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Published on: January 28, 2020
Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome
Onkar S Dhillon1, Sohail Q Khan, Hafid K Narayan
1Department of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK. dhillonos@hotmail.com
Abstract:
The aim of the present study was to investigate the predictive value of MMP (matrix metalloproteinase)-2, MMP-3 and MMP-9 levels in patients with acute coronary syndrome for death, readmission with HF (heart failure) or recurrent MI (myocardial infarction) and to compare them with established markers, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the GRACE (Global Registry of Acute Coronary Events) score. A single blood test was taken 4 days after admission in 1024 consecutive patients with acute MI with end points observed over 519 (134-1059) days [value is median (range)]. MMP-2 and MMP-3 were increased in patients who died (n=111) compared with survivors (P<0.006 and P=0.01 respectively), but were similar in patients with HF (n=106) or MI (n=138). MMP-9 levels were similar across study end points. Using Cox proportional hazards modelling, MMP-2 demonstrated an independent prediction of death [HR (hazard ratio) 6.60, P=0.001], along with NT-proBNP (HR 4.62, P<0.001) and the GRACE score (HR 1.03, P<0.001), but MMP-3, MMP-9 or log10-troponin I did not. For 1 year mortality, the areas under the receiver operating characteristic curves were 0.60 and 0.58 for MMP-2 and MMP-3 respectively, compared with 0.82 for NT-proBNP and 0.84 for the GRACE score (all P<0.001). Kaplan-Meier analysis revealed that MMP-2 levels in the top quartile were associated with higher mortality rates (log rank 12.49, P=0.006). On univariate analysis, MMP-2 and MMP-3 had a weak association with HF readmission, which was lost after adjustment for clinical factors. None of the MMPs tested predicted MI. In conclusion, this is the first single centre study that identifies MMP2 as an independent predictor of all-cause mortality post-ACS (acute coronary syndrome); however, NT-proBNP and the GRACE score are superior for risk stratification in this cohort.
Insights
Matrix metalloproteinase-2 (MMP-2) independently predicts death after acute coronary syndrome (ACS). However, N-terminal pro-B-type natriuretic peptide and the GRACE score offer superior risk stratification for patients with ACS.
Area of Science:
- Cardiology
- Biomarker Research
- Acute Coronary Syndromes
Background:
- Acute coronary syndrome (ACS) poses significant mortality risks.
- Established risk stratification tools include NT-proBNP and the GRACE score.
- The predictive value of matrix metalloproteinases (MMPs) in ACS requires further investigation.
Purpose of the Study:
- To assess the predictive value of MMP-2, MMP-3, and MMP-9 levels for mortality, heart failure (HF) readmission, and recurrent myocardial infarction (MI) in ACS patients.
- To compare the predictive performance of MMPs with NT-proBNP and the GRACE score.
Main Methods:
- A cohort of 1024 consecutive patients with acute MI was studied.
- Blood samples were collected 4 days post-admission for MMP-2, MMP-3, MMP-9, and troponin I analysis.
- End points (death, HF readmission, recurrent MI) were observed over a median of 519 days.
- Cox proportional hazards modeling and receiver operating characteristic (ROC) curve analysis were employed.
Main Results:
- MMP-2 and MMP-3 levels were elevated in non-survivors compared to survivors.
- MMP-2 independently predicted all-cause mortality (HR 6.60, P=0.001).
- NT-proBNP and the GRACE score demonstrated superior 1-year mortality prediction (AUC 0.82 and 0.84) compared to MMP-2 (AUC 0.60) and MMP-3 (AUC 0.58).
- MMP levels did not predict HF readmission or recurrent MI.
Conclusions:
- MMP-2 is identified as an independent predictor of all-cause mortality post-ACS.
- NT-proBNP and the GRACE score remain superior for risk stratification in ACS patients.
- Further research may explore MMPs in conjunction with established markers for comprehensive risk assessment.
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