Factors of Long-Term Prognosis for Cardiovascular Complications in Patients After Acute Myocardial Infarction, Based on the Plasma Proteome

Aim. To study the plasma proteome of patients with type 1 acute myocardial infarction (AMI) to identify potential markers for long-term prognosis of the risk for developing cardiovascular complications.
Material and methods. The study included 64 patients with type 1 AMI with and without ST segment elevation who underwent primary percutaneous coronary intervention upon admission. The following information on cardiovascular events was collected for 36 months after admission: death from cardiovascular pathology, recurrent AMI, stroke, repeat myocardial revascularization and/or endarterectomy. Peripheral blood sampling followed by a plasma proteome analysis using chromatography-mass spectrometry was performed in all patients before hospitalization.
Results. During 36 months after hospitalization, cardiovascular complications were detected in 23 (36%) patients. These patients were included in the group with an unfavorable prognosis, while the remaining patients made up the group with a positive prognosis. A mass spectrometric analysis of the plasma proteome and comparison of the groups identified seven differentially represented proteins. Also, a multivariate regression analysis, ROC curves, and Kaplan-Meier models showed that four proteins (apolipoprotein C1, complement factor H, di-N-acetylchitobiase, and ficolin-2) were predictors of the risk for developing cardiovascular complications in the long term. An integrated parameter was developed that took into account the plasma concentrations of all four above proteins. This parameter was used to construct a model for assessing the risks of unfavorable long-term prognosis in AMI patients with a sensitivity of 87% and a specificity of 78%.
Conclusion. The study results demonstrated that plasma concentrations of apolipoprotein C1, complement factor H, di-N-acetylchitobiase, and ficolin-2 are reliable prognostic markers for assessing the risks of cardiovascular events in patients with AMI in the long term.

1. Martin SS, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL et al. 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation. 2024;149(8):e347–913. DOI: 10.1161/CIR.0000000000001209

2. Lee SH, Hong YJ, Ahn Y, Jeong MH. Past, Present, and Future of Management of Acute Myocardial Infarction. Journal of Cardiovascular Intervention. 2023;2(2):51–65. DOI: 10.54912/jci.2022.0023 3. Moras E, Yakkali S, Gandhi KD, Virk HUH, Alam M, Zaid S et al. Complications in Acute Myocardial Infarction: Navigating Challenges in Diagnosis and Management. Hearts. 2024;5(1):122–41. DOI: 10.3390/hearts5010009

3. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal. 2018;39(2):119–77. DOI: 10.1093/eurheartj/ehx393

4. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021–104. DOI: 10.1093/eurheartj/ehy339

5. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal. 2021;42(14):1289–367. DOI: 10.1093/eurheartj/ehaa575

6. Ministry of Health of Russian Federation. Clinical recomendations. Acute coronary syndrome with ST segment elevation electrocardiogram. Av. at: https://cr.minzdrav.gov.ru/recomend/157_2. 2020.

7. Ministry of Health of Russian Federation. Clinical recomendations. Acute coronary syndrome without ST segment elevation electrocardiogram. Av. at: https://cr.minzdrav.gov.ru/recomend/157_3. 2020.

8. Ezhov MV, Sergienko IV, Kryzhanovskiy SM, Manko KS, Timoshina EV. Comparative Efficacy and Safety of Statin Monotherapy and Statin plus Ezetimibe Combination in a Real-World Setting. Diseases. 2023;11(4):168. DOI: 10.3390/diseases11040168

9. Yao J, Xie Y, Liu Y, Tang Y, Xu J. Prediction Factors of 6-Month Poor Prognosis in Acute Myocardial Infarction Patients. Frontiers in Cardiovascular Medicine. 2020;7:130. DOI: 10.3389/fcvm.2020.00130

10. Huang Y, Zhang Q, Li P, Chen M, Wang R, Hu J et al. The prognostic nutritional index predicts all-cause mortality in critically ill patients with acute myocardial infarction. BMC Cardiovascular Disorders. 2023;23(1):339. DOI: 10.1186/s12872-023-03350-4

11. Byeon J, Choo EH, Choi IJ, Lee KY, Hwang B-H, Kim CJ et al. Office-Visit Heart Rate and Long-Term Cardiovascular Events in Patients with Acute Myocardial Infarction. Journal of Clinical Medicine. 2023;12(11):3734. DOI: 10.3390/jcm12113734

12. Abu-Assi E, López-López A, González-Salvado V, Redondo-Diéguez A, Peña-Gil C, Bouzas-Cruz N et al. The Risk of Cardiovascular Events After an Acute Coronary Event Remains High, Especially During the First Year, Despite Revascularization. Revista Española de Cardiología (English Edition). 2016;69(1):11–8. DOI: 10.1016/j.rec.2015.06.015

