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January 18, 2018Työväentutkimus Vuosikirja68 citationsOpen Access

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

LLLaura LahdentaustaJLJaakko LeskeläAWAlina Winkelmann

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.

Key Points

  • The study aims to explore the role of MMP-9 and its inhibitor TIMP-1 in acute coronary syndrome and its recurrence.
  • Age- and gender-matched case-control study with N=669 ACS patients.
  • Follow-up over 6 years with resampling after recovery (45.7% of patients).
  • MMP-9 levels analyzed using gelatin zymography.
  • MMP-9 and MMP-9/TIMP-1 ratio significantly associated with ACS (OR 5.81, 95% CI 2.65-12.76; OR 4.96, 95% CI 2.37-10.38).
  • MMP-9 concentrations decreased by 49% during recovery (p < 0.001).
  • High in vitro activatable MMP-9 levels linked to fatal cardiac events (p = 0.028).

Study Design

Type

Case-Control (n=669)

Multicenter

No

Structured PICO

P
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.
O
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
  • Cannot estimate the proportion of MMP-9 excreted from ischemic myocardium or ruptured atherosclerotic plaques from serum analysis.
  • No information on the infarct size; thus, the models cannot be adjusted by it.
  • In zymography analysis, cannot calculate the total physiological MMP-9 activity.
  • Serum samples were collected in 1999–2002, when the use of statins was not common.
  • Could not adjust the models with BMI and blood pressure, as this information was not available for 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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Cite This Study

Lahdentausta et al. (2018) conducted a case-control in Acute Coronary Syndrome (n=669). Elevated serum MMP-9 vs. Controls without coronary heart disease was evaluated on Association with Acute Coronary Syndrome (ACS) (OR 5.81, 95% CI 2.65-12.76, p=<0.001). 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.

synapsesocial.com/papers/6a21668b36bad5b948f1a813https://doi.org/10.1007/s12265-018-9789-x
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