Author
stevit
View
216
Download
0
Embed Size (px)
8/3/2019 16636712-METABOLIK-SINDROME
1/44
8/3/2019 16636712-METABOLIK-SINDROME
2/44
8/3/2019 16636712-METABOLIK-SINDROME
3/44
Metabolic SyndromeClustering of abdominal obesity, dyslipidemiahypertension, and insulin resistence.
Defined as any 3 of the following risk factors(ATP III, 2001
Waist Circumference > 102 cm (men) : > 88cm(women)
HDL
8/3/2019 16636712-METABOLIK-SINDROME
4/44
Clustering Of Abdominal Obesity, dyslipidemia
Hypertension, and Insulin Resistance
Defined as any 3 of the following riskfactors
(ATP III 2001) (Asian Modification) Waist circumference> 90 cm (men) or>80 cm
(Women)
HDL (
8/3/2019 16636712-METABOLIK-SINDROME
5/44
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)
8/3/2019 16636712-METABOLIK-SINDROME
6/44
Metabolic Syndrome : Aetiology Is just a co-incidental clustering of CVD
risk factors?
Is there are asingle aetological determinante.g. genetic, insulin resistance, visceralobesity, endothelial dysfunction orinflammation ?
Are there multiple determinants ?
8/3/2019 16636712-METABOLIK-SINDROME
7/44
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
8/3/2019 16636712-METABOLIK-SINDROME
8/44
Faktor Risiko Kardiovaskular
Kannel WB. In: Genest J, et al, eds. Hypertension: Physiopathology and Treatment. New York, NY: McGraw Hill;1977:888-910.
Dislipidemia
TC 210 mg/dL
Hipertensi
SBP 165 mmHg
Toleransi glukosa
X2.6
X4.5
X3.5 X2.3
Dislipidemia
TC 235 mg/dLHipertensi
SBP 195 mmHg
Merokok
X5.3
X8.7
X5.2 X2.9
X1.9 X1.3
X1.8
X3
X1.7
X1.7
Bila 2 atau lebih faktor risiko bergabung, maka risikoBila 2 atau lebih faktor risiko bergabung, maka risiko
terjadinya CV events menjadi lebih besarterjadinya CV events menjadi lebih besar
8/3/2019 16636712-METABOLIK-SINDROME
9/44
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
8/3/2019 16636712-METABOLIK-SINDROME
10/44
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
8/3/2019 16636712-METABOLIK-SINDROME
11/44
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
8/3/2019 16636712-METABOLIK-SINDROME
12/44
The metabolik syndrome
Genes & evironment Interecting
ENVIRONMENT
Early Life Adult Life- Low birth weight - Sedentory life style
- Poor nutrition - Dietary factor
Metabolik Syndrome
Cardiovascular disease
GENES
8/3/2019 16636712-METABOLIK-SINDROME
13/44
The metabolik syndrome : The epidemic strikes back !!!
High social & ekonomic infact
Globalozation
Modernization
migration
Diabetes & CVD
Risk factorsDiabesity
(Metabolic Syndrome)
Morbidity &
Mortality
8/3/2019 16636712-METABOLIK-SINDROME
14/44
Hipertension Hyperglykemia Obesity Dyslipidemia Microalbuminuria
Metabolik
syndrome
Atherosclerosis
Cardiovascular
disease
Intervention/
Control
Treatment of obesityMultiple risk reducer
8/3/2019 16636712-METABOLIK-SINDROME
15/44
Insulin resistence is linded to cardiovascular
disease
INSULIN RESISTENCE
Hyperglycaemia
Hyperinsulinaemia
Hypertension
Dyslipidaemia
Decraesed fibrinolitic
Octivity ( PAI-1 )
Endothelial dysfunction
Inflammatory markers
Of a the rosclerosis
Mikroalbuminuria
8/3/2019 16636712-METABOLIK-SINDROME
16/44
Gangguan toleransi glukosa berkelanjutan ? Normal TGT Diabetes
Tipe 2 komplikasi kematian
Tahap
Preklinik Klinik Komplikasi
Pencegahan
primerPencegahan
Skunder
PencegahanTertier
8/3/2019 16636712-METABOLIK-SINDROME
17/44
The Cardiovascular Continuum of
EventsCoronaryThrombosis
Myocardial
Ischemia
CAD
Atherosclerosis
Risk Factors
( DyslipidemiaDyslipidemia, o BP, DM,
Insulin Resistance, Platelets,
Fibrinogen, etc) Adapted fromDzau et al. Am Heart J. 1991;121:1244-1263
Arrhythmia and
Loss of Muscle
Remodeling
Ventricular
Dilatation
Congestive
Heart Failure
End-stage
Heart Disease
Primaryprevention
Secondaryprevention
ACS
Stroke
8/3/2019 16636712-METABOLIK-SINDROME
18/44
Myocardial
Ischemia
CAD
Atherosclerosis
Risk Factors
( Dyslipidemia, o BP, DM,
Insulin Resistance, Platelets,
Fibrinogen, etc)Adapted from
Dzau et al. Am Heart J. 1991;121:1244-1263
Primaryprevention
Secondaryprevention
Why primaryWhy primary
prevention ?prevention ?
