3

Estimated Direct Estimated Indirect Costs

Medical Costs (disability, work loss,
premature mortality)

Cardiovascular
Disease $296 billion $152 billion

Diabetes $116 billion $58 billion

TOTAL $412 billion $210 billion

*Note: these figures may not account for potential overlap.

Sources: 2008 statistics from the American Diabetes Association and American Heart Association.
  Desirable — Less than 200 mg/dL
 Borderline high risk — 200–239 mg/dL
 High risk — 240 mg/dL and over

American Diabetes Association. Understanding Cardiometabolic Risk: Broadening Risk Assessment and
Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center
 Overweight / Obesity
Age Genetics Abnormal Lipid
Metabolism
Insulin Resistance LDL 
Insulin Resistance ? ApoB 
Syndrome HDL 
 Lipids BP Glucose Trigly. 

Cardiometabolic Risk
Age, Race,
Global Diabetes / CVD Risk
Gender,
Family History

Smoking
Inflammation
Physical Inactivity
Hypercoagulation
Unhealthy Eating
Hypertension
 Increased: Decreased:

 Triglycerides  HDL
 VLDL  Apo A-I
 LDL and small
dense LDL
 ApoB

American Diabetes Association. Diabetes Care. 2007;30:S4-41.

 Modifiable
 Age  Overweight

 Race/ethnicity
 Abnormal lipid metabolism
 Inflammation,
 Gender hypercoagulation
 Family history  Hypertension
 Smoking
 Physical inactivity
 Unhealthy diet
 Insulin resistance
 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

Despres JP, et al. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881-887.
 Men Women
300
267
250
200
200
Incidence of
CVD 150 125 121 128
per 1,000 105
100

50

0
<100 110-129 130+ <110 110-129 130+
n=56 n=75 n=30 n=191 n=199 n=78
*Metropolitan Relative Weight percent
(percentage of desirable weight)
Hubert HB et al. Circulation. 1983;67:968-977
LDL CHOLETEROL
< 100 Normal
100 – 129 Normal tinggi
130 – 159 Borderline tinggi
160 – 180 Tinggi
≥ Sangat tingggi
HDL CHOLESTEROL
< 40 Rendah
≥ 60 Tinggi

CHOLESTEROL
< 200 Diinginkan
200 – 239 Borderline tinggi
≥ 240 Tinggi
Ischemic Heart Disease

Acute Coronary Syndrome

Rheumatic Heart Disease

Ischemic Heart Disease

Cerebrovascular Disease (Stroke)

Peripheral Vascular Disease

ATEROSKLEROSIS

Disease have the character of dynamic &

progressive coming from combination of
endothelial dysfunction & inflammation

Playing a part important at :

Initiation
Progressing
Destabilizes of plaque atherosclerosis
 ATHEROSCLEROSIS TIMELINE

Foam Fatty Intermediate Fibrous Complicated

Cells Streak Lesion Atheroma Plaque Lesion/Rupture

Endothelial Dysfunction
From first decade From third decade From fourth decade
Smooth muscle Thrombosis,
Growth mainly by lipid accumulation & collagen hematoma

Adapted from Stary HC et al. Circulation 1995;92:1355-1374

INITIATION & INFLAMMATION STAGE
in Atherosclerosis Lesion
MACROPHAGE ACCUMULATION
& FOAM CELLS FORMATION
ATHEROSCLEROSIS LESION
ADVANCED
 FAKTOR-FAKTOR RISIKO PJK

F. Risiko Mayor (Utama) F. Risiko Minor

Dislipidemia Hiperurikemi
Hipertensi Obesitas
Merokok Aktivitas fisik <
Diabetes Melitus (DM) Stress
FAKTOR-FAKTOR RISIKO PJK
Faktor Risiko yg  dpt di modifikasi
Genetik
Ras / Etnik
Jenis Kelamin
Usia
Riwayat Keluarga Menderita PJK
Faktor Risiko yg dpt di modifikasi
Dislipidemia Obesitas
Hipertensi Aktivitas fisik <
Merokok Stress
Hiperurikemia
 CARDIOVASCULAR RISK
FACTORS
Enviromental & life-style risk factors
Smoking, bronchitis, obesity, Chlamydia,
alcohol, diet, social class, helicobacter, dental
infection, inflammation, bowel disease.

