Curriculum vitae

• Nama : Em Yunir
• Tempat/tanggal lahir : Jakarta/ 9 Juni 1962
• Agama : Islam
• Lulus Fakultas kedokteran Universitas Indonesia tahun 1988
• Lulus Spesialis Ilmu Penyakit Dalam FKUI tahun 2000
• Program Konsultan Metabolik Endokrin tahan 2000
• Staf Divisi Metabolik Endokrin Departemen Ilmu Penyakit Dalam
Fakultas Kedokteran Universitas Indonesia
• Poli klinik Diabetes Terpadu Rumah sakit Marzoeki Mahdi Bogor

Organisasi :
• Sekjen Persadia Tahun 2005 -2008
• PERKENI
• PEDI
• PAPDI
 FAKTOR-FAKTOR RISIKO
PENYAKIT JANTUNG DAN PEMBULUH DARAH

EM YUNIR
DIVISI METABOLIK DAN ENDOKRIN
FKUI/RSUPN CIPTOMANGUNKUSUMO
Penyakit Jantung Pembuluh Darah

Jantung dan
d
pembuluh Stroke
darah jantung

PAD
Penyakit jantung pembuluh
darah mempunyai risiko
kematian yang sama besar
d
dengan di b t melitus
diabetes lit
 7-Year Incidence of Fatal/Nonfatal MI
From the East-West Study

50 45†
45 Nondiabetic (n=1373)
nfarction (%)

Diabetic (n=1059)
e of

40
ence Rate

35
30
25 20.2
18 8*
18.8
ocardial In
ear Incide

20
15
10
5 3.5
7-ye
Myo

0
No DM, no MI No DM, MI DM, no MI DM, MI

* p<0.001 vs. nondiabetic, no MI

† p<0.001 vs. diabetic, no MI

Haffner SM et al. N Engl J Med 1998;339:229-34.

Penyakit Jantung dan pembuluh
d h
darah
Penyebab utama kematian di US

Penyebab
y 40 % angka
g kematian CVD

1/3 diantaranya kematian premature

Suddent death usia 15-34 tahunÏ

Angka kecacatan >>

CDCP 2007
 Diabetes Melitus
Meningkatkan risiko kematian

Meningkatkan angka kesakitan

Komplikasi
p kronis

Kecacatan
Penurunan kwalitas hidup

ADA 2008
Cardiometabolic Risk

Sekelompok faktor risiko terhadap

munculnya
l penyakitkit jantung
j t d
dan
diabetes tipe 2 di kemudian hari

Beberapa faktor risiko dapat

dimodifikasi untuk pencegahan
 Faktor-faktor
Faktor faktor risiko kardiometabolik

Dapat
p dimodifikasi Tidak dapat
p dimodifikasi
• Berat badan lebih/obesitas •Umur

• Gula darah diatas normal •Etnis/suku bangsa

• Dislipidemia :kolesterol LDL Ï, •Jenis kelamin
HDL Ð, Trigliserida Ï
• Tekanan darah tinggi •Keturunan
• Hiperkoagulasi
• Inflamasi
• Merokok
• Kurang aktivitas
• Pola makan tidak sehat
 Overweight / Obesity
Age Genetics

Insulin
Abnormal lipid
Resistance
Insulin
su resistance
es sta ce syndrome
sy d o e metabolism
•LDL ↑
↑ ? •Apo-B ↑
Lipids
p ↑BP ↑Glucose •HDL-C ↓
•TG ↑

Cardiometabolic risk Age race

Age, race,
Global diabetes / CVD risk sex,
family history

Smoking
Physical activity Inflammation
Hypercoagulatio
Elevated blood n Management in Patients
Brunzell JD et al. Lipoprotein
with Cardiometabolic Risk. J Am Coll Cardiol
pressure 2008;51:1512-24.
1. Diabetes
Risk of CVD in people with diabetes 2-4 times
more likely than in those without diabetes

Upp to 12% of CVD deaths in the Asia-Pacific

region due to diabetes

India – more than 150,000 CVD deaths due

to diabetes

China – 70,000 CVD deaths from diabetes

 Natural History
y of Type
yp 2 Diabetes
Age 0-15+ 15-40+ 15-60+ 25-70+
Genetic
b k
background
d for:
f
– Insulin sensitivity Microvascular
– Insulin secretion complications
– Complications

Environmental
factors: Disability
– Nutrition
– Obesity
– Physical inactivity
Postprandial Fasting
IGT
hyperglycemia hyperglycemia
D th
Death

– Insulin resistance – Pseudo-normal – Hypoinsulinemia

– Hyperinsulinemia insulin – Blindness
– ↓ HDL cholesterol – Retinopathy – Renal failure
– ↑ Triglycerides – Nephropathy – Amputation
– Hypertension – Neuropathy – IHD
– Accelerated – Stroke
atherosclerosis
Disability
Macrovascular complications
Manifestsi klinik pre
pre-diabetes
diabetes

1. Impaired fasting glucose ( IFG )

GD puasa : 100 mg/dl – 125 mg/dl

2. Impaired glucose tolerance ( IGT )

GD 2 jam PP 140 – 199 mg/dl ( OGTT )

 Abnormalities of the CV system
y specific
p to
diabetes

Microangiopathy Autonomic Neuropathy Other Blood

Vessel Damage

What is it? Damage to small blood Damage to nerve supply of Damage to inner/outer lining of
vessels and capillary internal organs blood vessels
circulation

Clinical – Retinopathy – Problems with pulse rate – Impaired regularity of

Outcome – Nephropathy – Postural fall in BP blood flow
– Neuropathy – Foot ulcers – Weakened vessel walls
– Diabetic foot – Impotence – Aggravated microangiopathy
– Gastrointestinal dysfunction – Atherosclerosis/
macroangiopathy

International Diabetes Federation, 2006.

