Cardiac Biomarker Overview - Assay Solution Biomar… · FAS Antibody AS-P01722 Fas Antibody...

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Cardiac Biomarker Overview

Biomarkers generally represent a biochemical change at a tissue or a body organ level. Therefore, they are associated with a

biologic or pathologic process. However, the clinical outcomes from these processes in terms of biomarkers as disease indicators

could be different. For example, troponin elevation up to a certain degree can be present in congestive heart failure, pulmonary

embolism and more conventionally and classically in acute myocardial ischemia/infarction. Moreover, biomarkers that are

intended to be used in clinical practice can be useful if changes in their levels adequately mirror improvement in the disease

process itself when the disease is being treated (predictive biomarkers), thereby reflecting an improvement in patient outcome.

For example, blood B-type natriuretic peptide (BNP) concentrations increase with worsening heart failure status. Additionally, a

clinically useful biomarker should be able to provide meaningful information about prognosis and/or guide clinical decision

making and not simply duplicate information that is already available clinically. Derivation and validation to associate a

biomarker to a disease process should also be carried out in different subsets of population. In general, biomarkers predicting

disease risk perform much better in the derivation cohort compared to a validation cohort. Universal biomarker standards have

also been proposed according to their intended use for disease diagnosis and prognosis.

Newer cardiovascular biomarkers under evaluation

There are numerous CVD biomarkers under evaluation and a detailed review is beyond the scope of this review. Several

classifications exist currently to classify CVD biomarkers. Most commonly, biomarkers can be grouped based on disease

specificity such as biomarkers of heart failure (BNP, N-terminal prohormone of brain natriuretic peptide [NT-proBNP], atrial

natriuretic peptide [ANP], ST-2 etc), of atherosclerotic coronary disease (troponin T or I, creatinine phosphokinase-MB etc.), or

they can be grouped according to their use such as in acute changes (copeptin, high sensitivity Troponin, galectin-3, ST2) versus

in the chronic stage of CVD to estimate prognosis (coronary calcium by CT). Alternatively, CVD biomarkers can be grouped

according to the pathologic process they represent, such as inflammation (e.g., C-reactive protein, interleukin 6, Fibrinogen,

monocyte chemotactic protein-1, tumor necrosis factor alpha etc) oxidative stress (e.g., isoprostanes), and metabolic (e.g.,

lipoprotein (a), low-density lipoproteins, high density lipoprotein, ApoB 100, Lipoprotein-associated phospholipase A2,

Homocysteine, vitamin D, fibroblast growth factor 23, adiponectin, glycated hemoglobin, haptoglobin etc). In the next section we

present some examples of novel biomarkers which are currently being investigated for heart failure and emphasize some of the

key concepts influencing their use in clinical practice.

Major Novel Heart Failure Biomarkers

Individual investigators have proposed classification of heart failure biomarkers according to the pathologic process they

indicate. Previous reviews have described relevant limitations of novel heart failure biomarkers for use as treatment guidance and

sex differences when using these biomarkers for clinical use. Further consensus statements have recommended establishing a


consortium to allow novel biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and

hypotheses to be generated for testing each biomarker in biomarker-guided trials.

