Hasil Pencarian  ::  Simpan CSV :: Kembali

"Polimorfisme CYP2C19 menurunkan metabolisme klopidogrel dan telah diketahui meningkatkan mortalitas serta kejadian kardiovaskular mayor. VerifyNow P2Y12 merupakan salah satu pemeriksaan yang secara spesifik menggambarkan fungsi platelet terhadap agen penghambat P2Y12 yang dikonsumsi. Hubungan antara polimorfisme CYP2C19 dengan TIMI flow pada populasi Asia, khususnya Indonesia, belum pernah dilakukan.Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfisme CYP2C19 terhadap fungsi penghambatan platelet dan TIMI flow, serta hubungan antara fungsi penghambatan platelet dan TIMI flow.Dilakukan pemeriksaan polimorfisme CYP2C19 dengan menggunakan metode Taqman dan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12 pada 90 pasien IMA-EST yang menjalani IKPP yang memenuhi kriteria penelitian.Dari 90 subyek penelitian, studi polimorfisme genetik mengungkapkan 23,3% pasien dengan alel * 2, 11,2% dari * 3 alel pembawa, dan 1,1% membawa kedua alel. 24,4% pasien tergolong non-responder terhadap klopidogrel. Secara keseluruhan tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow 3, namun terdapat hubungan antara polimorfisme CYP2C19 dengan penurunan fungsi penghambatan platelet (OR 4.7, p = 0.030). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.046).Tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow, namun pasien dengan polimorfisme CYP2C19*2 dan/atau *3 memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet. Pasien yang tergolong non-responder terhadap klopidogrel ini juga berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

---

CYP2C19 polymorphism plays an important role in clopidogrel metabolism. The genetic factor is VerifyNow P2Y12 is an examination that specifically describes platelet function against P2Y12 inhibitors. It is unknown whether platelet reactivity measured by P2Y12 reaction unit (PRU) is affected by CYP2C19 polymorphism or predictive of TIMI flow in Asian populations, particularly in Indonesia. We sought to define whether polymorphisms on CYP2C19 genes and platelet reactivity may affect the myocardial perfusion.

STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Genetic polymorphisms analysis to assess the presence of CYP2C19*2 and *3 alleles on each patient were performed by Taqman method.

There were 90 patients recruited for study. Genetic polymorphisms studies revealed 23.3% of patients with *2 allele, 11.2% of *3 allele carriers, and 1.1% carried both allele. 23.4% of patients were clopidogrel non-responders. Overall, there was no correlation between CYP2C19 polymorphism and TIMI flow < 3, but there was a relationship between CYP2C19 polymorphism and decreased function of platelet inhibition (OR 4.7, p = 0.030). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.046).

There is no direct relationship between CYP2C19 polymorphism and TIMI flow, but patients with CYP2C19*2 and/or CYP2C19*3 had increased risk of being clopidogrel non responders. After adjusted to confounding factors, VerifyNow > 208 PRU is associated with suboptimal myocardial reperfusion."

"Latar belakang: micro-RNA saat ini telah diketahui berperan dalam patofisiologi berbagai penyakit termasuk di bidang kardiovaskular. miR-26a platelet dikaitkan dengan aktifitas platelet tinggi.Resistensi klopidogrel telah diketahui memiliki prevalensi yang cukup tinggi di populasi Asia, yang mana dapat mempengaruhi mortalitas serta kejadian kardiovaskular mayor. Hubungan antara ekspresi miR-26a platelet dengan resistensi klopidogrel begitu pula dengan TIMI flow pasca IKPP pada IMA-EST di populasi Asia, belum pernah dilaporkan. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi miR-26a platelet terhadap reaktivitas platelet dan perfusi miokardium pasca IKPP. Metode: Pada pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi dosis loadingklopidogrel 600 mg, dimasukkan kedalam populasi penelitian. Kami mengukur reaktivitas platelet dengan menggunakan VerifyNow P2Y12, aktifitas platelet tinggi didefiniskan jika memiliki nilai > 208 PRU. Metode RealtimePCR Taqman dilakukan untuk analisa ekspresi miR-26a platelet. Ekspresi miR-26a platelet dan reaktivitas platelet dikorelasikan dengan TIMI flowpasca IKPP pada pasien IMA-EST. Hasil: Terdapat 100 subyek yang direkrut pada studi ini. Diantaranya, 59% menunjukkan peningkatan ekspresi miR-26a. Reaktifitas platelet meningkat pada 27 % pasien studi ini dikategorikan non-responder terhadap klopidogrel. Terdapat hubungan antara ekspresi dengan penurunan fungsi penghambatan platelet (OR 4.2, p = 0.006). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.015). Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIMI flow < 3. Kesimpulan: Pasien dengan peningkatan ekspresi miR-26a platelet memiliki risiko untuk mengalami menjadi non-responderklopidogrel. Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIM flowpasca IKPP.

