Perbedaan Rasio Kadar Serum MMP-9/TIMP- 1 pada Kejadian Infark Miokard Akut Elevasi Segmen ST (IMA-EST) dan Sindroma Koroner Akut Non Elevasi Segmen-ST (SKA-NEST)

Background: Differences between the pathogenesis of ST-Elevation Myocardialinfarction (STEMI) and Non-ST Elevation Acute Coronary Syndrome(NSTE-ACS) had yet unknown. Matrix metalloproteinase-9 (MMP-9) as thematrix degradation enzyme secreted by inflammatory cells play a role in thepathogenesis of plaque rupture. MMP-9 proteolytic activity is inhibited byspecific inhibitors of the Tissue Inhibitor of metalloproteinase-1 (TIMP-1).MMP-9/TIMP-1 ratio describes the actual proteolytic activity of MMP-9.This ratio may distinguish the pathogenesis of STEMI and NSTE-ACS.Objective: To examine the difference serum level ratio MMP-9/TIMP-1 inpatients with STEMI and NSTE-ACS.Methods and subjects: This is a cross-sectional study which recruits patientsconsecutively with ACS admitted to ICCU of Dr. Sardjito General Hospital Yogyakartawithin 24 h onset. Acute infection, chronic inflammation, acute stroke,kidney failure requiring renal replacement therapy, chronic heart failure, liver cirrhosis,acute exacerbation of COPD and pneumonia, thromboembolic disease,malignancy, pregnancy and the use of steroids and steroid anti-inflammatorydrugs are excluded. Serum levels of MMP-9 and TIMP-1 examined using themethod of sandwich enzyme-linked immunosorbent assay (ELISA).Results: The total of 60 subjects with STEMI patients 31 (51.7%) and NSTEACS29 (48.3%). Level of serum MMP-9/TIMP-1 ratio is significantly higher inSTEMI compared to NSTE-ACS (1.106 ± 0.065 vs. 1.046 ± 0.057, p <0.001).MMP-9/TIMP-1 ratio in serum is an independent factor for STEMI (p = 0.003)followed by blood sugar level (p = 0.013) and MMP-9 (p = 0.033). Interestingly,patients with serum MMP-9/TIMP-1 ratio> 1.0639 has a prevalence riskof 1.7 times having STEMI (p = 0.039; KI95% from 1.040 to 8.508). Levels ofserum MMP-9/TIMP-1 ratio significantly higher in STEMI compared to NSTEMIgroup (p = 0.003) and in the STEMI and UAP group (0.026), but did not differsignificantly in NSTEMI and UAP group (p = 0.045).Conclusion: High levels of serum MMP-9/TIMP-1 ratio in patients withSTEMI than NSTEACS may explain the role of serum MMP-9/TIMP-1 ratioin differentiating the pathogenesis of STEMI and NSTE-ACS.(J Kardiol Indones. 2013;34:160-6)Latar Belakang: Perbedaan antara patogenesis Infark miokard akut elevasi segmen ST (IMA-EST) dan Sindroma koronerakut non elevasi segmen ST (SKA-NEST) sampai saat ini belum jelas. Matrix Metalloproteinase-9 (MMP-9) sebagai enzimdegradasi matrik yang disekresikan oleh berbagai sel inflamasi berperan dalam patogenesis ruptur plak. Aktivitas proteolitikMMP-9 dihambat oleh inhibitor spesifiknya yaitu Tissue Inhibitor Metalloproteinase-1 (TIMP-1). Rasio MMP-9/TIMP-1menggambarkan aktivitas proteolitiknya MMP-9 sebenarnya. Rasio ini mungkin membedakan patogenesis IMA-EST danSKA-NEST. Akan tetapi, sampai saat ini belum ada studi yang membandingkan rasio kadar serum MMP-9/TIMP-1 padapasien IMA-EST dan SKA-NEST.Tujuan: untuk mengetahui perbedaan rasio kadar serum MMP-9/TIMP-1 pada pasien IMA-EST dan SKA-NEST.Subjek dan metode penelitian: penelitian ini merupakan studi potong lintang dengan pengambilan sampel penelitian secarakonsekutif pada pasien sindroma koroner akut (SKA) yang dirawat di Intensive Coronary Care Unit (ICCU) dalam waktu 24jam onset. Pasien infeksi akut, inflamasi kronik, stroke akut, gagal ginjal yang membutuhkan terapi pengganti ginjal, gagaljantung kronik, sirosis hepatis, PPOK eksaserbasi akut dan pneumonia, penyakit tromboemboli, keganasan, kehamilan danpenggunaan steroid dan obat anti inflamasi bukan steroid dieksklusi. Kadar serum MMP-9 dan TIMP-1 diperiksa denganmetode sandwich enzyme-linked immunosorbent assay (ELISA).Hasil: Total subjek penelitian sebanyak 60 pasien SKA dengan IMA-EST 31 (51,7%) dan SKA-NEST 29 (48,3%). Rasiokadar serum MMP-9/TIMP-1 lebih tinggi bermakna pada IMA-EST dibandingkan SKA-NEST (1,106±0,065 vs 1,046±0,057;p<0,001). Rasio kadar serum MMP-9/TIMP-1 merupakan faktor independen untuk IMA-EST (p=0,003) diikuti gula darahsewaktu (p=0,013) dan MMP-9 (p=0,033). Menariknya, pasien dengan rasio kadar serum MMP-9/TIMP-1 >1,0639 memilikirisiko prevalensi 1,7 kali terjadi IMA-EST (p=0,039;KI95% 1,040-8,508). Rasio kadar serum MMP-9/TIMP-1 lebih tinggibermakna pada kelompok IMA-EST dibandingkan IMA-NEST (p=0,003) dan pada kelompok IMA-EST dan Angina pektoristidak stabil (APTS) (0,026), tapi tidak berbeda bermakna pada kelompok IMA-NEST dan APTS (p=0,045).Kesimpulan: Tingginya rasio kadar serum MMP-9/TIMP-1 pada pasien IMA-EST dibandingkan SKA-NEST mungkinmenjelaskan peran rasio kadar serum MMP-9/TIMP-1 dalam membedakan patogenesis IMA-EST dan SKA-NEST.(J Kardiol Indones. 2012;33:160-6