Myocardial stretch

Proudct Catalog #

Troponin I (TnI) Human Troponin I (cTnI) ELISA kit inquiry

Troponin T (TnT) Troponin T Antibody (monoclonal) ASA-B1928

Recombinant human cTnT inquiry

Porcine cTnT, native inquiry

Human cTnT ELISA kit inquiry

Troponin C (TnC) Troponin IC Human AS-P05675

TNC Human AS-P05545

TNC Rabbit AS-P05546

Human cTnC ELISA kit inquiry

H-FABP/FABP3 Human FABP3 ELISA Kit AYQ-E10919

FABP3 Human AS-P01690

CK-MB CK-MB ELISA kit inquiry

sTRAIL Human TRAIL/TNFSF10 ELISA Kit AYQ-E11184

TRAIL Antibody ASA-B1908

TRAIL Antibody ASA-B1909

TRAIL Human Protein AS-P05652

HSP60 Human Total HSP60 ELISA Kit AYQ-E10654

Mouse Total HSP60 ELISA Kit AYQ-E10655


Porcine Total HSP60 ELISA Kit AYQ-E10658

Canine Total HSP60 ELISA Kit AYQ-E10657

HSP60 Antibody ASA-B0916

Hsp60 Antibody ASA-B0917

HSP60 Antibody (monoclonal) ASA-B0915

Inflammation

CRP CRP (19-224 a.a) Human AS-P01126

CRP Antibody AS-P01127

CRP Human AS-P01128

CRP Human Recombinant AS-P01129

CRP Rat AS-P01130

Human C-Reactive Protein/CRP ELISA Kit AYQ-E11268

ST2 Human ST2/IL-33 R ELISA Kit AYQ-E11208

TNF alpha Anti TNF alpha Antibody (polyclonal) A0211B

Mouse TNF alpha Antibody ASA-B1308

TNF alpha Antibody ASA-B1882

TNF alpha Antibody ASA-B1883

GDF-15 Human GDF-15 ELISA Kit AYQ-E11222

GDF15 D Human AS-P01975

GDF15 Human AS-P01976

GDF15 Human, His AS-P01977

GDF15 Mouse AS-P01978

Fas/APO-1 Anti Fas Antibody (polyclonal) A0217B

FAS Antibody AS-P01722

Fas Antibody ASA-B0683

Fas Antibody ASA-B0684

http://assaysolution.com/hsp60-antibody


FAS Human AS-P01724

Fas Ligand Antibody ASA-B0685



Human Fas/TNFRSF6/CD95 ELISA Kit AYQ-E11079

Human CD178 (Fas-L) Antibody ASB-G0586

Human CD178 (Fas-L) APC Antibody ASB-G0054

Human CD178 (Fas-L) Biotin Antibody ASB-G0055

LP-PLA2 Lipoprotein-associated phospholipase A2 (Lp-PLA2),

in vitro, antibody inquiry

Recombinant human lipoprotein-associated

phospholipase A2 (Lp-PLA2) inquiry

YKL-40/CHI3L1 Human Chitinase 3-like 1 ELISA Kit AYQ-E11262

CHI3L1 Human AS-P00950

CHI3L1 Antibody AS-P00949

CHI3L1 (22-383) Human AS-P00948

IL-1 Canine IL-1 RAPL1/IL-1 R8 ELISA Kit AYQ-E10074

Human IL-1 alpha/IL-1F1 ELISA Kit AYQ-E11101

Human IL-1 beta/IL-1F2 ELISA Kit AYQ-E10802

Human IL-1 RAcP/IL-1 R3 ELISA Kit AYQ-E10969

Human IL-1 RAPL1/IL-1 R8 ELISA Kit AYQ-E10071

Human IL-1 RI ELISA Kit AYQ-E11217

Human IL-1 RII ELISA Kit AYQ-E11156

Human IL-1ra/IL-1F3 ELISA Kit AYQ-E11310

Mouse IL-1 RAPL1/IL-1 R8 ELISA Kit AYQ-E10072

Porcine IL-1 RAPL1/IL-1 R8 ELISA Kit AYQ-E10075

Rat IL-1 RAPL1/IL-1 R8 ELISA Kit AYQ-E10073


Osteoprotegerin(OPG) Human Osteoprotegerin/TNFRSF11B ELISA Kit AYQ-E10925

Osteoprotegerin Antibody ASA-B1441

Pentraxin Canine Pentraxin 2/SAP ELISA Kit AYQ-E10424

Human Pentraxin 2/SAP ELISA Kit AYQ-E10421

Human Pentraxin 3/TSG-14 ELISA Kit AYQ-E10851

Mouse Pentraxin 2/SAP ELISA Kit AYQ-E10422

Porcine Pentraxin 2/SAP ELISA Kit AYQ-E10425

Rat Pentraxin 2/SAP ELISA Kit AYQ-E10423

Procalcitonin Human Procalcitonin ELISA Kit AYQ-E11280

Procalcitonin Canine AS-P04456

Procalcitonin Human AS-P04457

Procalcitonin Human, His AS-P04458

Procalcitonin Mouse AS-P04459

Procalcitonin Porcine AS-P04460

Procalcitonin Rat AS-P04461

Procalcitonin Rhesus AS-P04462

