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. 2021 Feb;133(3-4):86-95.
doi: 10.1007/s00508-019-01592-x. Epub 2020 Jan 13.

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival

Galateja Jordakieva  1 , Roswitha M Budge-Wolfram  2   3 , Alexandra C Budinsky  4 , Mariam Nikfardjam  5 , Georg Delle-Karth  6 , Angelika Girard  4 , Jasminka Godnic-Cvar  1 , Richard Crevenna  1 , Gottfried Heinz  7
Affiliations

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival

Galateja Jordakieva et al. Wien Klin Wochenschr. 2021 Feb.

Abstract

Background: Matrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP‑2, MMP‑9 and their inhibitors TIMP‑1 and TIMP‑2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU).

Methods: In a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the ICU of a cardiology department. The most common underlying conditions were cardiac diseases (n = 42.5%), respiratory failure (n = 10.8%) and sepsis (n = 6.7%). Blood samples were taken within 12 h of ICU admission. The MMP‑2, MMP‑9, TIMP‑1 and TIMP‑2 levels in plasma were evaluated in terms of 30-day survival, underlying condition and clinical score.

Results: On ICU admission 30-day survivors had significantly lower plasma MMP‑9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10-2.53; p = 0.016) and TIMP‑1 (OR 2.15 per 1 SD; 95% CI 1.27-3.64; p = 0.004) levels than non-survivors; furthermore, MMP‑9 and TIMP‑1 correlated well with SAPS II (both p < 0.01). In patients with underlying cardiac diseases, MMP‑9 (p = 0.002) and TIMP‑1 (p = 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP‑2 and TIMP‑2 levels, MMP/TIMP ratios and 30-day mortality.

Conclusion: The MMP‑9 and TIMP‑1 levels are significantly elevated in acute critical care settings with increased short-term mortality risk, especially in patients with underlying heart disease. These findings support the value of MMPs and TIMPs as prognostic markers and potential therapeutic targets in conditions leading to systemic inflammation and acute organ failure.

Keywords: Critically ill patients; Matrix metalloproteinases; SAPS II; Survival; Tissue inhibitors of matrix metalloproteinases.

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Conflict of interest statement

G. Jordakieva, R.M. Budge-Wolfram, A.C. Budinsky, M. Nikfardjam, G. Delle-Karth, A. Girard, J. Godnic-Cvar, R. Crevenna and G. Heinz declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Correlation of MMP‑9 plasma levels with white blood cell count (p < 0.001)
Fig. 2
Fig. 2
Kaplan-Meier survival estimates for TIMP‑1 (a)and MMP‑9 (b). Any cause 30-day ICU mortality according to TIMP‑1 and MMP‑9 plasma level quartiles
See this image and copyright information in PMC

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