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Curriculum vitaeCurriculum vitae• Nama : Em YunirNama : Em Yunir• Tempat/tanggal lahir : Jakarta/ 9 Juni 1962• Agama : Islam• Lulus Fakultas kedokteran Universitas Indonesia tahun 1988Lulus 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 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 DARAHPENYAKIT JANTUNG DAN PEMBULUH DARAH
EM YUNIREM YUNIRDIVISI METABOLIK DAN ENDOKRIN
FKUI/RSUPN CIPTOMANGUNKUSUMO FKUI/RSUPN CIPTOMANGUNKUSUMO
Penyakit Jantung Pembuluh DarahPenyakit Jantung Pembuluh DarahPenyakit Jantung Pembuluh DarahPenyakit Jantung Pembuluh Darah
ddJantung danpembuluh
Jantung danpembuluh Stroke Stroke
darah jantungdarah jantung
PADPAD
Penyakit jantung pembuluhdarah mempunyai risikodarah mempunyai risiko
kematian yang sama besard di b t litdengan diabetes melitus
7-Year Incidence of Fatal/Nonfatal MI
From the East-West Study
e of (%
)
Diabetic (n=1059)Nondiabetic (n=1373)
40
5045
45†
ence
Rat
enf
arct
ion
20
3025
35
18 8* 20.2
ear I
ncid
eoc
ardi
al In
10
20
5
15
3.5
18.8
7-ye
Myo 0
No DM, no MI No DM, MI DM, no MI DM, MI
5
* 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 hdarah
Penyebab utama kematian di USPenyebab utama kematian di US
Penyebab 40 % angka kematian CVDy % g
1/3 diantaranya kematian premature
Suddent death usia 15-34 tahun
Angka kecacatan >>
CDCP 2007
Diabetes Melitus Diabetes Melitus
Meningkatkan risiko kematianMeningkatkan risiko kematianMeningkatkan risiko kematianMeningkatkan risiko kematian
Meningkatkan angka kesakitanMeningkatkan angka kesakitanMeningkatkan angka kesakitanMeningkatkan angka kesakitan
Komplikasi kronisKomplikasi kronispp
KecacatanKecacatan
Penurunan kwalitas hidupPenurunan kwalitas hidup
ADA 2008
Cardiometabolic RiskCardiometabolic Risk
Sekelompok faktor risiko terhadapl kit j t dmunculnya penyakit jantung dan
diabetes tipe 2 di kemudian hari
Beberapa faktor risiko dapatdimodifikasi untuk pencegahan
Faktor-faktor risiko kardiometabolik Faktor faktor risiko kardiometabolik
Dapat dimodifikasi Tidak dapat dimodifikasip p• Berat badan lebih/obesitas •Umur
• Gula darah diatas normal •Etnis/suku bangsa• Gula darah diatas normal •Etnis/suku bangsa• Dislipidemia :kolesterol LDL ,
HDL , Trigliserida•Jenis kelamin
• Tekanan darah tinggi •Keturunan• Hiperkoagulasi• InflamasiInflamasi• Merokok• Kurang aktivitas• Pola makan tidak sehat
Overweight / ObesityGeneticsAge
Abnormal lipid metabolismInsulin resistance syndrome
Insulin Resistance
•LDL ↑•Apo-B ↑•HDL-C ↓
?
su es sta ce sy d o e
↑Glucose↑
Lipids ↑BP•TG ↑
Cardiometabolic risk Age race
p
Cardiometabolic riskGlobal diabetes / CVD risk
Age, race, sex,
family history
Inflammation Smoking
Physical activity Inflammation Hypercoagulatio
nElevated blood pressure
Physical activity
Brunzell JD et al. Lipoprotein Management in Patients with Cardiometabolic Risk. J Am Coll Cardiol
2008;51:1512-24.