sEndoglin Endoglin Human, His AS-P01577

Human CD166 (Endoglin) PE Antibody ASB-G0010

PR3 PR3 (c-ANCA) ELISA kit inquiry

Adiponectin Adiponectin Antibody ASA-B0040

Adiponectin Antibody ASA-B0041

Adiponectin Antibody ASA-B0042

Human Adiponectin/Acrp30 ELISA Kit AYQ-E10899

Neurohormonal therapy

Norepinephrine N/A

Renin Human Renin ELISA Kit AYQ-E11243


Angiotensin II Angiotensin AS-P00209

Angiotensin Converting Enzyme 1 Antibody ASA-B0087

Angiotensin Converting Enzyme 1 Antibody ASA-B0088

Aldosterone N/A

Arginine vasopressin Vasopressin AS-P05855

AVPR1A Antibody ASA-B0181

Copeptin N/A

Endothelin-1 N/A

Urocortin N/A

Chromogranin A Chromogranin A Antibody ASA-B0453

CHGA Antibody AS-P00943

CHGA Human AS-P00944

CHGA Human, GST AS-P00945

CHGA Human, His AS-P00946

Human Chromogranin A ELISA Kit AYQ-E11150

Chromogranin B CHGB Human AS-P00947

MR-proADM N/A

Extracellular Matrix Remodeling

MMP-2 Canine MMP-2 ELISA Kit AYQ-E10518

Human MMP-2 ELISA Kit AYQ-E10515

MMP-2 Human, HEK AS-P03664

Mouse MMP-2 ELISA Kit AYQ-E10516

Porcine MMP-2 ELISA Kit AYQ-E10519

Rat MMP-2 ELISA Kit AYQ-E10517


MMP-3 Human Total MMP-3 ELISA Kit AYQ-E10811

MMP 3 Human AS-P03651

MMP 3 Human, GST AS-P03652

MMP 3 Human, HEK AS-P03653

MMP-9 Human MMP-9 ELISA Kit AYQ-E11249

MMP 9 Human AS-P03658

MMP 9 Rabbit AS-P03659

ProMMP 9 Human AS-P04476

TIMP1 Bovine TIMP-1 ELISA Kit AYQ-E10736

Human TIMP-1 ELISA Kit AYQ-E10735

TIMP1 Antibody ASA-B1862

TIMP1 Human AS-P05520

TIMP1 Human, HEK AS-P05521

TIMP1 Human, Sf9 AS-P05522

TIMP1 Mouse AS-P05523

TIMP1 Rat AS-P05524

IL-6 Human IL-6 ELISA Kit AYQ-E11056

Human IL-6 R alpha ELISA Kit AYQ-E11090

IL-6 Antibody ASA-B0992

IL-6 Matched Antibody Pair ASC-025P

IL-6 Mouse, His AS-P03043

IL-6 PAT1F10AT Antibody AS-P03044

IL 6 Antibody AS-P02953

IL 6 Human AS-P02954

IL 6 Human, CHO AS-P02955

IL 6 Human, HEK AS-P02956


IL 6 Human, His AS-P02957

IL 6 Mouse AS-P02958

IL 6 Mouse, Sf9 AS-P02959

IL 6 Rat AS-P02960

IL 6 Rhesus Macaque AS-P02961

sIL 6R Human AS-P05081

Collagen propetides, PICP Canine Pro-Collagen I alpha 1 ELISA Kit AYQ-E10379

Human Pro-Collagen I alpha 1 ELISA Kit AYQ-E10376

Mouse Pro-Collagen I alpha 1 ELISA Kit AYQ-E10377

Porcine Pro-Collagen I alpha 1 ELISA Kit AYQ-E10380

Rat Pro-Collagen I alpha 1 ELISA Kit AYQ-E10378

N-terminal collagen type III peptide,

PIIINP N/A

Myostatin Myostatin Antibody AS-P03766

Myostatin Human AS-P03767

Myostatin Human, HEK AS-P03768

Myostatin Human, His AS-P03769

Myostatin Human, Plant AS-P03770

Myostatin Propeptide Human AS-P03771

Myostatin Propeptide Human, HEK AS-P03772

Syndecan-4 Human Syndecan-4 ELISA Kit AYQ-E10872

Syndecan 4 Antibody ASA-B1824

Galectin-3 Bovine Galectin-3 ELISA Kit AYQ-E10756

Galectin 3 Antibody ASA-B0755

Galectin 3 Antibody ASA-B0756

Human Galectin-3 ELISA Kit AYQ-E10833

Human Galectin-3 ELISA Kit AYQ-E10755


Human Galectin-3BP/MAC-2BP ELISA Kit AYQ-E11227

Oxidative stress

Oxidized LDL N/A

MPO MPO Human AS-P03683

Myeloperoxidase Antibody ASA-B1336

Myeloperoxidase Antibody ASA-B1337

Urinary biopyrrins N/A

Urinary and plasma isoprostanes N/A

Urinary 8-hydroxyl-2'-deoxygunosine N/A

Plasma malondialdehyde N/A

Myocyte injury

BNP BNP Human AS-P00517

BNP Human AS-P00518

