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 MMP2, MMP9 and their inhibitors TIMP1 and TIMP2 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 (nâ¯= 42.5%), respiratory failure (nâ¯= 10.8%) and sepsis (nâ¯= 6.7%). Blood samples were taken within 12â¯h of ICU admission. The MMP2, MMP9, TIMP1 and TIMP2 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 MMP9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10-2.53; pâ¯= 0.016) and TIMP1 (OR 2.15 per 1 SD; 95% CI 1.27-3.64; pâ¯= 0.004) levels than non-survivors; furthermore, MMP9 and TIMP1 correlated well with SAPS II (both pâ¯< 0.01). In patients with underlying cardiac diseases, MMP9 (pâ¯= 0.002) and TIMP1 (pâ¯= 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP2 and TIMP2 levels, MMP/TIMP ratios and 30-day mortality. CONCLUSION: The MMP9 and TIMP1 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.