1. Diabetes
Risk of CVD in people with diabetes 2-4 times more likely than in those without diabetes more likely than in those without diabetes
Up to 12% of CVD deaths in the Asia-Pacific pregion due to diabetes
India – more than 150,000 CVD deaths due to diabetes
China – 70,000 CVD deaths from diabetes
Natural History of Type 2 Diabetesy yp
Genetic b k d f
Age0-15+ 15-40+ 15-60+ 25-70+
background for:– Insulin sensitivity– Insulin secretion– Complications
Environmental
Microvascular complications
Environmental factors:
– Nutrition– Obesity– Physical inactivity
Postprandial Fasting D th
Disability
– Insulin resistance
IGT Postprandial hyperglycemia
Fasting hyperglycemia Death
– Pseudo-normal – Hypoinsulinemia– Hyperinsulinemia– ↓ HDL cholesterol– ↑ Triglycerides– Hypertension– Accelerated
insulin– Retinopathy– Nephropathy– Neuropathy
– Blindness– Renal failure– Amputation– IHD– StrokeAccelerated
atherosclerosisStroke
Macrovascular complicationsDisability
Manifestsi klinik pre-diabetes Manifestsi klinik pre diabetes
1. Impaired fasting glucose ( IFG )1. Impaired fasting glucose ( IFG )
GD puasa : 100 mg/dl – 125 mg/dlGD puasa : 100 mg/dl – 125 mg/dl
2. Impaired glucose tolerance ( IGT )2. Impaired glucose tolerance ( IGT )
GD 2 jam PP 140 – 199 mg/dl ( OGTT ) GD 2 jam PP 140 – 199 mg/dl ( OGTT )
Abnormalities of the CV system specific to y pdiabetes
Microangiopathy Autonomic Neuropathy Other Blood Vessel Damage
What is it? Damage to small blood vessels and capillary circulation
Damage to nerve supply of internal organs
Damage to inner/outer lining of blood vessels
Clinical Outcome
– Retinopathy– Nephropathy– Neuropathy
– Problems with pulse rate– Postural fall in BP– Foot ulcers
– Impaired regularity of blood flow
– Weakened vessel walls– Diabetic foot – Impotence
– Gastrointestinal dysfunction– Aggravated microangiopathy– 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: d t i l t t ll f th – We need to aggressively treat all of the
commonly associated features of diabetes in order to effectively reduce diabetes in order to effectively reduce patient CVD risk
Marks J. Clin Diab 2003;21:99-100.
Lowering HbA1C Reduces Risk of Complicationss o Co p ca o sIn 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.
MIBorderline significance-16Retinopathy
Cataract extractionBorderline significance
Significant-21
-24Microvascular endpoint
Albuminuria at 12 yearsSignificant
Significant
-25
-34Any diabetes-related
endpointSignificant-120 -10 -20 -30 -40
-50
UK Prospective Diabetes Study (UKPDS) Group (33). Lancet 1998;352:837-53.
50
Recommendations for glycemic, blood pressure, and lipid control for adults with diabetes
A1C <7.0%Blood pressure 130/80 mmHgLipids
– LDL-C <100 mg/dL (2.6 mmol/L)*
* In patients with overt CVD treatment with a statin to lower LDL C to <70 In patients with overt CVD, treatment with a statin to lower LDL-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 Diabetesin Patients with Diabetes
Microvascular MacrovascularR l di C di diRenal disease Cardiac disease
Autonomic neuropathy Cerebrovascular disease
Eye disease (glaucoma, retinopathy with potential
Reduced survival and recovery rates from stroke
blindness)Peripheral vascular disease
UKPDS Blood Pressure Study:Tight vs. Less Tight Controlg g• 1148 Type 2 patients
– Intensive BP group: 144/82 mmHgIntensive BP group: 144/82 mmHg – Controls: 154/87 mmHg
Endpoint Risk Reduction (%) p-valueAny diabetes-related endpoint
24 0.0046
Diabetes-related deaths
32 0.019
Heart failure 56 0.0043
Stroke 44 0.013
Myocardial infarction 21 NS
UK Prospective Diabetes Study Group. BMJ 1998;317:703-13.
Microvascular disease 37 0.0092
3. Overweight and Obesity Based on BMI Waist Circumference (WC)Based on BMI, Waist Circumference (WC), and Associated Disease Risk*
BMI (kg/m2)
Obesity Class
Disease Risk*(Relative to Normal
Weight and WC)Weight and WC)Men <40 in (<102 cm) >40 in ( >102 cm)Women <35 in (<88 cm) >35 in ( >88 cm)
UnderweightNormal**OverweightObesity
<18.518.5-24.925.0-29.930.0-34.0 I
--
IncreasedHigh
--
HighVery high
Extreme obesity35.0-39.9
>40IIIII
Very highExtremely high
Very highExtremely 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 )
Men3.0
Index Masa Tubuh ( IMT )of
Dea
th
Men
Women2.2
2.6
ive
Ris
k o
1.4
1.8
Rel
ati
Lean Overweight Obese1.0
1.4
<18.5 18.5–
20.4
20.5–
21.9
22.0–
23.4
23.5–
24.9
25.0–
26.4
26.5–
27.9
28.0–
29.9
30.0–
31.9
32.0–
34.9
35.0–
39.9
>40.0
g0.6
Body Mass indexThe Obesity Society, 2008.
Calle EE et al. N Engl J Med 1999;341:1097-105.