---

Background: micro-RNA has now been known to play a role in the pathophysiology of various diseases including cardiovascular disease. Clopidogrel resistance has been known prevalent in Asian population, that may affect mortality and major cardiovascular events. The relationship between the expression of platelet miR-26a and clopidogrel resistance as well as TIMI flow post primary PCI in STEMI among Asian populations, has never been done.

Objective: the aim of this study is to define whether miR-26a platelet expression has a relation with platelet reactivity and myocardial perfusion after primary PCI.

Methods: STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Realtime PCR by taqman method were performed to asses the expression of miR-26a platelet. miRNA-26a platelet expression and platelet reactivity were correlated with TIMI flow post primary PCI in STEMI.

Hasil: there were 100 patients recruited for this study. among them, 59% of patients with high expression of miR-26a platelet. Platelet reactivity showed 27% of the patients were clopidogrel non-responders. There was a relationship between high miR-26a expression and decreased function of platelet inhibition (OR 4.2, p = 0.006). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.015). There was no direct correlation between miR-26a expression and TIMI flow < 3.

Conclusion: Patients with high miR-26a platelet expression had increased risk of being clopidogrel non responders. There is no direct relationship between miR-26a platelet expression and TIMI flow after primary PCI."

"ABSTRAKLatar belakang: Salah satu faktor yang dicurigai berperan dalam mekanisme resisensi klopidogrel adalah faktor epigenetik seperti metilasi DNA. Individu dengan resistensi klopidogrel ini memiliki kecenderungan untuk mengalami luaran kardiovaskular yang lebih buruk. Nilai TIMI flow pasca IKPP telah diketahui berkaitan dengan luaran klinis pada pasien IMA-EST. Sampai saat ini belum ada penelitian yang menghubungan antara metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Tujuan: Untuk mengetahui hubungan antara metilasi gen reseptor P2Y12 terhadap fungsi penghambatan platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Metode: Sebanyak 118 pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi klopidogrel dimasukkan kedalam populasi penelitian. Dilakukan pemeriksaan VerifyNow P2Y12 dan pemeriksaan metilasi P2Y12. Selanjutnya dilakukan analisis hubungan antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Hasil: Dari seluruh subyek, 22% diantaranya termasuk klopidogrel nonresponder dan 30% memiliki nilai TIMI flow kurang dari 3. Terdapat 48% subyek yang tidak mengalami metilasi dan 19% subyek mengalami metilasi sempurna pada gen P2Y12. Tidak terdapat hubungan bermakna antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Nilai Verifynow P2Y12 yang tinggi berhubungan dengan TIMI flow kurang dari 3 pasca IKPP (p=0,043). Kesimpulan: Tidak terdapat hubungan bermakna antara pola metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP. Pasien yangnon-responder terhadap klopidogrel berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

---

ABSTRACTBackground: Mechanism of clopidogrel resistance is not well understood yet. In the other hand, epigenetic modifications such as DNA methylation, are suspected to play role in clopidogrel resistence. Subject with high on treatment clopidogrel reactivity show worsen cardiovascular outcome. Meanwhile, TIMI flow after reperfusion are known to be related with poor outcome. Study that evaluate the relationship between methylation of P2Y12 gene with Platelet Reactivity and TIMI-flow after Primary Percutaneous Coronary Intervention (PPCI) in Patients With Acute ST-segment Elevation Myocardial Infarction in South East Asia Population has never been done. Objectives: to define whether methylation of P2Y12 gene and platelet reactivity may affect the myocardial perfusion after PPCI. Methods: There were 118 of STEMI patients who underwent PPCI and had received clopidogrel were recruited for the study. We measured platelet reactivity using Verifynow P2Y12 and Methylation of P2Y12 gene. The relationship among variables are assessed using statistic method. Results: Among 118 subject, 22% are clopidogrel nonresponder and 30% had TIMI flow less than 3. Median of Methylation degree was 15% with 48% subject were unmethylated, 19% subject had 100% methylation. There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. The value of Verifynow P2Y12 more than 208 were related TIMI flow less than 3 after PPCI (p=0,043). Conclusion: There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. Clopidogel nonresponder subjects were more likely to have suboptimal reperfusion after PPCI"