13. Bays HE, Taub PR, Epstein E, Michos ED, Ferraro RA, Bailey AL et al. Ten things to know about ten cardiovascular disease risk factors. American Journal of Preventive Cardiology. 2021;5:100149. DOI: 10.1016/j.ajpc.2021.100149

14. Rouland A, Masson D, Lagrost L, Vergès B, Gautier T, Bouillet B. Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review. Cardiovascular Diabetology. 2022;21(1):272. DOI: 10.1186/s12933-022-01703-5

15. Sun Y, Zhang J, Guo F, Zhao W, Zhan Y, Liu C et al. Identification of Apolipoprotein C-I Peptides as a Potential Biomarker and its Biological Roles in Breast Cancer. Medical Science Monitor. 2016;22:1152–60. DOI: 10.12659/MSM.896531

16. Yi J, Ren L, Wu J, Li W, Zheng X, Du G et al. Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer. Annals of Translational Medicine. 2019;7(16):380. DOI: 10.21037/atm.2019.07.59

17. Shi X, Wang J, Dai S, Qin L, Zhou J, Chen Y. Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer. Onco‑ Targets and Therapy. 2020;13:12881–91. DOI: 10.2147/OTT.S280690

18. Cui Y, Miao C, Hou C, Wang Z, Liu B. Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma. Frontiers in Oncology. 2020;10:1436. DOI: 10.3389/fonc.2020.01436

19. Hu Y, Meuret C, Martinez A, Yassine HN, Nedelkov D. Distinct patterns of apolipoprotein C-I, C-II, and C-III isoforms are associated with markers of Alzheimer’s disease. Journal of Lipid Research. 2021;62:100014. DOI: 10.1194/jlr.RA120000919

20. Liu B, Ahmad W, Aronson NN. Structure of the human gene for lysosomal di-N-acetylchitobiase. Glycobiology. 1999;9(6):589–93. DOI: 10.1093/glycob/9.6.589

21. Tognetti M, Sklodowski K, Müller S, Kamber D, Muntel J, Bruderer R et al. Biomarker Candidates for Tumors Identified from Deep-Profiled Plasma Stem Predominantly from the Low Abundant Area. Journal of Proteome Research. 2022;21(7):1718–35. DOI: 10.1021/acs.jproteome.2c00122

22. Kilpatrick DC, Chalmers JD. Human L-Ficolin (Ficolin-2) and Its Clinical Significance. Journal of Biomedicine and Biotechnology. 2012;2012:1–10. DOI: 10.1155/2012/138797

23. Szala A, Sawicki S, Swierzko ASt, Szemraj J, Sniadecki M, Michalski M et al. Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours. Cancer Immunology, Immunotherapy. 2013;62(8):1411–9. DOI: 10.1007/s00262-013-1445-3

24. Hu Y -L., Luo F -L., Fu J -L., Chen T -L., Wu S -M., Zhou Y -D. et al. Early Increased Ficolin-2 Concentrations are Associated with Severity of Liver Inflammation and Efficacy of anti-Viral Therapy in Chronic Hepatitis C Patients. Scandinavian Journal of Immunology. 2013;77(2):144–50. DOI: 10.1111/sji.12014

25. Jalal PJ, King BJ, Saeed A, Adedeji Y, Mason CP, Ball JK et al. Elevated serum activity of MBL and ficolin-2 as biomarkers for progression to hepatocellular carcinoma in chronic HCV infection. Virology. 2019;530:99–106. DOI: 10.1016/j.virol.2019.02.002

26. Giraudi PJ, Salvoza N, Bonazza D, Saitta C, Lombardo D, Casagranda B et al. Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences. 2022;23(5):2813. DOI: 10.3390/ijms23052813

27. Kinders R, Jones T, Root R, Bruce C, Murchison H, Corey M et al. Complement factor H or a related protein is a marker for transitional cell cancer of the bladder. Clinical Cancer Research. 1998;4(10):2511–20. PMID: 9796985

28. Cheng Z-Z, Corey MJ, Pärepalo M, Majno S, Hellwage J, Zipfel PF et al. Complement Factor H as a Marker for Detection of Bladder Cancer. Clinical Chemistry. 2005;51(5):856–63. DOI: 10.1373/clinchem.2004.042192

29. Lu G, Liu W, Huang X, Zhao Y. Complement factor H levels are decreased and correlated with serum C-reactive protein in late-onset Alzheimer’s disease. Arquivos de Neuro-Psiquiatria. 2020;78(2):76–80. DOI: 10.1590/0004-282x20190151

30. Hu WT, Watts KD, Tailor P, Nguyen TP, Howell JC, Lee RC et al. CSF complement 3 and factor H are staging biomarkers in Alzheimer’s disease. Acta Neuropathologica Communications. 2016;4(1):14. DOI: 10.1186/s40478-016-0277-8

31. Ingram G, Hakobyan S, Hirst CL, Harris CL, Pickersgill TP, Cossburn MD et al. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain. 2010;133(6):1602–11. DOI: 10.1093/brain/awq085