HEART MONTH – focusing on heart health and prevention

February is designated as “Heart Month,” a time to raise awareness about cardiovascular health, promoting healthy lifestyles, and encouraging prevention of heart disease. It aims to educate the public on the risk factors, symptoms, and treatments associated with heart-related conditions, highlighting the importance of maintaining a healthy heart through proper nutrition, regular exercise, avoiding smoking, managing stress, and monitoring blood pressure and cholesterol levels (1-3).

HEART MONTH – focusing on heart health and prevention

Biomarkers in cardiovascular disease

Biomarkers can serve as biochemical indicators that offer crucial insights into disease prognosis and progression, and in predicting the response to treatments. Biomarkers are also utilized in clinical trials or applied in toxicology, including preclinical drug safety evaluations. Advances in biomarker research have transformed how heart conditions are diagnosed and managed (4).

Biomedica offers a wide range of ELISA kits for the accurate measurement of biomarkers related to heart and cardiovascular diseases including NT-proBNP, Big Endothelin-1, FGF23, and markers related to oxidative stress.

• NT-proBNP – human (cat. no. SK-1204)
• NT-proBNP- rat  (cat. no. BI-1204R)
• NT-proANP – human, rodent (cat. no. BI-20892 )
• Big Endothelin-1 (cat. no. BI-20082H)
• FGF23 intact (cat. no. BI-20700)
• FGF23 c-terminal (cat. no. BI-20702)
• Endostatin
• Oxidized LDL (low density lipoprotein) antibodies, oLAB – (BI-20032)
• IL-6 (cat. no. BI-IL6)

 

NT-proBNP ∙ NT-proANP ∙ BigET-1 ∙ FGF23 ∙ Endostatin ∙ LRG1 ∙ oxLDL Antibodies ∙ IL-6

 

NT-proBNP (N-terminal pro b-type natriuretic peptide) is the inactive amino-terminal fragment cleaved from proBNP, a prohormone produced predominantly by ventricular myocytes in response to increased myocardial wall stress and volume overload. Due to its stability and longer half-life compared to active BNP, NT-proBNP serves as a sensitive and specific biomarker for the diagnosis of heart failure.  NT-proBNP is commonly used in the diagnosis and management of heart failure, reflecting increased intracardiac pressures and ventricular dilation (5-7). It aids in differentiating cardiac from non-cardiac causes of dyspnea, stratifying disease severity, guiding therapeutic decisions, and predicting morbidity and mortality outcomes in heart failure patients (8).

NT-proANP (N-terminal pro-atrial natriuretic peptide) is a biomarker released by the heart in response to atrial stretching and elevated blood volume. It is utilized to evaluate heart failure and detect cardiac stress, helping in the diagnosis and management of various cardiovascular conditions (9).

Big Endothelin-1 (Big ET-1) is a vasoconstrictive peptide and the precursor to Endothelin-1 (ET-1), which is the biologically active form. Elevated levels of Big ET-1 serve as an independent marker of heart failure in cases of congestive heart disease (10). Due to its longer half-life compared to ET-1 and its presence in circulation in equimolar amounts with ET-1, Big ET-1 is considered a more reliable biomarker.

Fibroblast Growth Factor-23 (FGF23) is a hormone involved in regulating phosphate metabolism. It has emerged as a potential biomarker for cardiovascular risk, with elevated circulating FGF23 levels being linked to adverse outcomes such as heart failure and arrhythmias (11, 12).

Endostatin, a fragment derived from collagen XVIII, is an extracellular matrix protein that plays a crucial role in the development of chronic kidney and heart diseases. In this study by Yaghoubi A et al, Endostatin levels were found to be elevated in patients hospitalized with acute dyspnea who had a history of chronic heart failure (CHF), and these elevated levels were associated with increased mortality at 3 months. Additionally, endostatin was linked to both 1-month and 3-month mortality in patients presenting with acute dyspnea who had no previous history of CHF (13, 14).

Leucine-rich alpha-2-glycoprotein (LRG) is a secreted protein that plays a significant role in pathological ocular neovascularization. It is also implicated in various conditions such as cardiovascular disease, diabetes, inflammatory disorders, and cancer. Recent research has identified LRG as an independent predictor of diastolic dysfunction (DD), due to myocardial fibrosis (15).