Abdominal Obesity and Increased Risk of CHDIncreased Risk of CHD
Waist circumference independently associated with increased age-adjusted risk of CHD, even after adjusting for BMI and other CV risk factors , j g
2 5
3.02.44
1 5
2.0
2.52.06
2.31 2.44p for trend = 0.007
e R
isk
0 5
1.0
1.5 1.27
Rel
ativ
e
0.0
0.5
<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 Even in Normal Weight Individualse o a e g d dua s
n=69,409 men p<0.01 for all
201%
21%
10
15
ency
(%)
13%
21%6%
1%3%
5
10
≥25 - 30
≥30
Freq
ue
26%9%
1%
0<90 ≥90 - <101 ≥101
<25
Waist Circumference Tertile (cm)
Balkau B et al. Circulation 2007;116(17):1942-51.
Multiple Factors Associated with Obesity Give Rise to Increased Risk of CVD
Primarymetabolic
disturbance
Intermediate vascular disease
risk factor Intravascular
pathologyClinicalevent
y
Hypertension
Insulin resistance
Dyslipidemia
Hyperglycemia Atherosclerosis
Overnutrition Hyperinsulinemia
Hyperglycemia• Coronary arteries• Carotid arteries• Cerebral arteries• Aorta• Peripheral arteries
CVDInflammation
Impairedfibrinolysis
Hypercoagulability
• Peripheral arteries
Endothelial dysfunction
Metabolic/Vascular Benefits f 10% W i ht L
• In diabetes:
of 10% Weight Loss
– Up to 50% ↓ in fasting glucose for newly diagnosed type 2 patient
At i k f di b t• At risk for diabetes:>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%Weight Loss
5%-10%Weight Lossg g
HbA1c ↓ ↓
Bl d ↓1
2
1
2↓Blood pressure ↓
Total cholesterol
2
3
2
3↓
↓
↓
HDL cholesterol
T i l id
33 3
4↓↑ ↑
Triglycerides
The Obesity Society, 2008.Wing RR et al Arch Intern Med 1987;147:1749 53
4↓
Wing RR et al. Arch Intern Med 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. Dislipidemia
• Kolesterol total LDL HDL rendah Kolesterol total, LDL, HDL rendah , ipertrigliseridemia
• Prediktor CVD• 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 W
Ris
k
n=5127
2
2.5Men Women
Rel
ativ
e
1
1.5
0.5
1
050
(0.6)100(1.1)
150(1.7)
200(2.3)
250(2.8)
300(3.4)
350(4.0)
400(4.5)
Faktor risiko dislipidemiaFaktor risiko dislipidemia
•Rokok•Tekanan darah tinggi•HDL rendah ( < 40 mg/dl )•Riwayat keluarga
i ( i ≥ 4 h i ≥ h )•Usia ( pria ≥ 45 tahun wanita ≥ 55 tahun )
5 Insulin Resisten 5. Insulin Resisten • Gangguan kemampuan insulin untuk Gangguan kemampuan insulin untuk
menstimulasi penggunaan glukosa di jaringan perifer dan menekan produksi glukosa hati.
Dipengaruhi oleh :p g1. berat badan berlebih 4. aktivitas fisik2. Umur 5. pengobatan. U u 5. pe goba a3. genetik 6. puber/kehamilan
Efek Resistensi Insulin
Glucose uptake ↓pGlucose oxidation ↓
Insulin i t
Lipolysis ↑F f tt id ↑
HyperinsulinemiaHyperglycemiaresistance Free fatty acid ↑ HyperglycemiaDyslipidemia
Glucose uptake ↓Glucose production ↑p
VLDL synthesis ↑ Cardiovascular disease
Insulin Resistance and PAD
9
p trend = 0.037
6
7
8
ce (%
)
4
5
6
Pre
vale
nc
1
2
3
PAD
1 Q1<1.08
Q21.08-1.86
Q31.86-3.34
Q4>3.34
HOMA IR Q til
Pande RL et al. Circulation 2008;118:33-41.
HOMA-IR Quartiles
6 Inflamasi6. Inflamasi
• Peningkatan reaksi inflamasi akibat Peningkatan reaksi inflamasi akibat injuri
• Mayor komponen dari atherosklerosis• Mayor komponen dari atherosklerosis• Marker : C Ractive Protein• Protrombic state• Risiko CVD 1,5 – 4 kali ,
Faktor risiko inflamasi Faktor risiko inflamasi
1 Merokok1. Merokok2. Obesitas
3 Di li id i3. Dislipidemia4. Hipertensi5. Diabetes
Pencegahan : aspirin
Kesimpulan Kesimpulan • Penyakit jantung pembuluh darah mempunyai risiko y j g p p y
mortalitas CVD yang sama diabetes Melitus• Faktor risiko kardiometabolik merupakan faktor
i ik b t h d ti b l kit risiko bersama terhadap timbulnya penyakit 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 dengan berbagai komplikasinya