BNP Human, His AS-P00519

NT-proBNP Human NT Pro-BNP ELISA Kit AYQ-E11044

Human recombinant NT-proBNP (amino terminal

human brain natriuretic peptide precursor) inquiry

MR-proANP N/A

ST2 Dengue NS1 ST2 AS-P01350

Human ST2/IL-33 R ELISA Kit AYQ-E11208

GDF-15 GDF15 D Human AS-P01975

GDF15 Human AS-P01976

GDF15 Human, His AS-P01977

GDF15 Mouse AS-P01978


Human GDF-15 ELISA Kit AYQ-E11222

Others

IGFBP4 Human IGFBP-4 ELISA Kit AYQ-E11011

IGFBP 4 Human AS-P02778

Myoglobin Myoglobin Antibody ASA-B1339

Myoglobin Antibody ASA-B1340

Myoglobin Antibody AS-P03762

Myoglobin Antibody (monoclonal) ASA-B1338

Myoglobin His Human AS-P03763

Myoglobin Human AS-P03764

Myoglobin Human AS-P03765

D-dimer Human D-Dimer ELISA Kit AYQ-E11342

sCD40L sCD40L Human AS-P04939

sCD40L Human, His AS-P04940

sCD40L Mouse AS-P04941

sCD40L Mouse, sf9 AS-P04942

Cystatin C Cystatin C Antibody ASA-B0558

Human Cystatin C ELISA Kit AYQ-E11248

Human serum albumin Human Serum Albumin ELISA Kit AYQ-E11199

SAA SAA Human AS-P04905

SAA1 Human AS-P04906

SAA1 Human, His AS-P04907

SAA1 Monkey AS-P04908

SAA4 Human AS-P04909

RBP4 Canine RBP4 ELISA Kit AYQ-E10780

Human RBP4 ELISA Kit AYQ-E10929


Human RBP4 ELISA Kit AYQ-E10779

RBP4 Antibody AS-P04697

RBP4 Antibody ASA-B1617

RBP4 Human AS-P04698

RBP4 Human, His AS-P04699

Glycogen phosphorelase isozyme BB

(GPBB) GPBB Human AS-P02142

S100B Bovine S100B ELISA Kit AYQ-E10791

Human S100B ELISA Kit AYQ-E10787

Mouse S100B ELISA Kit AYQ-E10788

Porcine S100B ELISA Kit AYQ-E10790

Rat S100B ELISA Kit AYQ-E10789

S100b Human AS-P04894

S100B Human, GST AS-P04895

S100B Human, His AS-P04896

S100b Mouse AS-P04897

S100b Mouse, His AS-P04898

S100b Rhesus Macaque AS-P04899

•Myocardial stretch leads to production of pro BNP compound that is later broken down into BNP and NT proBNP (inert form).

Higher concentration of BNP in the blood of a patient who presents to an emergency room is associated with greater probability

of a diagnosis of heart failure. Moreover, higher BNP concentration on admission to the hospital is also associated with greater

in-hospital mortality. NT proBNP, which is a more stable form of BNP, is also predictive of a diagnosis of heart failure.

Medications and other therapies utilized currently to treat heart failure are also known to reduce BNP levels effectively;

however with some exceptions. It is important to understand, however, that BNP levels are inversely associated with obesity,

and may also be influenced by presence of kidney disease. Circulating ANP on the other hand is overall more unstable in blood

compared to BNP or NT proBNP and therefore has a limited use in diagnosis or prognosis. However, a mid-regional ANP, a

prohormone isolated from mid region of the molecule (MR-proANP) has shown promise in diagnosis of heart failure in a


multinational biomarker study (BACH trial) in acute heart failure patients although its added incremental utility over BNP for

diagnostic purposes is yet to be fully proven. So far, the research shows that MR-proANP could be of added advantage for the

diagnosis of heart failure in obese, elderly and patients with renal disease when compared to BNP. MR-proANP is also being

evaluated for prognosis of heart failure as well.

