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Can Biomarkers Predict Cardiovascular Disease Risk Before Diagnosis?

Published On 05/20/2024 8:58 AM
 

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Conventional risk factors for CVD, such as hypertension, diabetes mellitus, smoking, and hypercholesterolemia, have led to the development of risk prediction models and to major developments in therapy.
However, up to 20% of patients with coronary disease have no traditional risk factors, and 40% have only one.
Biomarkers are biological molecules found in blood, tissues, or other bodily fluids that can signal normal or abnormal processes in the body. Identifying individuals at risk for CVD is crucial for early intervention and prevention strategies. Biomarkers play a significant role in this regard by providing measurable indicators of disease risk, progression, and response to treatment.
 

Diagnosis of cardiovascular disease:

There are several medical tests and diagnostic procedures used to assess cardiovascular disease (CVD) and its risk factors. These tests are important tools for screening, diagnosing, and managing cardiovascular conditions. Here are some common tests used in the evaluation of cardiovascular disease:
 
  1. Electrocardiogram (ECG or EKG): An ECG is a quick and painless test that records the electrical signals in the heart. It can tell if the heart is beating too fast or too slowly.
  2. Lipid Profile (Cholesterol Panel): It includes measurements of total cholesterol, LDL cholesterol ("bad" cholesterol), HDL cholesterol ("good" cholesterol), and triglycerides. Abnormal lipid levels can indicate increased cardiovascular risk.
  3. Echocardiogram. This noninvasive exam uses sound waves to create detailed images of the heart in motion. It shows how blood moves through the heart and heart valves. An echocardiogram can help determine if a valve is narrowed or leaking.
  4. Cardiac catheterization. This test can show blockages in the heart arteries. A long, thin flexible tube (catheter) is inserted in a blood vessel, usually in the groin or wrist, and guided to the heart. Dye flows through the catheter to arteries in the heart. The dye helps the arteries show up more clearly on X-ray images taken during the test.
  5. Cardiac CT scan. In a cardiac CT scan, you lie on a table inside a doughnut-shaped machine. An X-ray tube inside the machine rotates around your body and collects images of your heart and chest.
  6. Cardiac MRI Scan. A cardiac MRI uses a magnetic field and computer-generated radio waves to create detailed images of the heart.
 

Pre-diagnosis Tests for Cardiovascular Disease:

Pre-diagnosis cardiovascular disease risk assessment focuses on evaluating the likelihood that an individual may develop cardiovascular disease (CVD) in the future, based on specific risk factors present before an official diagnosis of CVD is made. Although blood tests and lipid profiles are critical for identifying these risk factors, they do not definitively predict future cardiovascular events. These tests can indicate an increased likelihood of CVD based on present health indicators like cholesterol levels and blood pressure, but they cannot guarantee when, or if, a cardiovascular event might occur. It's important to interpret these tests as part of a broader assessment, considering other risk factors and individual health conditions to evaluate the overall risk for CVD more accurately.
 

The Critical Role of Biochemical Markers:

Building on the foundational assessment provided by pre-diagnosis testing, biochemical markers offer a more nuanced approach to understanding cardiovascular risks and managing potential outcomes. These markers play a crucial role in the accurate diagnosis of cardiac disease and, more importantly, in assessing risk and directing appropriate therapy that improves clinical outcomes. A wide range of biomarkers are measured and evaluated as indicators of normal biological processes and CVD risk. The following biomarkers are instrumental in the evaluation of cardiovascular disease and also in the research and development of drugs for treating these conditions.
 

Biochemical markers for cardiovascular disease:

NT - ProBNP:

A amino terminal pro B-type natriuretic peptide (BNP) test is a blood test. Higher- than-normal levels of BNP in your blood can be a sign that your heart isn’t working as it should. It can mean that your heart isn’t pumping enough blood through your body. NT-proBNP levels over 900 pg/mL may be a sign of heart failure. (Human NT - ProBNP ELISA Kit Cat #: BHE10803945)
 

ERK1:

Integration of cellular responses to extracellular cues is essential for cell survival and adaptation to stress. Extracellular signal-regulated kinase (ERK) 1 and 2 serve an evolutionarily conserved role for intracellular signal transduction that proved critical for cardiomyocyte homeostasis and cardiac stress responses. ERK1/2 phosphorylation early growth response-1 (Egr- 1), that regulates multiple molecular and cellular processes underpinning the pathogenesis of CVD by the zinc finger transcription factor. (Human ERK 1 ELISA Kit, Cat #: BHE10800856)
 

PTEN:

Downregulation of PTEN expression or inhibiting its biologic activity improves heart function, promotes cardiomyocytes proliferation, reduces cardiac fibrosis as well as dilation, and inhibits apoptosis following ischemic stress such as myocardial infarction. (Human PTEN ELISA Kit, Cat #: BHE10803702)
 

TEAD- 1:

TEA domain transcription factor 1 (TEAD1) induces cardiac fibroblasts cells remodeling. Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). Reports shows, Tead1 is required for maintaining adult cardiomyocyte function, and its loss results in lethal dilated cardiomyopathy. (Human TEAD1 ELISA Kit Cat #: BHE10807830)
 

NFKB:

A common deletion-allele in the promoter region of NFKB1 (Nuclear factor NF-kappa- B ) results in lower protein levels of the NF-kB p50 subunit. Lower protein level show inflammation risk factor for coronary heart disease (CHD). (Human NFKB ELISA Kit Cat #: BHE10804577)
 

ACE:

Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound, zinc- and chloride- dependent peptidyl dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a carboxy-terminal dipeptide. Angiotensin-converting enzyme (ACE) inhibitors are medicines that help relax the veins and arteries to lower blood pressure. ACE inhibitors prevent an enzyme in the body from making angiotensin 2, a substance that narrows blood vessels. This narrowing can cause high blood pressure and forces the heart to work harder. Angiotensin 2 also releases hormones that raise blood pressure. (Human ACE ELISA Kit Cat #: BHE10800175)
 

Adiponectin:

Adiponectin can protect against CVD by improving lipid metabolism, protecting vascular endothelial cells and inhibiting foam cell formation and vascular smooth muscle cell proliferation. Obesity-related cardiovascular disorders are strongly correlated with low levels of adiponectin. (Human ACE ELISA Kit Cat #: BHE10807808)
 

Angiogenin:

A high level of plasma angiogenin is associated with an increased risk of cardiovascular events and may play a significant role in the pathogenesis of CVD. (Human ACE ELISA Kit Cat #: BHE10806982)
 

NOS3:

Nitric oxide synthase 3 (NOS3) is an enzyme which is responsible for the production of the small molecule nitric oxide (NO). NOS3 is predominantly expressed in the endothelial tissue which lines the circulatory system and heart, where it plays a key role in regulation of NO The regulation of myocardial function by constitutive nitric oxide synthases (NOS) is important for the maintenance of myocardial Ca2+ homeostasis, relaxation and distensibility, and protection from arrhythmia and abnormal stress stimuli. (Human NOS3 ELISA Kit Cat #: BHE10805062)
 

APOE:

Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. ApoE2 and apoE4 increase the risk for heart disease with increasing atherogenic lipoprotein levels and LDL levels. (Human Apolipoprotein E ELISA Kit Cat #: BHE10804704)
Human Interleukin 6: IL-6 preserves vascular inflammation by promoting smooth muscle cell (SMC) proliferation and migration, endothelial dysfunction and the recruitment and activation of inflammatory mediators, which result in atherosclerotic plaque development. (Human IL-6 Cat #:BHE10807621)
 

PPLA:

Sarcoplasmic reticulum (SR) plays role in calcium cycling, Ca-transport and Ca-release and its malfunction is a universal characteristic of human heart failure. These SR functions are regulated by protein kinases and phosphatases. SR Ca-transport is mediated by the SR Ca-ATPase (SERCA2a) and its regulatory small phosphoprotein, phospholamban (PPLN). Its decrease expression increases the chance of cardiac failure. (Human phospholamban ELISA Kit Cat #: BHE10800184)
 
Biomarker Role in Cardiovascular Health Associated Conditions Diagnostic Value Clinical Implications
NT-ProBNP  Indicates heart stress and function Heart Failure High Guides treatment effectiveness; indicates prognosis
ERK1 Signal transduction in cardiomyocytes Cardiac Stress Response Moderate Potential target for therapeutic intervention
PTEN Regulates cardiac repair and apoptosis Myocardial Infarction, Cardiac Fibrosis Moderate to High Informs repair mechanisms post-injury
TEAD-1 Involved in cardiac fibroblast function Heart Failure, Cardiomyopathy Moderate Could guide fibrosis management and therapy
NFKB Controls inflammation linked to atherosclerosis Coronary Heart Disease High Targets for anti-inflammatory treatments
ACE Regulates blood pressure, vascular constriction Hypertension, Heart Failure High Directs choice of antihypertensive medications
Adiponectin  Modulates lipid metabolism and endothelial function Obesity-related Cardiovascular Disorders Moderate Used to assess risk in metabolic syndromes
Angiogenin Promotes angiogenesis Cardiovascular Disease Risk Low to Moderate Could predict severity and recovery in CVD
NOS3 Produces nitric oxide, regulates vascular tone Hypertension, Endothelial Dysfunction High Indicator for endothelial health therapy
APOE Influences cholesterol transport and metabolism Atherosclerosis, Hypercholesterolemia High Guides lipid-lowering strategies
IL-6 Promotes inflammation, atherosclerotic plaque Atherosclerosis, Vascular Inflammation High Marker for chronic inflammation management
PPLA Regulates calcium handling in cardiac cells Heart Failure Moderate Guides therapies targeting myocardial function

Table Description:

  • Biomarker: Name of the biomarker used in cardiovascular diagnostics.
  • Role in Cardiovascular Health: Primary biological or physiological role of the biomarker.
  • Associated Conditions: Cardiovascular conditions linked to the biomarker.
  • Diagnostic Value: Indicates how critical the biomarker is for diagnosing specific conditions.
  • Clinical Implications: Describes how the biomarker influences clinical decisions or treatment strategies.
 

Conclusion:

There are numerous CVD biomarkers that are currently available and that have clinical use as diagnostic, prognostic or predictive biomarkers in CVD. Several of these biomarkers have to be vigorously tested to assess their clinical utility across a varying spectrum of patients with atherosclerotic CVD. Some of more specific but only use in research for future developments.
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References:

1. Wang J., Tan G.-J., Han L.-N., Bai Y.-Y., He M., Liu H.-B. Novel biomarkers for cardiovascular risk prediction. J. Geriatr. Cardiol. JGC. 2017;14:135.

2. Dhingra R, Vasan RS. Biomarkers in cardiovascular disease: statistical assessment and section on key novel heart failure biomarkers. Trends Cardiovasc Med. 2017;27:123–133.

3. Lee DS, Vasan RS. Novel markers for heart failure diagnosis and prognosis. Curr. Opin. Cardiol. 2005;20:201–210.

4. https://www.mayoclinic.org/diseases-conditions/heart-disease/diagnosis-treatment/drc- 20353124#:~:text=An%20ECG%20is%20a%20quick,heart's%20activity%20during%20da ily%20activities.

5. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid =cardiac_biomarkers
This entry was posted in Application and Technique Notes

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