Transcript Biomarkers in cardiac diseases

Szakács Júlia
M.D.
Department of Pathophysiology
Biomarkers in cardiac diseases
FAINELLI Manon
BOGÓ Ákos
Numbers…
 Cardiovascular diseases
 The most frequent cause of death
 7.5 millions of death/ year
 Important concerns in developed countries
Cardiac diseases
Ischemic diseases
Stable angina
Unstable angina
 Ischemic heart diseases:
hypoxia or anoxia as a
result of decrease or arrest
of oxygen delivery
 ACS: obstruction of
coronary arteries by a
thrombus
NSTEMI
Acute coronary
syndrome (ACS)
STEMI
Myocardial
infarction (MI)
Cardiovascular risk factors
 Age
 Genetics
 Smoking
 Arterial Hypertension
 Type II diabetes mellitus
 Inflammatory markers : CRP, endothelin…
 Protective factors:
 HDL-level
Atherosclerosis
 Progressive complex chronic inflammatory disease
 accumulation of
 oxidized LDL
 inflammatory cells
 calcifications and of fibrosis
 leading to plaque formation
 this set modifies the intima of large and medium artery vessels
Atherosclerosis
Essentials of Pathophysiology:
Concepts of Altered Health
State; C. MATTSON PORTH and
G.MATFIN
Myocardial infarction (MI)
 Acute myocardial ischemia leading to myocardial necrosis
 Diagnosis
 Cardiac biomarker levels
And at least of this items :
 Clinical symptoms of ischemia
 Modification of ST-segment
 Pathological Q waves
 Demonstration 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 procedures
European Heart Journal (2012) 33, 2551–2567
Clinical symptoms of MI
 chest pain (>20min)
 not affected by position changing),
 not relieved by nitroglycerine
 radiation of pain to the lower jaw or the left-arm, even gastric pain.
 Less specific symptoms:
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nausea or vomiting,
dyspnea,
asthenia
palpitations,
sweating
fainting
European Heart Journal (2012) 33, 2551–2567
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 pressure
 2 categories
 Heart failure with Preserved Ejection Fraction (HF-PEF)
 Heart Failure with Reduced Ejection Fraction (HF-REF)
 Different states
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Asymptomatic
Acute
Chronic
Compensated/Decompensated
Congestive
 Clinical classification: NYHA
European Heart Journal (2012) 33, 1787–1847
Clinical symptoms and signs
of HF
 Clinical symptoms
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Breathlessness
Orthopnea
Paroxysmal nocturnal dyspnea
Reduced exercise tolerance
Asthenia
 Signs
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Elevated jugular venous pressure
Hepatojugular reflux, hepatomegaly
Gallop rhythm (3rd heart sound)
Laterally displaced apical impulse
Cardiac murmur
Peripheral edema
Pulmonary crepitations
„Heart failure in a nutshell”
(From: rickolddoc.wordpress.com)
European Heart Journal (2012) 33, 1787–1847
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.
Inflammation
 CRP
 Peak and return to the base line are too late
 Correlation with MI
 can 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 = treatment
 Other inflammatory proteins
 IL-6 and TNF-α: asymptomatic HF screening
 PaPPA: risk of cardiovascular death and future MI
prediction
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 MI
 Uric acids indicates detrimental prognosis in HF
Neurohormones
Activation of
Sympathetic nervous system
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Renin-angiotensine-aldosterone
system
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Norepinephrin ↑
Components ↑
Predictors of mortality
Gerald W. Dorn II Circulation Research. 2011;108:1270-1283
Big Endothelin-1
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Elevated level post-MI
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Predictor of death and hospitalization
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CTproET1 is in use for measurement
Arginin Vasopressin
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Elevated level post-MI
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Persistently → heart failure / mortality
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For measurements: Copeptin
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(in combination with cTns)
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
Myocyte injury
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Severe cardiac disease impairs the heart
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Injury of cardiac muscle → release of
biomarkers
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Biomarkers reach the circulation with delays
http://slideplayer.com/slide/258211/
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
Choline
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Component of cell membrane (not specific)
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Ischemia, necrosis, ACS
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Predictor of cardiac arrest or death
H-FABP
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Cytosolic, low molecular weight protein
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Mainly expressed in myocardium
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Associated with MI, heart failure and death
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Combined with cTnI → higher sensitivity and NPV
Ischemia modified albumin (IMA)
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Most frequent plasma protein
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Ischemia → not able to bind divalent ion
albumin cobalt binding test
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Rapid elevation
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Contradictory results
Hs-Tn
High sensitivity troponin assays
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
Cardiac troponins (cTns)
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Complex of three regulatory proteins
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cTnI and cTnT is in use
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Specificity!
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Widest diagnostic window
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Preferred for MI detection and diagnosis
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Indicate poor prognosis
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The only biomarkers influencing the treatment
Creatine kinase (CK-MB)
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BM isotype – specific for myocardium
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Former „gold standard” in MI diagnostics
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Predictor of hospitalization and death
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Less sensitive /specific
Myoglobin
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Cytoplasmic heme protein
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Not specific!
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Earlier
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Early AMI detection (often in combination with cTns)
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
Myocyte stress
N-terminal pro-B-type natriuretic peptide (NT-proBNP)
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Inactive by-product of pro-BNP cleavage
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MI, heart failure and possibly ACS too
Others
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MR-proANP
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MR-proAdrenomedullin
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ST2 (plus IL-33)
Conclusion
 Nowadays, no perfect biomarker
 Need more studies
 Leads to a multimarker strategies
Thank you for your attention !