Oxidized LDL (low density lipoprotein) antibodies, oLAB 

Oxidized LDL (oxLDL) antibodies are directed against epitopes on oxidized low-density lipoprotein particles. OxLDL results from the oxidative modification of native LDL particles, involving lipid peroxidation and protein oxidation, which generate neoantigens recognized as foreign by the immune system (12). The production of anti-oxLDL antibodies, predominantly IgG and IgM subclasses, reflects ongoing oxidative stress and lipid peroxidation processes within atherosclerotic lesions. These antibodies can participate in immune complex formation, potentially influencing atherogenesis through pro-inflammatory or anti-inflammatory mechanisms. Elevated levels of anti-oxLDL antibodies have been correlated with the presence and progression of atherosclerotic plaques, making them valuable biomarkers for cardiovascular disease risk assessment. Their precise role in atherosclerosis pathophysiology remains complex, involving both protective clearance of modified lipoproteins and pro-inflammatory immune responses that may exacerbate vascular injury (16-18).

Interleukin-6 (IL-6)

IL-6 signaling plays a critical role in the inflammatory processes underlying cardiovascular disease (CVD). IL-6 is a cytokine that promotes inflammation, endothelial dysfunction, and plaque formation in atherosclerosis (15). It signals through its receptor complex, activating pathways such as JAK/STAT, which contribute to vascular inflammation and instability. Anti-IL-6 therapeutics, including monoclonal antibodies like tocilizumab, target this cytokine or its receptor to reduce inflammation. These agents have shown potential in lowering cardiovascular risk by modulating inflammatory responses, making IL-6 inhibition a promising strategy for managing CVD associated with chronic inflammation (19, 20).

 