Endogenous risk factors

Lipids (triglyceride, cholesterol, apo A–I, apo B)
Clotting factors (fibrinogen, t-PA, FVII, FVIII, PAI)
White blood count, blood pressure
 FAKTOR RISIKO
INDEPENDEN & ADITIF :
Semakin banyak seseorang memiliki
Faktor Risiko semakin besar risikonya
utk menderita PJK
TDD :
Merokok
Kolesterol Total & LDL 
Kolesterol HDL
Hipertensi
DM
Usia lanjut
F. RISIKO PREDISPOSISI :
Memperbesar  Risiko PJK
Obesitas ( BMI > 25 mg/m2)
Obesitas Abdominal :
φ Pinggang > 94 cm ()
> 80 cm ()
Waist – Hip Ratio > 0.9 ()
> 0.8 ()
< Aktifitas fisik
Riwayat keluarga menderita PJK pada usia muda
( < 55 tahun utk  & < 65 tahun utk  )
Etnik tertentu
F. Psikososial
F. RISIKO KONDISIONAL :
 berhubungan dgn  risiko PJK

Tirgliserida 
Homosistein 
Lp (a) 
F. Protrombotik ( misal : Fibrinogen )
Penanda Inflamasi ( misal : CRP )
C ORONARY HEART DISEASE
RISK FACTORS

Small Dense LDL

Lipoprotein (a)
Homocysteine
Free radicals
Inflammation
Infection
immunology
Lp(a) :
Lp yg kaya kolesterol (LDL), dgn adanya apo(a) yg
terikat dgn apo B 100 melalui ikatan disulfida
F. Risiko independen PJK
Apo(a) homologi plasminogen
 Kompetisi dgn plasminogen Menggangu Fibrinolisis
yg  dpt diaktifkan o/ t-PA
Bekuan Fibrin  hancur
 Pembtkan plasminturbatasi Trombosis
Menangsang TGF-  Prokferasi sel otot polos
(tergantung plasmin)
Lp(a)  membentuk komplek dgn Ca pada lesi
aterosklerosis  pertumbuhan plak
HOMOSISTEIN
Senyawa antara yg terbentuk pd metabolisme
metionin
Kadarnya tergantung : – Genetik
Asupan asam folat, Vit. B6 & B12
Hiperhomosisteinemia  F. Risiko independen PJK

Homosistein :
Efek sitotoksik langsung  disfungsi endotel melalui
pembentukkan H2O2
 HO
 Oksidatif LDL
Mekan proferasi sel otot polos & merangsang
sintesis kolagen
Reference Value
Hcy level 5 – 15 mol/L
Hyperhomocysteinemia
Mild 15 – 30 mol/L
Moderate 30 – 100
Severe > 100
Primary prevention : Hcy < 14 mol/L
Secondary prevention : Hcy < 11 mol/L
(10/9 ?)
Endothelial dysfunction Impaired NO production
Production of ROS 
vWF + Thrombomodulin 
Tissue factor production 
AT III production 

Vascular smooth muscle cells Proliferation  ?

Foam cells formation 

LDL increased foam cells formationThiolation

Lipid peroxidation 
MI is usually diagnosed by a history
of :
 crashed chest pain (angina
pectoris) due to reduction of
coronary perfusion
 ECG changes characteristic of
an MI (fig) ;
 and the release of myocardial
enzymes are observed.
 Three enzymes are commonly
used in the diagnosis and follow-
up of the MI are:
 creatine kinase (CK)
 aspartate aminotransferase (AST)
 lactate dehydrogenase (LDH)
 CK is also released from
damaged skeletal muscle
(CK-MM). But its isoenzyme in
myocardial cells (CK-MB) is
more specific indicator,and its
increase is used in the
investigation of MI.
 CK–MB Enzyme activity by Photometric
method

 CK–MB Mass by Elisa method

 CK–MB Mass > CK–MB Activity
 AST and LDH releases are not
specific to cardiac muscle because :
 AST is also found in many acute
pathologies affecting the liver and
skeletal muscle
 LDH is also found in liver and red
cells
 Note that :
 in the first four hours after the
infarction the enzymes may
not be raised.

 the development of cardiac

arrhythmia is a major cause
of death in these patients.
 Two other tests are useful in MI：

