What is the clinical evidence from this study?

Study design: Case-Control. Population: Acute Coronary Syndrome (n=669). Intervention: Elevated serum MMP-9 vs. Controls without coronary heart disease. Primary outcome: Association with Acute Coronary Syndrome (ACS) (OR 5.81, 95% CI 2.65-12.76, p=<0.001).

January 18, 2018Open Access

Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome and Its Recurrence

Q: What are the key findings of this study?

Elevated serum MMP-9 concentrations were strongly associated with acute coronary syndrome (OR 5.81) and high acute phase levels predicted fatal major adverse cardiac events.

Key Result

Elevated serum MMP-9 concentrations were strongly associated with acute coronary syndrome (OR 5.81) and high acute phase levels predicted fatal major adverse cardiac events.

Study Design

Type

Case-Control (n=669)

Multicenter

Structured PICO

Population

669 adults under 80 years of age, comprising 343 patients with acute coronary syndrome and 326 matched controls, followed for an average of 6 years.

Outcome

Major adverse cardiac event (MACE), defined as cardiovascular death or hospitalization for an ACS event, during an average 6-year follow-up, and the diagnostic association of MMP-9 and MMP-9/TIMP-1 molar ratio with ACS.hard clinical

Serum MMP-9 and the MMP-9/TIMP-1 molar ratio are elevated in acute coronary syndrome, and their activation potential is associated with fatal cardiovascular outcomes, suggesting value as diagnostic and prognostic biomarkers.

Main Result

Odds Ratio: 5.81 (95% CI 2.65–12.76)

p-value: p=<0.001

Limitations

Cannot estimate the proportion of MMP-9 excreted from ischemic myocardium or ruptured atherosclerotic plaques from serum analysis
No information on infarct size to adjust models
Cannot calculate total physiological MMP-9 activity in zymography analysis
Samples collected in 1999-2002 when statin use was not common
Could not adjust models for BMI and blood pressure due to lack of data in the control population

Abstract

Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important in acute coronary syndrome (ACS). This is an age- and gender-matched case-control study of ACS (N = 669). Patients (45.7%) were resampled after recovery, and all were followed up for 6 years. The molecular forms of MMP-9 were investigated by gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were associated with ACS (OR 5.81, 95% CI 2.65-12.76, and 4.96, 2.37-10.38). The MMP-9 concentrations decreased 49% during recovery (p < 0.001). The largest decrease of these biomarkers between acute and recovery phase (ΔMMP-9) protected the patients from major adverse cardiac events, especially the non-fatal events. The fatal events were associated with in vitro activatable MMP-9 levels (p = 0.028). Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and prognosis. High serum MMP-9 activation potential is associated with poor cardiovascular outcome.

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