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8/3/2019 16636712-METABOLIK-SINDROME

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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


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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 (


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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)


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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 ?


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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


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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


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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


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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


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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


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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


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The metabolik syndrome : The epidemic strikes back !!!

High social & ekonomic infact

Globalozation

Modernization

migration

Diabetes & CVD

Risk factorsDiabesity

(Metabolic Syndrome)

Morbidity &

Mortality


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Hipertension Hyperglykemia Obesity Dyslipidemia Microalbuminuria

Metabolik

syndrome

Atherosclerosis

Cardiovascular

disease

Intervention/

Control

Treatment of obesityMultiple risk reducer


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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


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Gangguan toleransi glukosa berkelanjutan ? Normal TGT Diabetes

Tipe 2 komplikasi kematian

Tahap

Preklinik Klinik Komplikasi

Pencegahan

primerPencegahan

Skunder

PencegahanTertier


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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


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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


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Primary Prevention Cost-effective

Less painful

Better quality of life

Easier to manage

But..

No symptoms (low compliance)

Investment


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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


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DISLIPIDEMIA LDL Primary target of therapy

Total cholesterol

HDL

TG


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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


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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


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KERUSAKANAPA SAJA YANG BISADISEBABKAN OLEH PLAK?

Coronary artery

Stroke

Deep veinthrombosis (DVT)

Plaque rupturep unstable angina

pMyocardial infarction

(MI) / heart attack

Pulmonary embolism

(PE)


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KERUSAKANAPA SAJA YANG BISADISEBABKAN OLEH PLAK?

Coronary artery

Stroke

Deep veinthrombosis (DVT)

Plaque rupturep unstable angina

pMyocardial infarction

(MI) / heart attack

Pulmonary embolism

(PE)


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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


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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


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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


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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


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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


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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


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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


Sasaran:Sasaran:

LDL < 160 mg/dLLDL < 160 mg/dL

Faktor Risiko 0Faktor Risiko 0--11


LDLLDL160160 189 mg/dL189 mg/dL


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FaktorRisiko >2




Periksa ulang setiap 1Periksa ulang setiap 1--2th2th

Cari & obati penyebab sekunderCari & obati penyebab sekunder


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


Mulai statinMulai statin


Sasaran:Sasaran:

LDL < 130 mg/dLLDL < 130 mg/dLNCEP-ATP III Report. JAMA 2001;285:2486-2497


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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



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PJK Atau Yang Disamakan



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:





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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


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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


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ITT population by as allocated treatment; *P


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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.


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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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