Kita Akan Fokus Pada
8/3/2019 16636712-METABOLIK-SINDROME
19/44
Primary Prevention Cost-effective
Less painful
Better quality of life
Easier to manage
But..
No symptoms (low compliance)
Investment
8/3/2019 16636712-METABOLIK-SINDROME
20/44
8/3/2019 16636712-METABOLIK-SINDROME
21/44
1. Total cholesterol > 200 mg/dl
2. HDL-C < 40 mg/dl3. Triglyceride > 150mg/dl
4. LDL-C:
> 100 mg/dlCHD and CHD riskequivalent
>130 mg/dl 2
> 160 mg/dl0-1
LDL-CFaktor Resiko
NCEP-ATP III Report. JAMA 2001;285:2486-2497
8/3/2019 16636712-METABOLIK-SINDROME
22/44
NCEP-ATP III Report. JAMA 2001;285:2486-2497
DISLIPIDEMIA LDL Primary target of therapy
Total cholesterol
HDL
TG
8/3/2019 16636712-METABOLIK-SINDROME
23/44
8/3/2019 16636712-METABOLIK-SINDROME
24/44
Atherosclerosis: Penyakit Yang ProgresifAtherosclerosis: Penyakit Yang Progresif
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.
Monocyte LDL-C
Adhesion
molecule
Macrophage
Foam cell
Oxidized
LDL-C
Plaque rupture
Smooth muscle
cells
CRP
Plaque instabilityand thrombus
OxidationInflammationEndothelialdysfunction
8/3/2019 16636712-METABOLIK-SINDROME
25/44
Aterosklerosis Dimulai Sejak Usia Muda
Tuzcu EM, Kapadia SR, Tutar E, et al. High Prevalence ofCoronary Atherosclerosis in Asymptomatic Teenagers And Young Adults: EvidenceFromIntravascular Ultrasound.Circulation 2001;103:2705-2710
8/3/2019 16636712-METABOLIK-SINDROME
26/44
KERUSAKANAPA SAJA YANG BISADISEBABKAN OLEH PLAK?
Coronary artery
Stroke
Deep veinthrombosis (DVT)
Plaque rupturep unstable angina
pMyocardial infarction
(MI) / heart attack
Pulmonary embolism
(PE)
8/3/2019 16636712-METABOLIK-SINDROME
27/44
KERUSAKANAPA SAJA YANG BISADISEBABKAN OLEH PLAK?
Coronary artery
Stroke
Deep veinthrombosis (DVT)
Plaque rupturep unstable angina
pMyocardial infarction
(MI) / heart attack
Pulmonary embolism
(PE)
8/3/2019 16636712-METABOLIK-SINDROME
28/44
From a prospective analysis of 1886 patients aged u62 years, 810 patients were diagnosed with CAD as defined by adocumented clinical history of MI, ECG evidence of Q-wave MI, or typical angina without previous MI. (Adapted
from Aronow et al.)
