Prognostic role of osteopontin in assessing the risk of adverse cardiovascular and osteoporetic events

   The purpose of the study. To evaluate the prognostic significance of osteopontin (OPN) in determining the risk of adverse cardiovascular and osteoporotic events in women with chronic heart failure (CHF) comorbid with type 2 diabetes mellitus (DM2) and osteoporosis during 36 months of observation.

   Material and methods. The study involved 90 women aged 50-65 years with CHF, type 2 diabetes mellitus and osteoporosis, divided into two groups depending on the initial concentration of OPN in the blood: group 1 – with OPN level ≤23,5 ng/ml and group 2 – with OPN level > 23,5 ng/ml. The combined endpoint was death from common causes, an increase in the functional class (FC) of CHF, the development of non-fatal myocardial infarction (MI), pulmonary embolism, stroke, cases of hospitalization with decompensated CHF and osteoporotic bone fractures.

   Results. In women with a higher level of OPN (> 23,5 ng/ml), the risk of developing cumulative complications was significantly higher (OR = 4,98, p = 0,001). Analysis of individual events revealed a significant increase in the risk of progression of FC (OR = 4,13, p = 0,001) and decompensation of CHF (OR = 2,67, p = 0,021), development of MI (OR = 5,38, p= 0,019) and osteoporotic fractures (OR = 4,86, p = 0,003) with an initial concentration of OPN > 23,5 ng/ml during 36 months of observation. The level of OPN above 23,5 ng/ml with sensitivity = 82 % and specificity = 69 % (area under the curve = 0,86, p = 0,001) predicts the occurrence of adverse cardiovascular events for the combined endpoint, and with sensitivity = 75 % and specificity = 65 % (area under the curve = 0,74, p = 0,001) – the development of osteoporotic fractures during three years of observation.

   Conclusion. Osteopontin is a risk factor for the development of adverse cardiovascular events and bone fractures in women with CHF, type 2 diabetes and osteoporosis.

1. Gomez-Delgado F., Raya-Cruz M., Katsiki N, et al. Residual cardiovascular risk: When should we treat it? Eur J Intern Med. 2024 Feb. 120. 17–24. doi: 10.1016/j.ejim.2023.10.013.

2. Boulet J., Sridhar V.S., Bouabdallaoui N., et al. Inflammation in heart failure: pathophysiology and therapeutic strategies. Inflamm Res. 2024 May. 73 (5). 709-723. doi: 10.1007/s00011-023-01845-6.

3. Icer M.A., Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin. Clin Biochem. 2018 Sep. 59. 17–24. doi: 10.1016/j.clinbiochem.2018.07.003.

4. Zoroddu S., Lorenzo B.D., Paliogiannis P. et al. Osteopontin in rheumatic diseases : A systematic review and meta-analysis. Clin Chim Acta. 2025 Mar 15. 570. 120209. doi: 10.1016/j.cca.2025.120209.

5. Kadoglou N.P.E., Khattab E., Velidakis N., et al. The Role of Osteopontin in Atherosclerosis and Its Clinical Manifestations (Atherosclerotic Cardiovascular Diseases) – A Narrative Review. Biomedicines. 2023 Nov 29. 11 (12). 3178. doi: 10.3390/biomedicines11123178.

6. Lok Z.S.Y., Lyle A.N. Osteopontin in Vascular Disease. Arterioscler Thromb Vasc Biol. 2019 Apr. 39 (4). 613-622. doi: 10.1161/ATVBAHA.118.311577.

7. Carbone F., Meessen J., Magnoni M. et al. Osteopontin as Candidate Biomarker of Coronary Disease despite Low Cardiovascular Risk: Insights from CAPIRE Study. Cells. 2022 Feb 15. 11(4). 669. doi: 10.3390/cells11040669.

8. Yousefi K., Irion C.I., Takeuchi L.M., et al. Osteopontin Promotes Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway. J Am Coll Cardiol. 2019 Jun 4. 73 (21). 2705-2718. doi: 10.1016/j.jacc.2019.02.074.

9. Cicekli I., Saglam D., Takar N. A New Perspective on Metabolic Syndrome with Osteopontin : A Comprehensive Review. Life (Basel). 2023 Jul 22. 13 (7). 1608. doi: 10.3390/life13071608.

10. Shirakawa K., Endo J.., Kataoka M. et al. MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction. J Am Heart Assoc. 2020 Sep 15. 9 (18). e017071. doi: 10.1161/JAHA.120.017071.

11. Kusuyama T., Yoshiyama M., Omura T. et al. Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction. J Pharmacol Sci. 2005 Jul. 98 (3). 283-9. doi: 10.1254/jphs.fp0050056.

12. Elbaz M., Grazide M.H., Bataille V. et al. Temporal trajectory and left ventricular ejection fraction association of eight circulating biomarkers in first acute myocardial infarction patients: a 12-month prospective cohort study. Eur Heart J Open. 2024 Oct 15. 4 (5). oeae090. doi: 10.1093/ehjopen/oeae090.

13. Maniatis K., Siasos G., Oikonomou E. et al. Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients. Curr Vasc Pharmacol. 2020. 18 (5). 523–530. doi: 10.2174/1570161117666191022095246.

14. Kuprytė M., Lesauskaitė V., Siratavičiūtė V. et al. Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure. Int J Mol Sci. 2024 Jul 28. 25 (15). 8240. doi: 10.3390/ijms25158240.

15. Hilgendorf I., Frantz S., Frangogiannis N.G. Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities. Circ Res. 2024 Jun 7. 134 (12). 1718-1751. doi: 10.1161/CIRCRESAHA.124.323658.

16. Kruszewska J., Cudnoch-Jedrzejewska A., Czarzasta K. Remodeling and Fibrosis of the Cardiac Muscle in the Course of Obesity-Pathogenesis and Involvement of the Extracellular Matrix. Int J Mol Sci. 2022 Apr 11. 23 (8). 4195. doi: 10.3390/ijms23084195.

17. Bräuninger H., Krüger S., Bacmeister L. et al. Matrix metalloproteinases in coronary artery disease and myocardial infarction. Basic Res Cardiol. 2023 May 9. 118 (1). 18. doi: 10.1007/s00395-023-00987-2.

18. Mamazhakypov A., Sartmyrzaeva M., Sarybaev A.S., et al. Clinical and Molecular Implications of Osteopontin in Heart Failure. Curr Issues Mol Biol. 2022 Aug 11. 44 (8). 3573–3597. doi: 10.3390/cimb44080245.

19. Robinson J.A., Toribio M., Quinaglia T. et al. Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV. AIDS. 2023 Feb 1. 37 (2). 305–310. doi: 10.1097/QAD.0000000000003417.

20. Tang Z., Xia Z., Wang X., et al. The critical role of osteopontin (OPN) in fibrotic diseases. Cytokine Growth Factor Rev. 2023 Dec. 74. 86–99. doi: 10.1016/j.cytogfr.2023.08.007.