Biomarkers of inflammation in patients with myocardial infarction and heart failure with preserved and mid-range ejection fraction: 5-year prospective follow-up

Aim. To evaluate the effect of biomarkers of inflammation on the long-term prognosis in patients with myocardial infarction (MI) and heart failure (HF) with preserved and mid-range ejection fraction according to a registry of percutaneous coronary interventions (PCI).

Material and methods. A total of 135 patients with MI included in the PCI registry in 2012-2013 were examined. Group 1 included 89 patients with HF with mid-range ejection fraction (HFmrEF) — 40-49%; group 2 included 46 patients with HF with preserved ejection fraction (HFpEF) — ≥50%. Biomarkers of inflammation were determined at admission to the hospital, after 12 and 60 months.

Results. Eighteen people died during the follow-up period. The survival rate of patients in the compared groups after 60 months did not differ (group 1 — 85,0%; group 2 — 89,1%, p=0,492). Mortality predictors were the platelet count (HR, 1,011; 95% CI, 1,003-1,019; p=0,010), homocysteine level (HR 1,172; 95% CI, 1,008-1,364; p=0,040), MMP-9 >249 ng/ml (HR, 7,052; 95% CI, 1,346-36,950; p=0,021). In both groups there was a decrease in survival in patients with high levels of MMP-9 (>249 ng/ml). In group 1, mortality was higher among patients with platelet count >245*10⁹/l. In both groups the levels of inflammatory markers exceeded the standard values for the entire period of follow-up. The dynamics of NT-proBNP, hs-CRP, TNF-α and homocysteine had a unidirectional pattern, in particular, a decrease in parameters after 12 months, followed by their increase after 60 months.

Conclusion. Levels of MMP-9, homocysteine, and platelets were the factors that influenced 5-year survival in the general group of patients after MI and PCI. In the group with HFmrEF, MMP-9 and platelets had a negative impact on the prognosis. In patients with HFpEF, reduced survival was associated only with high levels of MMP-9. The dynamics of markers of systemic inflammatory response and NT-proBNP indicates the prolonged inflammatory process in both groups of patients, persisting for 5 years after MI.

1. Ponikowski P, Voors AA, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2016;37(27):2129-200. doi:10.1093/eurheartj/ehw128.

2. Rajendiran KS. Elevated levels of serum sialic acid and high-sensitivity C-reactive protein: markers of systemic inflammation in patients with chronic heart failure. Br J Biomed Sci. 2014;71(1):29-32. doi:10.1080/09674845.2014.11669959.

3. Nikiforova TA, Shchekochikhin DYu, Kopylov FYu, et al. Prognostic value of biomarkers in chronic heart failure with preserved left ventricular ejection fraction. Therapeutic archive. 2016;9:102-5. (In Russ.) doi:10.17116/terarkh2016889102-105.

4. Tokmachev RE Participation of cytokines in the development of heart failure. Young scientist. 2015;3(83):296-8. https://moluch.ru/archive/83/15046. (In Russ.) https://moluch.ru/archive/83/15046.

5. Medvedeva EA, Surkova EA, Lymareva LV, et al. Molecular biomarkers in the diagnosis, risk stratification, and prediction of chronic heart failure. Russian Journal of Cardiology. 2016;(8):86-91. (In Russ.) doi:10/15829/1560-4071-2016-8-86-91.

6. Pecherina TB, Barbarash OL. Clinical and prognostic value of matrix metalloproteinases in patients with myocardial infarction. Fundamental and clinical medicine. 2019;4(2):84-94. (In Russ.) doi:10.23946/2500-0764-2019-4-2-84-94.

7. Zhu JJ, Zhao Q, Qu HJ, et al. Usefulness of plasma matrix metalloproteinase-9 levels in prediction of in-hospital mortality in patients who received emergent percutaneous coronary artery intervention following myocardial infarction. Oncotarget. 2017;8(62):105809-18. doi:10.18632/oncotarget.22401.

8. Fu Z, Qian G, Xue H, et al. Hyperhomocysteinemia is an independent predictor of longterm clinical outcomes in Chinese octogenarians with acute coronary syndrome. Clin Interv Aging. 2015;10:1467-74. doi:10.2147/CIA.S91652.

9. Davidchek EV, Snezitckyi VA, Niconova LV. Relationship of hyperhomocysteinemia with coronary heart disease and Diabetes mellitus. Education Establishment Grodno State Medical University. 2015;1:9-13. (In Russ.)

10. Duchene J, von Hundelshausen P. Platelet-derived chemokines in atherosclerosis. Hamostaseologie. 2015;35(2):137-41. doi:10.5482/HAMO-14-11-0058.

11. Mazurov AV. Turnover of platelets and atherothrombosis. Atherothrombosis. 2017;(2):131-141. (In Russ.) doi:10.21518/2307-1109-2017-2-131-141.

12. Buryachkovskaya LI, Uchitel IA, Sumarokov AB, et al. The multi-functionality of platelets, their activation and possibilities of its evaluation. Cardiovascular diseases Bulletin of the Bakulev research center of the Russian Academy of medical Sciences. 2007;8(2):43-50. (In Russ.)

13. Serneri GG, Boddi M, Cecioni I, et al. Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function. Cir. Res. 2001;88(9):961-8. doi:10.1161/hh0901.089882.

14. Petelina TI, Musikhina NA, Gapon LI, et al. Prospective analysis of lipid spectrum parameters and markers of inflammatory vascular response with prediction of adverse coronary events in patients with coronary heart disease after angioplasty with stenting. Clinical laboratory diagnostics. 2018;63(8):471-7. (In Russ.) doi:10.18821/0869-2084-2018-63-8-471-477.