Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome.
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.
Dhillon
Onkar S
OS
Department of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK. dhillonos@hotmail.com
Khan
Sohail Q
SQ
Narayan
Hafid K
HK
Ng
Kelvin H
KH
Mohammed
Noor
N
Quinn
Paulene A
PA
Squire
Iain B
IB
Davies
Joan E
JE
Ng
Leong L
LL
D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests / Q000379:methods; D004739:England / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000175:diagnosis; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010359:Patient Readmission / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D012720:Severity of Illness Index; D016019:Survival Analysis; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000000981:diagnostic imaging
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9