Does improved glycemic control
reduce CVD risk?
• Improved glycemic control can prevent
onset or progression of microvascular
complications
• BUT:
– We need d to
t aggressively
i l treat
t t allll off the
th
commonly associated features of
diabetes in order to effectively reduce
patient CVD risk

Marks J. Clin Diab 2003;21:99-100.

Lowering HbA1C Reduces
Risk
s oof Complications
Co p ca o s
In intensively treated patients, HbA1C was 7.0% compared with 7.9% in
conventionally treated patients. This 0.9% decrease in HbA1C is
associated with a reduction in risk for diabetic complications.

MI
-16 Borderline significance
Retinopathy
-21 Significant
Cataract extraction
-24 Borderline significance
Microvascular endpoint
-25 Significant
Albuminuria at 12 years
-34 Significant
Any diabetes-related
-12 Significant endpoint
0 -10 -20 -30 -40
50
-50

UK Prospective Diabetes Study (UKPDS) Group (33). Lancet 1998;352:837-53.

Recommendations for glycemic, blood pressure,
and lipid control for adults with diabetes

A1C <7.0%
Blood pressure 130/80 mmHg
Lipids
<100 mg/dL (2.6 mmol/L)*
– LDL-C

* In patients with overt CVD

CVD, treatment with a statin to lower LDL
LDL-C
C to <70
mg/dL (<1.8 mmol/L) is an option.

American Diabetes Association. Diabetes Care 2008;31(1):S12-S54.

 2. Complications of Hypertension
in Patients with Diabetes

Microvascular Macrovascular
R
Renal
l di
disease C di di
Cardiac disease

Autonomic neuropathy Cerebrovascular disease

Eye disease (glaucoma, Reduced survival and

retinopathy with potential recovery rates from stroke
blindness)
Peripheral vascular disease
UKPDS Blood Pressure Study:
Tight
g vs. Less Tight
g Control
• 1148 Type 2 patients
– Intensive BP group: 144/82 mmHg
– Controls: 154/87 mmHg

Endpoint Risk Reduction (%) p-value

Any diabetes-related 24 0.0046
endpoint
Diabetes-related 32 0.019
deaths
Heart failure 56 0.0043
Stroke 44 0.013
Myocardial infarction 21 NS
Microvascular disease 37 0.0092

UK Prospective Diabetes Study Group. BMJ 1998;317:703-13.

3. Overweight and Obesity
Based on BMI,
BMI Waist Circumference (WC)
(WC),
and Associated Disease Risk*

BMI Obesity Disease Risk*

(kg/m2) Class (Relative to Normal
Weight and WC)
Men <40 in (<102 cm) >40 in ( >102 cm)
Women <35 in (<88 cm) >35 in ( >88 cm)

Underweight <18.5 - -
Normal** 18.5-24.9 - -
Overweight 25.0-29.9 Increased High
Obesity 30.0-34.0 I High Very high
35.0-39.9 II Very high Very high
Extreme obesity >40 III Extremely high Extremely high

* Disease risk for type 2 diabetes, hypertension, and CVD

** Increased WC can also be a marker for increased risk, even in people of normal weight

NHLBI Obesity Education Initiative, 2000.

 Risiko kematian berdasarkan
Index Masa Tubuh ( IMT )
3.0
Men
2.6
of Death

Women
2.2
Relatiive Risk o

1.8

1.4

1.0
Lean Overweight
g Obese
0.6
<18.5 18.5 20.5 22.0 23.5 25.0 26.5 28.0 30.0 32.0 35.0 >40.0
– – – – – – – – – –
20.4 21.9 23.4 24.9 26.4 27.9 29.9 31.9 34.9 39.9
Body Mass index
The Obesity Society, 2008.
Calle EE et al. N Engl J Med 1999;341:1097-105.
Abdominal Obesity and
Increased Risk of CHD
Waist circumference independently associated with increased age-adjusted
risk of CHD,, even after adjusting
j g for BMI and other CV risk factors

3.0
2.44
25
2.5 p for trend = 0.007 2.31
2.06
e Risk

2.0
Relative

15
1.5 1.27
1.0

05
0.5

0.0
<69.8 69.8-<74.2 74.2-<79.2 79.2-<86.3 86.3-<139.7

Quintiles of Waist Circumference (cm)

CVD Risk Associated with WC
e in Normal
Even o a Weight
e g Individuals
d dua s
n=69,409 men p<0.01 for all

20 21%
1%
3%
ency (%)

15 13%

21%
10 6%
Freque

1% ≥30
9%
5 26%
≥25 - 30

0 <25
<90 ≥90 - <101 ≥101
Waist Circumference Tertile (cm)

Balkau B et al. Circulation 2007;116(17):1942-51.

