pulmonary embolism
→ Myocardial infarction (PE)
(MI) / heart attack

Deep vein
thrombosis (DVT)
 KERUSAKAN APA SAJA YANG BISA
DISEBABKAN OLEH PLAK?
Stroke

Coronary artery
• Plaque rupture
→ unstable angina Pulmonary embolism
→ Myocardial infarction (PE)
(MI) / heart attack

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 35–74 years)
1500
CVD deaths
CHD deaths

1000

500

0
Russia Poland Finland New England/ USA Italy Spain Japan
Zealand Wales

(Adapted from 1998 World Health Statistics)

Hubungan Level Kolesterol dengan kematian Penyakit
Jantung Koroner
18
16
14
12
CHD death 10
rate per
8
1000 men
6
4
2
0
140 160 180 200 220 240 260 280 300
Serum total cholesterol (mg/dL)

Multiple Risk Factor Intervention Trial.

LaRosa et al, 1990
Faktor Resiko dan Kematian
140
Cardiovascular mortality
(10,000 person-years)

120
Diabetics
100

80

60
40
Non-diabetics
20

0
0 1 2 3

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

≥ 2 mg/dl
< 130
CHD and CHD risk mg/dl
< 100
equivalent mg/dl

Very high risk 70 mg/dl

 Total cholesterol < 200 mg/dl

 HDL-C > 40 mg/dl
 Triglyceride < 150mg/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

Cari & obati penyebab sekunder
Periksa ulang setiap 1-2th
Atau 3-5 th bila LDL <130 mg/dL

LDL > 160 mg/dL

Diet, periksa ulang 3 bln

LDL LDL
160 – 189 mg/dL >190 mg/dL

• Teruskan diet, aktifitas fisik

• Mulai statin
• Pertimbangkan statin
• Periksa ulang 3bln
• Periksa ulang 3bln

Sasaran:
LDL < 160 mg/dL
 Faktor Risiko >2
LDL < 130 mg/dL LDL > 130 mg/dL

Gaya hidup sehat Cari & obati penyebab sekunder

Periksa ulang setiap 1-2th

LDL > 130 mg/dL

Diet, periksa ulang 3 bln

LDL LDL
130 – 159 mg/dL >160 mg/dL

• Teruskan diet, aktifitas fisik

• Mulai statin
• Pertimbangkan statin
• Periksa ulang 3bln
• Periksa ulang 3bln

Sasaran:
NCEP-ATP III Report. JAMA 2001;285:2486-2497 LDL < 130 mg/dL
 Pencegahan Primer
Pada Pasien dengan > 2 Faktor Risiko

Mulai dengan obat Bila sasaran LDL blm

hipolipidemik
Mulai dengan statin /
resin / asam nikotinat,
teruskan dengan terapi
non farmakologis
6 minggu tercapai, intensifkan
obat hipollipidemik
Tingkatkan dosis statin /
+ resin / asam nikotinat

6 minggu
Bila sasaran LDL blm
Pemantauan respons tercapai, intensifkan
dan ketaatan berobat Tiap 4-6 bln 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 LDL > 100 mg/dL

Gaya hidup sehat Diet & aktifitas fisik

Periksa ulang setiap 6-12 bln 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
RSV 10 mg (n=165) RSV 20 mg
Patients (n=401)
Metabolic syndrome
CHD risk >10% ATV 10 mg (n=157) ATV 20 mg
Statin naïve
≥18 years
Placebo (n=79) RSV 20 mg

Visit: 1 2 3 4 5
Week: –4 –2 0 6 12

Dietary run in/ eligibility Lipids Lipids Lipids

hsCRP hsCRP hsCRP
Safety Safety 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):A409–1147

 COMETS – Change in Lipid Profile
at 6 Weeks†
20 RSV 10 mg (n=164)
ATV 20 mg (n=155)
9.5 Placebo (n=78)
10 **
5.1***
from baseline (%)

1.1
0 –0.7
–0.3
LSM change

–0.9
*** *** –2.8
***
–10 ***

–20 –19
–21

–30 –28
–32 ***
–37 –35
–40 ***
*** –41
–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):A409–1147

 COMETS – Achievement of
NCEP ATP III LDL-C Goals†
100
91
***
83
Patients at goal (%)

* 79
80 72

60

40

20 ***
10

n=164 n=155 n=78 n=242 n=155

0
RSV ATV Placebo RSV ATV
10 mg 10 mg combined 10/20 mg
6 weeks 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):A409–1147

 Potential Benefits of
Moderate (5-10%) Weight Loss
Subkutaneus Adipose Tissue
5-10%
Visceral Weight loss
Adipose Tissue 23% voceral adivose
Tissue loss physical
Activity pharmacotheraphy

Blood Preasure

Deteriorated lipid profile improved

Insulin sensitivity
Impaired Improved
Insulinaemia alycaemia

Susceptibility to thrombosis

Imflamation Markers
Abdominally Reduced Obesity
Obese (Hight Waist Hight Risk of coronary heart disease low (Low Waist measure ment)
Measurement) Despres JP, BMJ. 2001, 322. 716.20.
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.