Download - Cardiac Biomarker 2014
BIOMARKERS JANTUNG
Ima Arum L
History
MARKERS OF CARDIAC NECROSIS
What is Myocardial Infarction? Myocardial ischemia results from the reduction of coronary
blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue
When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs ---this is defined as:
myocardial infarction
Patogenesis Aterosklerosis
Biochemical Changes in Acute Myocardial Infarction(mechanism of release of myocardial markers)
ischemia to myocardial muscles (with low O2 supply)
anaerobic glycolysis
increased accumulation of Lactate
decrease in pH
activate lysosomal enzymes
disintegration of myocardial proteins
cell death & necrosis
release of intracellular contents to bloodBIOCHEMICAL
MARKERS
clinical manifestations (chest pain)
ECG changes
Diagnosis of Myocardial Infarction
SHOULD depend on THREE items
(as recommended by WHO)
1- Clinical Manifestations 2- ECG
3- Biochemical Markers
“Perfect” Cardiac Marker Early appearance
Accurate, specific, precise
Readily available, fast results
Cost-effective
Markers of Cardiac Necrosis
CREATIN KINASE (CK)
Enzim di berbagai jaringan, konsentrasi tinggi di otot untuk energi metabolisme.
Ada 2 subunit : B dan M isoform CK-MB, CK-BB, CK-MM
Konsentrasi CKMB tertinggi di sel otot jantung dan otot skelet
Dilepaskan dalam serum 48 jam setelah onsetKembali normal setelah 3 hari
CKMB Isoenzim CK
Meningkat 4 - 8 jam setelah infark puncak 12-24 jam kemudian
Persiapan sampel darah : - serum/ plasma heparin/ plasma EDTA - tidak boleh hemolisis - bila tidak langsung diperiksa serum disimpan beku - sampel stabil 24 jam pada suhu 40 C atau 1 jam pada suhu ruang
Cardiac Markers Release kinetics of cardiac markers in AMI
• Early, rapid, transient release of Myoglobin
• Delayed, sustained release of Troponin T
Compared with CK and CK-MB
25
20
15
10
5
01 3 5 7 10
days after onset of AMI
multiples of reference range
MyoglobinLDCK-MBTroponin ITroponin T
Figure of CPK, AST ( GOT ), and LD level after myocardial infarction (means of values for 200 patiens). Note that the CPK rise is earliest, the LD rise is latest, and the LD elevations are present longer than those of CPK and AST ( GOT ).
LDHEnzim mengkatalisis perubahan reversibel
laktat ke piruvat
Tersebar luas dalam macam2 jaringan peningkatan LDH sangat tidak spesifik
LDH meningkat pada kelainan sirkulasi (syok)
Ada 5 isoenzim LDH : LDH1-5Miokard dan eritrosit kaya LDH1
Miokardium mengandung lebih banyak LDH1 infark miokard rasio LDH1 : LDH2 >1
LDHSpesimen darah :
- Tidak boleh hemolisis ( eritrosit mengandung banyak LDH spesimen darah hemolisis ringan LDH meningkat )
- Segera dipisahkan jadi serum/ bekuan cegah pengeluaran LDH intrasel
- LDH dalam serum stabil 2 hari pada suhu 40 C - LDH rusak bila dibekukan
TROPONINMerupakan protein kontraktil di filamen serabut otot jantung Unit kontraktil otot skelet : filamen tipis dan tebal Troponin terdapat dalam filamen tipis , fungsi : mengontrol proses kontraksi
Kompleks Troponin terdiri dari 3 protein : - Troponin-C ( cTnC ) - Troponin-T ( cTnT ) - Troponin-I ( cTnI )
Kerusakan miokard troponin dilepas ke darah
Troponin T
TropomyosinActin
Troponin I
Troponin C
Head-to-Tail Overlap of Tropomyosin
• The Troponin complex: three unrelated proteins Troponin I, C and T which interact synergistically
• In the absence of Ca++, the Troponin complex and Tropomyosin inhibit myosin – actin interaction
• Troponin T in the myocardium is different from Troponin T in skeletal muscle
The Troponin complex
TROPONINHalf-life biologik dan kecepatan peningkatan kadar cTnT di serum sama dengan cTnI (2-4 jam).
Ukuran molekul cTnT lebih besar dari cTnI kadar cTnT di serum lebih lambat menjadi normal (14 hr)
Patogenesis pelepasan Troponin : kerusakan miokard (infark, miokarditis, kardiomiopati).
AMI kadar cTnI meningkat 2-8 jam onset
tergantung luas, letak infark, vaskularisasi koroner normal setelah 7 hr.