Multiple Factors Associated with
Obesityy Give Rise to Increased Risk of CVD
Primary Intermediate
metabolic vascular disease Intravascular Clinical
disturbance risk factor pathology event

Insulin
resistance

Hypertension

Dyslipidemia

Atherosclerosis
Hyperglycemia
• Coronary arteries
• Carotid arteries
Overnutrition Hyperinsulinemia •
•
Cerebral arteries
Aorta
CVD
• Peripheral arteries
Inflammation
Hypercoagulability
Impaired
fibrinolysis
Endothelial
dysfunction
Metabolic/Vascular Benefits
off 10% W
Weight
i ht L
Loss
• In diabetes:
– Up to 50% ↓ in fasting glucose for newly
diagnosed type 2 patient

• At risk
i k ffor di
diabetes:
b t
>30% ↓ in fasting insulin
>30%  in insulin sensitivity

• Mortality:
>20% ↓ all-cause mortality
>30% ↓ in diabetes-related deaths
>40% ↓ in obesity-related deaths

Haslam D et al. BMJ 2006;333:640-2.

Impact of Weight Loss on Risk Factors
~5% 5%-10%
Weight
g Loss Weight
g Loss
HbA1c ↓ 1 ↓ 1

Bl d pressure
Blood ↓ 2 ↓ 2

Total cholesterol ↓ 3 ↓ 3

HDL cholesterol ↑ 3 ↑ 3

Ti l
Triglycerides
id ↓ 4

The Obesity Society, 2008.

Wing RR et al.
al Arch Intern Med 1987;147:1749-53.
1987;147:1749 53
Mertens IL, Van Gaal LF. Obes Res 2000;8:270-8.
Blackburn G. Obes Res 1995;3(Suppl 2):211S-16S.
Ditschunheit HH et al. Eur J Clin Nutr 2002;56:264-70.
 4 Dislipidemia
4.
• Kolesterol total,
total LDL
LDL, HDL rendah ,
ipertrigliseridemia
• Prediktor CVD
• 25 % penduduk US
• Penurunan 10 % kolesterlol total dapat
menurunkan risiko CVD 30 %
Risk of CHD by Triglyceride Level:
The Framingham Heart Study
3

M
Men W
Women
2.5
n=5127
Relative Risk

1.5

0.5

0
50 100 150 200 250 300 350 400
(0.6) (1.1) (1.7) (2.3) (2.8) (3.4) (4.0) (4.5)
Faktor risiko dislipidemia

•Rokok
•Tekanan darah tinggi
•HDL rendah ( < 40 mg/dl )
•Riwayat keluarga
i ( pria
•Usia i ≥ 45
4 tahun
h wanitai ≥ 55 tahun
h )
 5 Insulin Resisten
5.
• Gangguan kemampuan insulin untuk
menstimulasi penggunaan glukosa di jaringan
perifer dan menekan produksi glukosa hati.

Dipengaruhi
p g oleh :
1. berat badan berlebih 4. aktivitas fisik
2.. Umur
U u 5. pengobatan
pe goba a
3. genetik 6. puber/kehamilan
 Efek Resistensi Insulin

Glucose uptake
p ↓
Glucose oxidation ↓

Insulin Hyperinsulinemia
Lipolysis ↑
Hyperglycemia
resistance
i t F fatty
Free id ↑
f tt acid
Dyslipidemia

Glucose uptake ↓
production ↑
Glucose p
VLDL synthesis ↑ Cardiovascular
disease
Insulin Resistance and PAD

9
8
PAD Prevalencce (%)

7
p trend = 0.037
6
5

4
3

2
1
Q1 Q2 Q3 Q4
<1.08 1.08-1.86 1.86-3.34 >3.34

HOMA IR Quartiles
HOMA-IR Q til

Pande RL et al. Circulation 2008;118:33-41.

 6 Inflamasi
6.
• Peningkatan reaksi inflamasi akibat
injuri
• Mayor komponen dari atherosklerosis
• Marker : C Ractive Protein
• Protrombic state
• Risiko CVD 1,5
, – 4 kali
 Faktor risiko inflamasi
1. Merokok
1
2. Obesitas
3 Dislipidemia
3. Di li id i
4. Hipertensi
5. Diabetes

Pencegahan : aspirin
 Kesimpulan
• Penyakit
y jjantung
gppembuluh darah mempunyai
p y risiko
mortalitas CVD yang sama diabetes Melitus
• Faktor risiko kardiometabolik merupakan faktor
risiko
i ik bbersama tterhadap
h d ti
timbulnya
b l penyakit
kit
jantung dan diabetes

• Penyakit jantung dan diabetes akan menghadapi

hal sama thd mortalitas
• Intervensi faktor risiko kardiometabolik dapat
mengurangi resiko kejadian diabetes dan CVD
dengan berbagai komplikasinya