 Myoglobin : it is detectable 1-3

hours after infarction. It may be
the earliest indicator in MI.
 Cytoplasmic protein
 Binds O2
 2% of muscle protein
 In skeletal & cardiac muscle
 Small size & soluble  rapidly excreted
to systemic circulation
 Reference range : < 116 ng/mL (97.5%)
 In IMA : Rises early as 2 hours
Peak within 4 – 9 hours
Clears rapidly within 24 hours
In IMA > 10X N
Helpful to rule in & rule out IMA as long
as other source could be ruled out
 Troponin I and T ( TnT, TnI)
They are highly sensitive and
specific markers for acute MI.
They are released from
damaged cardiac muscle cells
within 3-12 hours of the
infarction, but they remain
elevated for much longer (5-10
days and 2 weeks respectively).
Troponin T (TnT)
Troponin I (TnI)
Troponin C
 Relatively specific for cardiac damage
cTnT & cTnI

 Elevated in ACS patient with UA, non Q

wave IMA & Q wave IMA
 CK（MB） AST troponin LDH

Normal value 25-175 IU/L 5-40 IU/L <1.0 ng/mL 90-200 IU/L

Elevate time 3-6h 6-10h 4h 24-72h

peek 18h 12-48h 2-3d 3-4 d

Return normal 2-3 days 3-4 days 7-14 days 14days

 THE RELEASE KINETICS OF CARDIAC
TROPONIN I, CK-MB & MYOGLOBULIN
 Creatinin Kinase (CK) √
 Creatinin Kinase Myocard Band (CKMB) √
 Lactat Dehydrogenase (LDH) √
 Serum Glutamic Oxaloacetic Transaminase (SGOT) √
 Cardiac Troponin T (cTnT) √
 Cardiac Troponin I (cTnI) √
 Myoglobin √
 High Sensitivity C Reaktif Protein (hsCRP)
 N Terminal pro B type Natriuretic Peptide (NT pro-BNP)
 Brain Natriuretic Peptide (BNP)
 ACUTE MYOCARDIAL
INFARCTION

Definition :

Damage or death of an area of cardiac

muscle (myocardium) due to blockage
of blood supply to that area
 CLINICAL PRESENTATION

 Collapse
 Sudden death
 65% of all death from AMI occur in the
first 15 minutes
 Chest pain
 Central chest pain radiating to the left
arm & neck
 Breathlessness
 Acute cardiac failure
PENANDA JANTUNG PADA IMA

WaktuAwal WaktuPuncak Waktu

Marka Peningkatan Peningkatan Kembali
(jam) (jam) Normal
CK 4–8 12–24 72–96jam
CK-MB 4–8 12–24 48–72jam
Mioglobin 2–4 4–9 <24jam
LDH 10–12 48–72 7–10hari
TroponinI 4–6 12–24 3–10hari
TroponinT 4–6 12–48 7–10hari
Kyle C 2000
ACUTE MYOCARDIAL INFARCTION

Diagnosis (WHO, 1981) :

 Clinically
 ECG
 Laboratory
Find 2 of 3
For the first 24 hours after suspected IMA :
 Serial CK & CK-MB every 6 – 8 hours
(CK & CK-MB , CK-MB > 6%CK)
For the patient who comes > 2 days after
suspected IMA :
 LDH 
 LDH electrophoresis
(flipped LDH = LDH 1 > LDH 2)
ACUTE CORONARY SYNDROME

Symptoms of
Myocardial Ischemia

YES Acute MI
ST– segment elevation ?
(Q-wave, non Q-Wave)

Elevated serum YES

NSTEMI
biomarkers ?
NO
Unstable Angina
 CHALLENGE / WEAKNESS OF
WHO CRITERIA

CK & CK-MB :
 CK not cardiac specific

 CK-MB relatively cardiac specific,

but CK-MB is also found in
skeletal muscle
 DIAGNOSIS IS NECESSARY

 To confirm the presence of ACS (rule in) :

Early treatment

 To confirm the absence of ACS (rule out) :

To avoid unnecessary hospitalization
cost
REQUIRED LABORATORY TESTS

 Sensitive & specific

 Available
 Rapid result
 Low cost
 CK (Creatinin Kinase), CKMB (Creatinin
Kinase Miokard Band), LDH (Lactat
Dehydrogenase), cTn-T (Cardiac Troponin T),
cTn-I (Cardiac Troponin I), Mioglobin.

