FAINELLI Manon BOGÓ Ákos Szakács Júlia MD Department of Pathophysiology Numbers Cardiovascular diseases The most frequent cause of death 75 millions of death year Important concerns in developed countries ID: 460526
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Slide1
Biomarkers in cardiac diseases
FAINELLI ManonBOGÓ Ákos
Szakács Júlia M.D. Department of PathophysiologySlide2
Numbers…
Cardiovascular diseases The most frequent cause of death 7.5 millions of death/ yearImportant concerns in developed countriesSlide3
Cardiac diseases
Ischemic heart diseases: hypoxia or anoxia as a result of decrease or arrest of oxygen deliveryACS: obstruction of coronary arteries by a thrombus
Ischemic diseases
Stable angina
Acute coronary syndrome (ACS)
NSTEMI
STEMI
Myocardial
infarction (MI)
Unstable anginaSlide4
Cardiovascular risk factors
AgeGeneticsSmokingArterial HypertensionType II diabetes mellitusInflammatory markers : CRP,
endothelin…Protective factors:HDL-level Slide5
Atherosclerosis
Progressive complex chronic inflammatory diseaseaccumulation ofoxidized LDL i
nflammatory cellscalcifications and of fibrosisleading to plaque formationthis set modifies the intima of large
and medium artery vesselsSlide6
Atherosclerosis
Essentials of Pathophysiology: Concepts of Altered Health
State; C. MATTSON PORTH and G.MATFINSlide7
Myocardial infarction (MI)
Acute myocardial ischemia leading to myocardial necrosisDiagnosisCardiac biomarker levelsAnd at least of this items :C
linical symptoms of ischemiaModification of ST-segmentPathological Q wavesDemonstration of loss cardiac muscle or function Thrombus into coronary artery
Clinical
classification
Type
1
: spontaneous MI due to ATS
Type 2
: secondary to an ischemic imbalance (e.g. coronary spasm, emboli, anemia)
Type 3
: sudden cardiac death when biomarkers value are not available with new ischemic ECG changes or new LBBB
Type 4 and 5: MI related to revascularization proceduresEuropean Heart Journal (2012) 33, 2551–2567
Slide8
Clinical symptoms of MI
chest pain (>20min) not affected by position changing),not relieved by
nitroglycerineradiation of pain to the lower jaw or the left-arm, even gastric pain. Less specific symptoms: nausea or vomiting,
dyspnea,asthenia palpitations,sweating
fainting
European Heart Journal (2012) 33, 2551–2567 Slide9
Heart failure
abnormality of the structure or the function of myocardium, which prevents enough oxygen delivery to satisfy the metabolic needs of the tissues, at a normal filling blood pressure2 categoriesHeart failure with Preserved Ejection
Fraction (HF-PEF)Heart Failure with Reduced Ejection Fraction (HF-REF)Different states AsymptomaticAcute
ChronicCompensated/DecompensatedCongestiveClinical classification: NYHA
European Heart Journal (2012) 33, 1787–1847 Slide10
Clinical symptoms and signs of HF
Clinical symptomsBreathlessnessOrthopneaParoxysmal nocturnal dyspneaReduced exercise tolerance
AstheniaSignsElevated jugular venous pressureHepatojugular reflux, hepatomegalyGallop rhythm (3rd heart sound)
Laterally displaced apical impulseCardiac murmurPeripheral edemaPulmonary crepitations
European Heart Journal (2012) 33, 1787–1847
„
Heart
failure
in
a
nutshell
”
(From: rickolddoc.wordpress.com)Slide11
BIOMARKERS
Definition:
-measurable and quantifiable biological parameter-suitable for early diagnosis, prognosis, follow-up and risk stratification-cardiospecific with
enough released concentration levels-easily measurable (
quick and adapted to
emergency
situations
)
-
accurate
-
reproducible-cost-effective
