Introduction to Cardiovascular Disease Markers

Kristina Whitfield

Nov 22, 2019

Science 2

Cardiovascular disease (CVD) is a group of anomalies that involve the circulatory system. As their underlying mechanism remains elusive, cardiac markers is an important tool to diagnose and provides prognostic information to treat the disease early on. Learn more about the different markers associated with CVD and what happens when the levels of the markers increases and decreases.

Author: Kristina Whitfield Undertakes marketing activities for Pivotal Scientific and their clients.

Kristina Whitfield

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. T

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 (MI). 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. In contrast it acts 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. Therefore, it is indicative for injury as result of anomalies like myocardial infarction, muscular dystrophy, malignant hyperthermia and myocarditis. 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 an indirect marker of intravascular fibrin formation, plasma D-dimer levels. High levels have been found in patients with overt thrombosis, pulmonary thrombo-embolism, and deep venous thrombosis. However, increased extravascular fibrin turnover after injury or infection 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 usually measured together with Troponin to identify MI and acute coronary syndrome in patients 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 neutrophil rich secretions, such as pus and 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. The protein is only detected in the blood after muscular injury. Hence, it is a sensitive marker for muscular damage (rhabdomyolysis). However, 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 pro-hormone 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 out 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. Currently, it has been universally used as indicator for myocardial infarction. Increased levels of serum cTnI also independently predict poor prognosis of critically ill patients acute coronary syndrome is absent.

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 M, 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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