Petanda IMA & Non IMA

Hs CRP (High Sensivity C-reactive Protein), BNP (Brain

Natriuretic Peptide), Pro BNP (Pro-Brain Natriuretic Peptide),
Homocystein
2003 : AHA & CDC

hs – CRP & CVD

Primary Prevention
hs-CRP ~ CVD
Sudden Death
PAD
Secondary Prevention : (Prognostic)
hs-CRP ~ predict the occurrence of new
ACS in patient with UA & AMI
Measure hs-CRP twice
(optimally two weeks a part)
Establishing Baseline hs-CRP Levels

Measure hs-CRP twice, two weeks apart, in fasting or non

fasting metabolically stable patients. Average both results

If hs-CRP result > 10 mg/L

Repeat hs-CRP test in two weeks

If repeat hs-CRP result > 10 mg/L

Examine patient for infection or Non

cardiovascular etiology
(i.e. lupus, endocarditis, cancer, etc)
 HUBUNGAN CRP / hs-CRP dengan PKV / PJK
ATEROSKLEROSIS :

kadar terendah bukan sebab jantung

 plaque stabil
> plaque erosif
nyata  plaque ruptur
PKV STABIL :

hs-CRP tidak tergantung trombosis

INDIVIDU SEHAT / ASIMTOMATIK

korelasi kuat independent kadar CRP stabil PJK long –ter m

( RR = 2,0 ; confidence interval = 1,6- 2,5)
batas  risiko 1,5 – 4 x ;  sedang risiko 3- 6 x
Metoda yang sangat sensitif  mengukur
CRP dalam kuantitas yang kecil  Hs- CRP
 1. hs-CRP berkorelasi erat dengan risiko
kejadian PJK,kekambuhan & sudden
death.
2. hs-CRP secara konsisten meramalkan
kejadian koroner baru pada Unstable
angina dan IMA
-hs-CRP: sensitivitas analitik: 0,1 mg/L

- Kadar sebagai prediktor 1-5mg/L

- Prediktor terbaik dibanding faktor risiko lainnya pada

PJK spt Lp(a), LDLC,Homocystein, ratio TC/HDL

- Sebagai pemeriksaan skrining: - validasi yang baik

- tidak mahal
- widely available
Diharapkan pemeriksaan Hs-CRP sbg tes skrining dpt memotivasi:
modifikasi gaya hidup spt penurunan BB dan kontrol rutin DM

Penurunan CRP
Infeksi Chlamydia PneumonialF. Risiko PJK

Secara langsung menginfeksi sel vaskuler

Membangkitkan mekanisme pertahanan tubuh lokal
dalam ateroma (memperkuat respon terhadap
hiperkolesterolemia  sumber potensial utk
rangsangan inflamasi)
Studi epidemiologis : Pasien PJK  titer ab
chylamydia pneunomonial 
DNA Chlamydia pneumonial : di identifikasi pada
spesimen aterosklerotik manusia (teknik molekular)
Studi in vitro : C. pneumonial dpt menginfeksi &
bereplikasi di dlm sel otot polos, sel endotel &
makrofag (komponen-komponen penting dlm plak
aterosklerosis)
 Acute Coronary Syndrome

No ST elevation ST elevation

NSTEMI

Unstable Myocardial Infarction

Angina
NQMI Qw MI
CAUSATIVE AGENT :
 Streptococcus -hemolyticus
 Lancefield group A

EPIDEMIOLOGI :
 Children 5 – 15 years of age

 Infections  pharyngitis, skin infections

 3% of pharyngitis infection by streptococcus
a which are improperly treated  RF
 Streptococcus -hemolyticus
Lancefield Group A

Acute Infection (Pharyngitis or skin infection) :

 Acute Rheumatic Fever : 1 – 5 weeks
after
 Acute Giomerutonephritis: 10 days – 3
weeks after
Streptococcus -hemolyticus
Lancefield Group A
 PATOGENESIS (LANCEFIELD)

1. Direct infection by Streptococcus group A

2. Toxic effect of Streptococcal extracellular

products
3. Dysfunction or abnormal immune
response against extracellular or somatic
antigen produced by Streptococcus group
A
 RHEUMATIC HEART DISEASE

Jones Criteria (1944)

 Updated in 1992 by special writing group

of the American Heart Association
 Major
 Minor
 + Supporting data
RHEUMATIC HEART DISEASE

