Effect of therapy on the dynamics of collagen metabolism markers in older patients with heart failure with mid-range ejection fraction and coronary artery disease

Abstract

Aim. To assess the dynamics of collagen metabolism markers during. Material and methods. This open-label, controlled, age-randomized therapy in older patients with heart failure with mid-range ejection study included 162 patients with HFmrEF. Group 1 consisted of 82 fraction (HFmrEF) and coronary artery disease. elderly patients (mean age, 68±5 years), group 2 — 80 elderly senile patients (mean age, 79±3 years). The levels of matrix metalloproteina-ses (MMP-1, MMP-9) and tissue inhibitor of metalloproteinases (TIMP-1) were determined by enzyme-linked immunosorbent assay using test systems MMP-1 ELISA, MMP-9 ELISA, and Human TIMP-1 ELISA, respectively. Results. In elderly subjects taking bisoprolol, there was a decrease in collagen metabolism markers as follows: MMP-9 — by 43% (p<0,001), MMP-1 — ∆32%, TIMP-1 — ∆20% (p<0,01); nebivolol: MMP-9 — ∆50% (p<0,001), MMP-1 — ∆39%, TIMP-1 — ∆2% (p<0,01). Combined therapy with bisoprolol and eplerenone reduced the levels of MMP-9 by 52%, MMP-1 by 43% (p<0,001), and TIMP-1 by ∆32% (p<0,01), while combination of nebivolol and eplerenone decreased MMP-1 by 46%, MMP-9 by ∆59%, and TIMP-1 by ∆40% (p<0,001). In senile patients, bisoprolol decreased MMP-1 by 24%, MMP-9 by ∆39%, and TIMP-1 by ∆17% (p<0,01); nebivolol: MMP-9 — ∆46% (p<0,001), MMP-1 — ∆33%, TIMP-1 — ∆25% (p<0,01). Combined therapy with bisoprolol and eplerenone reduced the levels of MMP-1 by 40%, MMP-9 by ∆50% (p<0,001), and TIMP-1 by ∆26% (p<0,01), while combination of nebivolol and eplerenone decreased MMP-1 by 47%, MMP-9 by ∆57% (p<0,001), and TIMP-1 by ∆34% (p<0,01). Conclusion. Twelve-month therapy with p-blockers (bisoprolol, nebivolol) in older patients with HFmrEF significantly reduced the levels of collagen metabolism markers MMP-1, MMP-9, and TIMP-1. The maximum effect was observed in the nebivolol+eplerenone group.