Chan D, Ng L.L. Biomarkers in acute myocardial infarction. BMC Med. 8:34 2010.Slide12
Inflammation
CRPPeak and return to the base line are too lateCorrelation with MIcan help to stratify, to screen ischemic heart disease and seems to be a prognostic factor of acute or chronic HF
But lack of specificity -> prentraxin-3 = treatmentOther inflammatory proteinsIL-6 and TNF-α: asymptomatic HF screening
PaPPA: risk of cardiovascular death and future MI predictionSlide13
Oxidative stress : indirect markers
Plasmaoxidized low density lipoproteins 8-isoprostane urinary levels correlate with matrix
metalloproteinases levels: predicting the risk of ventricular remodeling and more severe HF Myeloperoxidase: death caused by HF or MIUric acids indicates detrimental prognosis in HFSlide14
Neurohormones
Activation of S
ympathetic nervous systemNorepinephrin ↑Renin-angiotensine-aldosterone system
Components ↑Predictors of mortality
Gerald W. Dorn II Circulation Research. 2011;108:1270-1283Slide15
Big Endothelin-1
Elevated level post-MIPredictor of death and hospitalizationCTproET1 is in use for measurement
Arginin VasopressinElevated level post-MIPersistently → heart failure / mortality
For measurements: Copeptin(in combination with cTns
)Slide16
Biomarkers
Copeptin is
marked on this illustration post-MI
Kehl
DW,
Iqbal
N,
Fard
A,
Kipper
BA, De La
Parra
Landa A, Maisel AS. Biomarkers
in acute myocardial injury
. Translational Research. 159:252-64. 2012 Slide17
Myocyte injury
Severe cardiac disease
impairs the heartInjury of cardiac muscle
→ release of biomarkersBiomarkers reach
the
circulation
with
delays
http://slideplayer.com/slide/258211/Slide18
Biomarkers
Following
Tissue Ischemia
Kehl
DW,
Iqbal
N,
Fard
A,
Kipper
BA, De La
Parra
Landa
A, Maisel AS.
Biomarkers in acute myocardial injury. Translational Research. 159:252-64. 2012 Slide19
Choline
Component of cell membrane (not
specific)Ischemia, necrosis, ACSPredictor of
cardiac arrest or death
H-FABP
Cytosolic
,
low
molecular
weight
protein
Mainly expressed in myocardiumAssociated
with MI, heart failure and death
Combined with cTnI → higher sensitivity and NPVSlide20
Ischemia
modified albumin (IMA)Most frequent plasma
proteinIschemia → not able to
bind divalent ion albumin cobalt
binding
test
Rapid
elevation
Contradictory
results
Hs-Tn
High
sensitivity troponin assays Slide21
Biomarkers
Following
necrosis
Kehl
DW,
Iqbal
N,
Fard
A,
Kipper
BA, De La
Parra
Landa
A,
Maisel
AS.
Biomarkers
in acute myocardial injury. Translational Research. 159:252-64. 2012 Slide22
Cardiac troponins (
cTns)Complex of three regulatory proteinscTnI and cTnT
is in useSpecificity!Widest diagnostic windowPreferred for MI detection and diagnosis
Indicate poor prognosis The only biomarkers influencing the treatmentSlide23
Creatine
kinase (CK-MB)BM isotype – specific for myocardiumFormer „gold standard” in MI diagnostics
Predictor of hospitalization and deathLess sensitive /specificMyoglobin
Cytoplasmic heme proteinNot specific!
Earlier
Early
AMI
detection
(
often
in
combination
with cTns)Slide24
Biomarkers
Induced
by myocyte stretch
Kehl
DW,
Iqbal
N,
Fard
A,
Kipper
BA, De La
Parra
Landa
A,
Maisel AS. Biomarkers in acute myocardial injury. Translational
Research. 159:252-64. 2012 Slide25
Myocyte stress
N-terminal pro-B-type
natriuretic peptide (NT-proBNP)Inactive
by-product of pro-BNP cleavageMI, heart failure and possibly
ACS
too
Others
MR-proANP
MR-proAdrenomedullin
ST2 (plus IL-33)Slide26
Conclusion
Nowadays, no perfect biomarkerNeed more studiesLeads to a multimarker strategiesSlide27
Thank you for your attention !