•Cardiomyocyte necrosis releases Troponin I or T (cardiac isomers of proteins from troponin-tropomyosin complex) in

circulation of an individual and they are typically useful in detection of myocardial ischemia. High sensitive assays of Troponin

T and I, however, are also elevated in the blood of patients with severe heart failure and therefore have been appropriately

studied for the prediction of heart failure and for prognostication in those with established heart failure. Another biomarker that

is associated with both ischemic and heart failure is Copeptin, a precursor protein of arginine vasopressin (ADH). Copeptin

levels are elevated in the immediate post ischemic period and also correlate with higher risk of death and new-onset heart

failure. Some investigators have reported the superiority of copeptin over BNP and NT-proBNP concentrations for predicting

death, although the caveat is that these biomarkers are often closely related.

•Neutrophil gelatinase-associated lipocalin (NGAL), another glycoprotein covalently bound to matrix metaloproteinase-9, is

released by renal tubular cells in response to renal inflammation and injury, and it has also shown to offer added prognostic and

diagnostic value along with BNP in the GALLANT trial. However, subsequent studies with corresponding biomarker data from

other heart failure trials did not replicate these findings. Therefore, the clinical utility of this biomarker above and beyond other

commonly used biomarkers in chronic heart failure patients with renal injury is questionable.

•Galectin-3 is an exciting biomarker with an important role in development and regulation of cardiac fibrosis and remodeling. In

patients diagnosed with acute decompensated heart failure, blood Galectin-3 level has shown to be predictive of mortality on

short-term follow up. In fact, investigators have also suggested the superiority of galectin-3 or enhanced predictive power for

mortality when used along with BNP levels in patients with both preserved and reduced left ventricular ejection fraction.

Overall, researchers currently underscore the added advantage of using a multimarker approach in heart failure; however, the

independent use of Galectin-3 alone in heart failure patients is not as well supported by literature for the prediction of

prognosis. Other markers of extracellular matrix such as metalloproteins which degrade collagen (MMPs), specific tissue

inhibitors of metalloproteins (TIMPs), procollagen type III amino-terminal propeptide (PIIINP), or procollagen type I carboxy

terminal peptide (PICP) that have been traditionally related to hypertensive heart disease are currently explored as biomarkers

with implications for assessing disease severity, prognosis and response to treatment among patients with heart failure with

preserved ejection fraction (HFpEF).

•Additionally, higher levels of blood Procalcitonin, an acute phase reactant, have been associated with a greater likelihood of the

presence of infection in patients with heart failure. Therefore, procalcitonin can sometimes be useful for excluding infections or

pneumonia in patients seen in the emergency room with shortness of breath who are suspected to have a diagnosis of acute on

chronic heart failure.


•ST-2 is a receptor from interleukin family (IL-33) with two gene forms – soluble (sST2) and transmembrane form. Like other

biomarkers, blood ST-2 levels are also shown to predict mortality and new onset heart failure. Researchers have also examined

the predictive ability of ST-2 levels complementary to other traditional risk factors and NT-proBNP levels in ST-elevation

myocardial infarction patients. It also has a role over traditional heart failure risk factors for determining prognosis. These

findings have led researchers to explore the use of ST-2 as part of a multi-marker approach for assessing the prognosis of

patients with heart failure.

•Mid-regional pro-adernomedullin (MR-proADM) is a stable prohormone fragment of adernomedullin, a vasodilatory peptide,

and elevated circulating levels are strongly associated with the presence of chronic heart failure. MR-proADM has been shown

to be superior to both BNP and NT-proBNP in predicting 90-day mortality among patients with dyspnea and heart failure.

•Growth differentiation factor – 15 – is classified as a biomarker with anti-hypertrophic effects (apoptosis) and investigators have

linked the elevated levels of this biomarker to assess prognosis in chronic heart failure patients and among community dwelling

adults as a predictor of all-cause mortality, including non-cardiovascular mortality above and beyond the information provided

by blood NT-proBNP and C-reactive protein levels.

Cardiac Biomarker Overview - Assay Solution Biomar… · FAS Antibody AS-P01722 Fas Antibody...

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Transcript of Cardiac Biomarker Overview - Assay Solution Biomar… · FAS Antibody AS-P01722 Fas Antibody...