Jones Criteria (1992)

Major :
 Carditis (40 – 60%)
 Polyarthritis Migrans (75%)  Elbow,
wrist, ankle, knee
 Sydenham’s chorea (< 10%)
 Subcutaneous nodules
 Erythema marginatum (< 10%)
 RHEUMATIC HEART DISEASE

Jones Criteria (1992)

Minor :
 Clinicial (fever, arthralgia)

 ECG (lengthening of PR interval)

 Laboratory
 ESR , CRP , ASTO ,  Leuocyte 
RHEUMATIC HEART DISEASE

Jones Criteria (1992)

2 Major Criterias
OR
1 Major Criteria + 2 Minor Criterias
+
 RHEUMATIC HEART DISEASE

Jones Criteria (1992)

Supporting Data :
 Streptococcus group A Infection
 Throat swab culture (25 – 40%)
 Antigen test or ASO Titer increase (80%)
 Anti deoxyribonuclease B (anti DNAse B)
 Anti hyaluronidase (95%)
Chronic Heart Failure (CHF): The tip of the
ice berg = end stage
of heart disease
CHF
proBNP, TnT;
Digoxin, Digitoxin Myocardial
Injury
AMI
Troponin T, CK, CK-MB,
Myoglobin, LDH, AST(GOT) Thrombosis
Acute coronary syndrome Inflammation
Troponin T, hsCRP, Fibrinogen D-dimer,
AT III, Protein C, Protein S, APC-resistance
Antioxidative
Coronary heart disease Potential
Atherosclerosis Lipid
Cholesterol, LDL, HDL, Tg, Lp(a), Apo-A1, Apo-B, Glucose, HbA1c
Fructosamine, Insulin, Albumin, Homocysteine, Vitamin B12, Folate, hsCRP Status
Risk factors Diabetes
Family History, Age, Gender, Smoking, Physical Inactivity, Hypertension, Obesity,
Insulin Resistance, Diabetes, Thrombophilia, High Cholesterol, High Homocysteine,
Type 2
 Any abnormality
must be repeated
Fasting Plasma and confirmed on 2-hour Plasma
Glucose a separate day* Glucose On OGTT

Diabetes Mellitus Diabetes Mellitus

126 mg/dL 200 mg/dL
Impaired Fasting Impaired Glucose
Glucose Tolerance
100 mg/dL 140 mg/dL

Normal Normal

“Pre-Diabetes”

* One can also make the diagnosis of diabetes based on

unequivocal symptoms and a random glucose >200 mg/dL

Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care 2004; Supplement 1
  High-sensitivity CRP tests may be used to further
evaluate underlying risk

Relative risk categories

 Low risk <1 mg/L
 Average risk 1-3 mg/L
 High risk >3 mg/L

 Aspirin and statins reduce CRP levels

 Unclear whether CRP should be a treatment
target
 Reduce weight
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med.1999;340:115- 126. Ballantyne CH.
  Proinflammatory/prothrombotic
factors underlie cardiometabolic risk
 Inflammation is a major component of
atherogenesis and other
cardiometabolic problems
 Obesity is associated with
inflammation

Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115-126. Ballantyne CH, Nambi V. Markers
of inflammation and their clinical significance. Atherosclerosis suppl 2005; 6: 21-9. McLaughlin T et al. Differentiation
between obesity and insulin resistance in the association with C-reactive protein. Circulation. 2002;106:2908-2912.
 Total <200 mg/dL
LDL <70 mg/dL
HDL >40 men mg/dL
>50 women mg/dL
Triglycerides < 150 mg/dL

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults (Adult Treatment Panel III); National Cholesterol Education Program, National Heart, Lung,
and Blood Institute, National Institutes of Health. NIH Publication No. 01-3670, May 2001
 3
Men Women
2.5

2 n=5,127
Relative Risk

1.5

0.5

0
50 100 150 200 250 300 350 400
Triglyceride Level, mg/dL

Castelli WP. Epidemiology of triglycerides: a view from Framingham American Journal of Cardiology. 1992;70:3H-9H.
 Cigarette smoking
 Hypertension (≥140/90 mm Hg or
on antihypertensive medication)
 Low HDL-C (<40 mg/dL)
 Family history of early heart
disease
 Age (men ≥45 years; women ≥55
years)