Literature

1. 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Lichtenstein AH, Appel LJ, Vadiveloo M, Hu FB, Kris-Etherton PM, Rebholz CM, Sacks FM, Thorndike AN, Van Horn L, Wylie-Rosett J. Circulation. 2021 Dec 7;144(23):e472-e487. doi: 10.1161/CIR.0000000000001031. Epub 2021 Nov 2. PMID: 34724806.
2. A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now? Diab A, Dastmalchi LN, Gulati M, Michos ED. Vasc Health Risk Manag. 2023 Apr 21;19:237-253. doi: 10.2147/VHRM.S379874. PMID: 37113563; PMCID: PMC10128075.
3. Physical Activity Over the Lifecourse and Cardiovascular Disease. Perry AS, Dooley EE, Master H, Spartano NL, Brittain EL, Pettee Gabriel K. Circ Res. 2023 Jun 9;132(12):1725-1740. doi: 10.1161/CIRCRESAHA.123.322121. Epub 2023 Jun 8. PMID: 37289900; PMCID: PMC10254078.
4. Advancements in Biomarkers for Early Detection and Risk Stratification of Cardiovascular Diseases-A Literature Review. Nazir A, Nazir A, Afzaal U, Aman S, Sadiq SUR, Akah OZ, Jamal MSW, Hassan SZ. Health Sci Rep. 2025 May 26;8(5):e70878. doi: 10.1002/hsr2.70878. PMID: 40432692; PMCID: PMC12106349.
5. Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Tsutsui H, Albert NM, Coats AJS, Anker SD, Bayes-Genis A, Butler J, Chioncel O, Defilippi CR, Drazner MH, Felker GM, Filippatos G, Fiuzat M, Ide T, Januzzi JL Jr, Kinugawa K, Kuwahara K, Matsue Y, Mentz RJ, Metra M, Pandey A, Rosano G, Saito Y, Sakata Y, Sato N, Seferovic PM, Teerlink J, Yamamoto K, Yoshimura MJ Card Fail. 2023 May;29(5):787-804. doi: 10.1016/j.cardfail.2023.02.009. Epub 2023 Apr 17. PMID: 37117140.
6. Practical algorithms for early diagnosis of heart failure and heart stress using NT-proBNP: A clinical consensus statement from the Heart Failure Association of the ESC. Bayes-Genis A, Docherty KF, Petrie MC, Januzzi JL, Mueller C, Anderson L, Bozkurt B, Butler J, Chioncel O, Cleland JGF, Christodorescu R, Del Prato S, Gustafsson F, Lam CSP, Moura B, Pop-Busui R, Seferovic P, Volterrani M, Vaduganathan M, Metra M, Rosano G. Eur J Heart Fail. 2023 Nov;25(11):1891-1898. doi: 10.1002/ejhf.3036. Epub 2023 Sep 26. PMID: 37712339.
7. Essential biochemistry and physiology of (NT-pro)BNP. Hall C.Eur J Heart Fail. 2004;6:257–260. doi:10.1016/j.ejheart.2003.12.015.
8. Comprehensive Review of Cardiovascular Disease Management: Cardiac Biomarkers, Imaging Modalities, Pharmacotherapy, Surgical Interventions, and Herbal Remedies. Netala VR, Teertam SK, Li H, Zhang Z. A Cells. 2024 Sep 1;13(17):1471. doi: 10.3390/cells13171471. PMID: 39273041; PMCID: PMC11394358.
9. Prognostic value of NT-proANP levels on major cardiovascular outcomes in a 31-year follow-up study depends on baseline morbidity. Sakko S, Perkiömäki J, Ylitalo A, Huikuri H, Ukkola O, Koivunen P, Tapio J. Sci Rep. 2025 May 28;15(1):18660. doi: 10.1038/s41598-025-03819-6. PMID: 40436983; PMCID: PMC12119872.
10. Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure. Mo R, Yang YM, Yu LT, Tan HQ, Zhu J. Front Cardiovasc Med. 2021 Mar 11;8:629268. doi: 10.3389/fcvm.2021.629268. PMID: 33778022; PMCID: PMC7990871.
11. An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk. Vázquez-Sánchez S, Poveda J, Navarro-García JA, González-Lafuente L, Rodríguez-Sánchez E, Ruilope LM, Ruiz-Hurtado G. Front Physiol. 2021 Mar 9;12:632260. doi: 10.3389/fphys.2021.632260. PMID: 33767635; PMCID: PMC7985069.
12. Discharge FGF23 level predicts one year outcome in patients admitted with acute heart failure. Vergaro G, Aimo A, Taurino E, Del Franco A, Fabiani I, Prontera C, Masotti S, Musetti V, Emdin M, Passino C. Int J Cardiol. 2021 Aug 1;336:98-104. doi: 10.1016/j.ijcard.2021.05.028. Epub 2021 May 19. PMID: 34019969.
13. Endostatin in Renal and Cardiovascular Diseases. Li M, Popovic Z, Chu C, Krämer BK, Hocher B. Kidney Dis (Basel). 2021 Sep 9;7(6):468-481. doi: 10.1159/000518221. PMID: 34901193; PMCID: PMC8613550.
14. Association between endostatin and mortality in patients with acute dyspnoea, with or without congestive heart failure: a single-centre, prospective, observational study. Yaghoubi A, Heijl C, Khoshnood AM, Wändell PE, Carlsson AC, Wessman T. BMJ Open. 2025 Jan 11;15(1):e085238. doi: 10.1136/bmjopen-2024-085238. PMID: 39800400; PMCID: PMC11752042.
15. Leucine-Rich Alpha-2-Glycoprotein: A Novel Predictor of Diastolic Dysfunction. Loch A, Tan KL, Danaee M, Idris I, Ng ML. Biomedicines. 2023 Mar 20;11(3):944. doi: 10.3390/biomedicines11030944. PMID: 36979923; PMCID: PMC10045934.
16. Immune response to lipoproteins in atherosclerosis. Samson S, Mundkur L, Kakkar VV. 2012;2012:571846. doi: 10.1155/2012/571846. Epub 2012 Aug 23. PMID: 22957222; PMCID: PMC3432325.
17. Antibodies against human oxidized low-density lipoprotein (LDL) as markers for human plasma modified lipoproteins. Radulescu L, Stancu C, Antohe F. Med Sci Monit. 2004 Jul;10(7):BR207-14. Epub 2004 Jun 29. PMID: 15232494.
18. Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy .Hartley A, Haskard D, Khamis R. Trends Cardiovasc Med. 2019 Jan;29(1):22-26. doi: 10.1016/j.tcm.2018.05.010. Epub 2018 Jun 4. PMID: 29934015.
19. IL-6 and Cardiovascular Risk: A Narrative Review. Mehta NN, deGoma E, Shapiro MD. Curr Atheroscler Rep. 2024 Nov 26;27(1):12. doi: 10.1007/s11883-024-01259-7. PMID: 39589436; PMCID: PMC11599326.
20. Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease. Ridker PM, Rane M. Circ Res. 2021 May 28;128(11):1728-1746. doi: 10.1161/CIRCRESAHA.121.319077. Epub 2021 May 17. PMID: 33998272.