CARDIAC BIOMARKER
NATRIURETIC PEPTIDES
Natriuretic Peptides Present in two forms, atrial (ANP) and
brain (BNP) Both ANP and BNP have diuretic,
natriuretic and hypotensive effects Both inhibit the renin-angiotensin system
and renal sympathetic activity BNP is released from the cardiac
ventricles in response to volume expansion and wall stress
BNP Assay Approved by the FDA for diagnosis of
cardiac causes of dysnpea Currently measured via a rapid, bedside
immunofluorescence assay taking 10 minutes
Especially useful in ruling out heart failure as a cause of dyspnea given its excellent negative predictive value
BNP Came to market in 2000 based on data
from many studies, primarily the Breathing Not Properly (BNP) study
Prospective study of 1586 patients presenting to the ER with acute dyspnea
The predictive value of BNP much superior to previous standards including radiographic, clinical exam, or Framingham Criteria
BNP BNP has also shown utility as a
prognostic marker in acute coronary syndrome
It is associated with increased risk of death at 10 months as concentration at 40 hours post-infarct increased
Also associated with increased risk for new or recurrent MI
PROGNOSTIC MARKERS AND MARKERS OF RISK STRATIFICATION
Prognostic Markers and Markers of Risk Stratification
C-reactive protein Myeloperoxidase Homocysteine Glomerular filtration rate
C-Reactive Protein Multiple roles in cardiovascular disease
have been examined Screening for cardiovascular risk in
otherwise “healthy” men and women Predictive value of CRP levels for disease
severity in pre-existing CAD Prognostic value in ACS
C-Reactive Protein Pentameric structure consisting of five
23-kDa identical subunits Produced primarily in hepatocytes Plasma levels can increase rapidly to
1000x baseline levels in response to acute inflammation
“Positive acute phase reactant”
C-Reactive Protein Binds to multiple ligands, including many
found in bacterial cell walls
Once ligand-bound, CRP can: Activate the classical compliment pathway Stimulate phagocytosis Bind to immunoglobulin receptors
C-Reactive Protein:Risk Factor or Risk Marker? CRP previously known to be a marker of
high risk in cardiovascular disease More recent data may implicate CRP as
an actual mediator of atherogenesis Multiple hypotheses for the mechanism
of CRP-mediated atherogenesis: Endothelial dysfunction via ↑ NO synthesis ↑LDL deposition in plaque by CRP-
stimulated macrophages
CRP and CV Risk Elevated levels predictive of:
Long-term risk of first MI Ischemic stroke All-cause mortality
Myeloperoxidase Released by activated leukocytes at
elevated levels in vulnerable plaques Predicts cardiac risk independently of
other markers of inflammation May be useful in triage of ACS (levels
elevate in the 1st two hours) Also identifies patients at increased risk
of CV event in the 6 months following a negative troponin
NEJM 349: 1595-1604
Homocysteine Intermediary amino acid formed by the
conversion of methionine to cysteine Moderate hyperhomocysteinemia occurs
in 5-7% of the population Recognized as an independent risk
factor for the development of atherosclerotic vascular disease and venous thrombosis
Can result from genetic defects, drugs, vitamin deficiencies, or smoking
Homocysteine Homocysteine implicated directly in
vascular injury including: Intimal thickening Disruption of elastic lamina Smooth muscle hypertrophy Platelet aggregation
Vascular injury induced by leukocyte recruitment, foam cell formation, and inhibition of NO synthesis
Homocysteine Elevated levels appear to be an
independent risk factor, though less important than the classic CV risk factors
Screening recommended in patients with premature CV disease (or unexplained DVT) and absence of other risk factors
Treatment includes supplementation with folate, B6 and B12
Glomerular Filtration Rate The relationship between chronic kidney
disease and cardiovascular risk is longstanding
Is this the result of multiple comorbid conditions (such as diabetes and hypertension), or is there an independent relationship?
Glomerular Filtration Rate
Recent studies have sought to identify whether creatinine clearance itself is inversely related to increased cardiovascular risk, independent of comorbid conditions
Glomerular Filtration Rate Go, et al performed a cohort analysis of
1.12 million adults in California with CKD that were not yet dialysis-dependent
Their hypothesis was that GFR was an independent predictor of cardiovascular morbidity and mortality
They noted a strong independent association between the two
NEJM 351: 1296-1305
Glomerular Filtration Rate Reduced GFR has been associated with:
Increased inflammatory factors Abnormal lipoprotein levels Elevated plasma homocysteine Anemia Arterial stiffness Endothelial dysfunction
SELAMAT BELAJAR