Atherosclerosis: Penyakit Sistemik
8/3/2019 16636712-METABOLIK-SINDROME
29/44
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
8/3/2019 16636712-METABOLIK-SINDROME
30/44
Mortality from CVD and CHD in Selected Countries
Rate per 100,000 population (men aged 3574 years)
(Adapted from 1998 World Health Statistics)
0
500
1000
1500
Russia Finland England/
Wales
Italy Japan
CVD deaths
CHD deaths
Poland New
Zealand
USA Spain
8/3/2019 16636712-METABOLIK-SINDROME
31/44
0
2
4
6
8
10
12
14
16
18
140 160 180 200 220 240 260 280 300
Serum total cholesterol (mg/dL)
CHD death
rate per
1000 men
Multiple Risk Factor Intervention Trial.
LaRosa et al, 1990
Hubungan Level Kolesterol dengan kematian PenyakitHubungan Level Kolesterol dengan kematian PenyakitJantung KoronerJantung Koroner
8/3/2019 16636712-METABOLIK-SINDROME
32/44
Adapted from: Stamler, J. et al., Diabetes Care 1993; 16: 434-44
hypercholesterolaemia, smoking,
hypertension
140
120
100
00 1 2 3
Faktor Resiko dan KematianFaktor Resiko dan Kematian
Non-diabetics
Diabetics
Cardiovascularm
ortality
(10,0
00person-y
ears)
80
60
40
20
8/3/2019 16636712-METABOLIK-SINDROME
33/44
8/3/2019 16636712-METABOLIK-SINDROME
34/44
NCEP-ATP III Report. JAMA 2001;285:2486-2497
Grundy SM, et al. NCEP Report. Circulation 2004;110:227-239
LDL-C: Primary target of therapy
Total cholesterol < 200 mg/dl
HDL-C > 40 mg/dl
Triglyceride < 150mg/dl
Risk factor LDL-C
0-1 < 160 mg/dl
u 2 < 130 mg/dl
CHD and CHD risk
equivalent
< 100 mg/dl
Very high risk 70 mg/dl
8/3/2019 16636712-METABOLIK-SINDROME
35/44
NCEP-ATP III Re ort. JAMA 2001 285:2486-2497
LDLLDL >> 160 mg/dL160 mg/dL
Gaya hidup sehatGaya hidup sehat
Periksa ulang setiap 1Periksa ulang setiap 1--2th2th
Atau 3Atau 3--5 th bila LDL 190 mg/dL190 mg/dL
Teruskan diet, aktifitas fisikTeruskan diet, aktifitas fisik
Pertimbangkan statinPertimbangkan statin
Periksa ulang 3blnPeriksa ulang 3bln
Mulai statinMulai statin
Periksa ulang 3blnPeriksa ulang 3bln
Sasaran:Sasaran:
LDL < 160 mg/dLLDL < 160 mg/dL
Faktor Risiko 0Faktor Risiko 0--11
LDLLDL >> 160 mg/dL160 mg/dL
LDLLDL160160 189 mg/dL189 mg/dL
8/3/2019 16636712-METABOLIK-SINDROME
36/44
FaktorRisiko >2
LDLLDL >> 130 mg/dL130 mg/dL
LDLLDL >> 130 mg/dL130 mg/dL
Gaya hidup sehatGaya hidup sehat
Periksa ulang setiap 1Periksa ulang setiap 1--2th2th
Cari & obati penyebab sekunderCari & obati penyebab sekunder
LDL < 130 mg/dLLDL < 130 mg/dL
Diet, periksa ulang 3 blnDiet, periksa ulang 3 bln
LDLLDL130130 159 mg/dL159 mg/dL
LDLLDL>>160 mg/dL160 mg/dL
Teruskan diet, aktifitas fisikTeruskan diet, aktifitas fisik
Pertimbangkan statinPertimbangkan statin
Periksa ulang 3blnPeriksa ulang 3bln
Mulai statinMulai statin
Periksa ulang 3blnPeriksa ulang 3bln
Sasaran:Sasaran:
LDL < 130 mg/dLLDL < 130 mg/dLNCEP-ATP III Report. JAMA 2001;285:2486-2497
8/3/2019 16636712-METABOLIK-SINDROME
37/44
Pencegahan PrimerPada Pasien dengan > 2 Faktor Risiko
Mulai dengan obatMulai dengan obat
hipolipidemikhipolipidemik
Mulai dengan statin /Mulai dengan statin /
