Introduction to Cardiovascular Disease markers

Georgina Grimsey

Nov 22, 2019

Cardiovascular disease (CVD) is the group of anomalies that
involve the circulatory system (heart and/or blood vessels). Examples of CVD
are coronary artery diseases (such as angina and myocardial infarction, aka
heart attack), stroke, many heart-related ailments, venous thrombosis, and
peripheral artery disease. The underlying mechanism behind this myriad of
diseases remains elusive. Arteriosclerosis (hardening and loss of elasticity of the artery walls) and atherosclerosis
(build-up of fibrofatty plagues existing of cholesterol, triglycerides,
lymphocytes and minerals inside the artery walls) both negatively affect the
blood flow and may lead to stroke, or coronary or peripheral artery disease.

In clinical setting, CK-MB is an important serum marker for myocardial
infarction. D-dimer is used to diagnose pulmonary embolism and deep vein
thrombosis, while increased FABP3 levels may confirm or predict a heart attack.
MPO may be used as a prognostic marker for cardiovascular events, BNP indicates
left ventricular dysfunction,
and Myoglobin indicates muscular
damage. Both cTnI and cTnT are markers for myocardiac infarction, while ST2
provides prognostic information that is independent of other cardiac biomarkers.

Creatine Kinase (CK-MB)

The protein CK-M is a cytoplasmic enzyme involved in energy
homeostasis. This enzyme catalyses the transfer of phosphate between ATP and
various phosphagens such as creatine phosphate. It acts as a homodimer in
striated muscle as well as in other tissues, and as a heterodimer with a
similar brain isozyme CK-B (to become CK-MB) in heart. Elevation of CK in the
serum is an indication of damage to muscle. It therefore is indicative for
injury as result of anomalies like rhabdomyolysis, myocardial infarction,
muscular dystrophy, myositis, myocarditis, malignant hyperthermia and
neuroleptic malignant syndrome. Lowered CK can be indication of alcoholic liver
disease and rheumatoid arthritis.  

D-dimer (DD)

D-dimer is the degradation product of fibrin, created during
fibrinolysis when plasmin degrades the fibrin clot. As the fibrin clot is
assembled during thrombus formation, a rise in fibrin D-dimer levels is
indicative of thrombogenesis. The process of turnover of cross-linked fibrin
can therefore be assessed by the measurement of plasma D-dimer levels, which
are an indirect marker of intravascular fibrin formation. High levels have been
found in patients with overt thrombosis, pulmonary thrombo-embolism, and deep
venous thrombosis. However, increased extravascular fibrin turnover after major
injury or surgery, infection, inflammation, or malignancy can also activate
fibrinolysis and generate increased plasma fibrin D-dimer levels.

Fatty-Acid-Binding Protein 3 (FABP3)

The fatty-acid binding proteins (FABPs) are a family of
carrier proteins for fatty acids and other lipophilic substances. The FABP
specific for muscle and heart (FABP3 or H-FABP) is a low molecular weight
cytoplasmic protein released from myocardiocytes after an ischemic episode. H-FABP
is recommended to be measured together with Troponin to identify myocardial
infarction (MI) and acute coronary syndrome in patients presenting with chest
pain. H-FABP also has prognostic
value, as it has shown to predict MI up to one year in advance, and to predict
30-day mortality in acute pulmonary embolism.

Myeloperoxidase (MPO)

MPO is a peroxidase enzyme most abundantly expressed in
neutrophil granulocytes. It is a lysosomal protein released to carry out their
antimicrobial activity. MPO has a haem pigment, which causes its green colour
in secretions rich in neutrophils, such as pus and some forms of mucus.  MPO is a mediator of several inflammatory
cascades and higher serum levels have been associated with increased risk of
adverse cardiovascular events. Therefore, MPO and its downstream inflammatory
pathways represent attractive targets for prognostic and therapeutic
intervention of cardiovascular disease.

Myoglobin

Myoglobin is the oxygen carrier in the muscles in the same
way as haemoglobin is in the bloodstream. Myoglobin is only detected in the
blood after muscular injury. Hence, it is a sensitive marker for muscular
damage (rhabdomyolysis), but it is not specific enough on its own to act as a
diagnostic for acute myocardial infarction.

Brain natriuretic peptide (BNP)

BNP thanks its name by its discovery in pig’s brain.
However, in human its gene is mainly expressed in the heart’s ventricles (as
opposed to the Atrial Natriuretic Peptide). Both BNP and ANP act to reduce
sodium, and due to osmotic forces also water from the circulatory system, thus
reducing blood pressure. The prohormone proBNP (after removal of its signal peptide) is cleaved by a specific convertase into NT-proBNP
and the biologically active BNP-32, which are secreted into the blood in
equimolar amounts. The significantly longer half-life of NT-proBNP makes it a
preferred analyte over BNP-32 for diagnostic measurements. BNP and NT-proBNP
levels are typically increased in patients with left ventricular dysfunction,
but they are commonly used to rule our heart failure in an emergency setting,
and for screening and prognosis of heart failure.

Cardiac Troponin I (cTnI)

The muscle protein Troponin I is part of the troponin
protein complex involved in preventing actin to interact with myosin during
muscle relaxation. The gene TNNI3, encoding cardiac troponin I (cTnI), is
exclusively expressed in adult cardiac muscle.  This makes cTnI a highly specific diagnostic
marker for cardiac muscle injuries, and it has been universally used as
indicator for myocardial infarction. Increased levels of serum cTnI also
independently predict poor prognosis of critically ill patients in the absence
of acute coronary syndrome.

Cardiac troponin T (cTnT)

The muscle protein Troponin T is part of the troponin
protein complex involved in preventing actin to interact with myosin during
muscle relaxation. The gene TNNT2, encoding cardiac troponin T (cTnT), is
expressed in cardiac muscle and in embryonic skeletal muscle. Serum cardiac
troponin tests can be used to help diagnose several different heart disorders,
especially myocardial infarction.

ST2

Encoded by the IL1RL1 gene, the ST2 cardiac protein is a biomarker
of cardiac stress. ST2 signals the presence and severity of adverse cardiac
remodelling and tissue fibrosis, which occurs in response to myocardial
infarction, acute coronary syndrome, or worsening heart failure. ST2 provides
prognostic information that is independent of other cardiac biomarkers.

S100B is NOT a cardiovascular
biomarker, but a CNS biomarker.

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