resin / asam nikotinat,resin / asam nikotinat,teruskan dengan terapiteruskan dengan terapi
non farmakologisnon farmakologis
Bila sasaran LDL blmBila sasaran LDL blm
tercapai, intensifkantercapai, intensifkan
obat hipollipidemikobat hipollipidemik
Tingkatkan dosis statin /Tingkatkan dosis statin /
+ resin / asam nikotinat+ resin / asam nikotinat
Obati faktor rsisiko lipidObati faktor rsisiko lipid
lainnya (TG / HDL)lainnya (TG / HDL)
Bila sasaran LDL blmBila sasaran LDL blmtercapai, intensifkantercapai, intensifkan
obat hipollipidemikobat hipollipidemik
atau rujuk keatau rujuk ke
spesialisspesialis
Pemantauan responsPemantauan respons
dan ketaatan berobatdan ketaatan berobat
6 minggu6 minggu
6minggu
6minggu
Tiap 4Tiap 4--6 bln6 bln
NCEP-ATP III Report. JAMA 2001;285:2486-2497
8/3/2019 16636712-METABOLIK-SINDROME
38/44
PJK Atau Yang Disamakan
LDLLDL >> 100 mg/dL100 mg/dL
Gaya hidup sehatGaya hidup sehat
Periksa ulang setiap 6Periksa ulang setiap 6--12 bln12 bln
Diet & aktifitas fisikDiet & aktifitas fisik
Pertimbangkan statin LDLPertimbangkan statin LDL>>130mg/dL130mg/dL
Diet, periksa ulang 3 blnDiet, periksa ulang 3 bln
LDLLDL >>100 mg/dL100 mg/dL
Berikan StatinBerikan StatinPeriksa ulang 3 blnPeriksa ulang 3 bln
Sasaran:Sasaran:
LDL < 100 mg/dLLDL < 100 mg/dL
NCEP-ATP III Report. JAMA 2001;285:2486-2497
LDL < 100 mg/dLLDL < 100 mg/dL
8/3/2019 16636712-METABOLIK-SINDROME
39/44
COMETS Study Design
LipidshsCRPSafety
LipidshsCRPSafety
LipidshsCRPSafety
ATV 10 mg (n=157)
Placebo (n=79)
RSV 10 mg (n=165)
ATV 20 mg
RSV 20 mg
RSV 20 mgPatients (n=401)
Metabolic syndrome
CHD risk >10%
Statin nave
18 years
Visit:Week:
14
22
30
46
512
Dietary run in/ eligibility
COMETS=COmparative study with rosuvastatin in subjects with METabolicSyndrome; CHD=coronary heart disease; RSV=rosuvastatin; ATV=atorvastatin;hsCRP=high-sensitivity C-reactive protein
Stalenhoef AFH et al. Diabetologia 2004;47 (suppl):A4091147
8/3/2019 16636712-METABOLIK-SINDROME
40/44
COMETS Change in Lipid Profile
at 6 Weeks
***
***
**
***
***
***
******
***43
32
19
41
37
28
21
35
0.3
1.1
0.72.8
0.9
9.5
5.1
50
40
30
20
10
0
10
20
LDL-C HDL-C TC TG nonHDL-C
RSV 10 mg (n=164)ATV 20 mg (n=155)Placebo (n=78)
LSMcha
nge
frombaseline(%)
ITT population by as allocated treatment; **P
8/3/2019 16636712-METABOLIK-SINDROME
41/44
ITT population by as allocated treatment; *P
8/3/2019 16636712-METABOLIK-SINDROME
42/44
Potential Benefits of
Moderate (5-10%) Weight Loss
Subkutaneus Adipose Tissue
Visceral
Adipose Tissue
5-10%
Weight loss23% voceral adivose
Tissue loss physical
Activity pharmacotheraphy
Blood Preasure
Deteriorated lipid profile improved
Impaired Insulin sensitivity ImprovedInsulinaemia alycaemia
Susceptibility to thrombosis
Hight Risk of coronary heart disease low
Imflamation Markers
Reduced Obesity
(Low Waist measure ment)Abdominally
Obese (Hight Waist
Measurement) Despres JP, BMJ. 2001, 322. 716.20.
8/3/2019 16636712-METABOLIK-SINDROME
43/44
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.
8/3/2019 16636712-METABOLIK-SINDROME
44/44