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"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.

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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.

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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."

"Latar belakang: Hubungan antara kadar gula darah yang tinggi dan thrombolysisin myocardial infarction TIMI flow pra/pascaprosedur angioplasti primerterhadap mortalitas 1 tahun belum banyak dieksplorasi.Tujuan: Penelitian ini bertujuan untuk menentukan hubungan kadar gula darahsaat admisi dan TIMI flow pra/pascaprosedur terhadap mortalitas 1 tahun pasieninfark miokard akut disertai elevasi segmen ST IMA-EST yang menjalaniintervensi koroner perkutan primer IKPP .Metode: 856 pasien IMA-EST yang dilakukan IKPP pada Januari 2014 hinggaJuli 2016 dianalisis secara retrospektif. Cut-off yang digunakan untuk kadar guladarah tinggi pada studi ini adalah ge;169 mg/dL. Kesintasan 1 tahun dinilai denganmetode Kaplan-Meier.Hasil: Pasien dengan kadar gula darah ge;169 mg/L N=307 mempunyai proporsiTIMI flow akhir 0 ndash; 1 yang lebih tinggi [3.3 vs. 0.5 ; adjusted odds ratio OR = 5.58, 95 confidence interval CI 1.30 ndash;23.9; p=0.02] dan mortalitas 1 tahun lebih tinggi [16.3 vs. 6 ; adjusted hazard ratio HR = 1.9, 95 CI1.12 ndash;3.23, p=0.017] dibanding pasien dengan kadar gula darah rendah N=549 .TIMI flow akhir 0 ndash; 1 merupakan prediktor independen mortalitas 1 tahun HR= 7.0, 95 CI 3.23 ndash;15.15;

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Background The association of high blood glucose level and Thrombolysis InMyocardial Infarction TIMI flow before after primary angioplasty with 1 yearmortality has not much been explored.Objective This study sought to determine the association of blood glucose level BGL on admission and pre post procedural TIMI flow with 1 year mortality inpatients with ST segment elevation myocardial infarction STEMI undergoingprimary percutaneous coronary intervention PCI .Methods 856 patients with STEMI and treated with primary PCI betweenJanuary 2014 and July 2016 were retrospectively analyzed. The cut off used for ahigh BGL in this study was ge 169 mg dL. Survival at 1 year was assessed byKaplan Meier method.Results Patients with BGL ge 169 mg dL N 307 had higher proportion of finalTIMI flow 0 1 3.3 vs. 0.5 adjusted odds ratio OR 5.58, 95 confidenceinterval CI 1.30 to 23.9 p 0.02 and higher 1 year mortality 16.3 vs. 6 adjusted hazard ratio HR 1.9, 95 CI 1.12 to 3.23, p 0.017 compared withlower BGL patients N 549 . Final TIMI flow 0 1 was an independent predictorof 1 year mortality HR 7.0, 95 CI 3.23 to 15.15 p"

"Pendahuluan: Intervensi koroner perkutan primer (IKPP) telah menjadi salah satu pilihan terapi pada pasien dengan infark miokard akut dengan elevasi segmen ST (IMA-EST) yang dapat menurunkan angka kematian dengan signifikan. Sebagian pasien yang menjalani IKPP mengalami kegagalan reperfusi optimal yang disebut sebagai no-reflow phenomenon (NRP). Penilaian NRP ini dapat menggunakan berbagai metode, salah satunya dengan menggunakan thrombolysis in myocardial infarction flow (TIMI flow). Kegagalan reperfusi juga meningkatkan kejadian major adverse cardiac event (MACE) pada pasien. Hiperaktivitas trombosit diketahui berperan pada patofisiologi terjadinya NRP. Nilai mean platelet volume (MPV) yang merupakan ukuran rerata volume dari trombosit dianggap dapat menggambarkan aktivasi trombosit. Penelitian ini bertujuan untuk mengetahui peran nilai MPV dengan TIMI-flow dan MACE pada pasien IMA-EST yang menjalani IKPP.Metode: Penelitian kohort retrospektif dilakukan terhadap 137 subyek dengan IMA-EST yang menjalani IKPP. Pemeriksaan MPV dilakukan pada saat masuk rumah sakit dengan alat Sysmex XN-2000. Subyek dibagi berdasarkan kelompok dengan reperfusi sub-optimal (TIMI flow < 3) dan reperfusi optimal (TIMI flow 3). Luaran klinis berupa MACE dilakukan observasi selama minimal 90 hari pasca tindakan.Hasil: Sebanyak 27.7% dan 28.9% pasien mengalami kegagalan reperfusi dan MACE. Tidak terdapat hubungan antara nilai MPV pada saat masuk rumah sakit dengan kegagalan reperfusi dan kejadian MACE 90 hari pada pasien IMA-EST di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita.Kesimpulan: Nilai MPV tidak dapat digunakan dalam memprediksi kegagalan reperfusi dan kejadian MACE pada pasien IMA-EST yang menjalani IKPP.

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Introduction: Primary percutaneous coronary intervention (PCI) has become one of the treatment options in patients with acute myocardial infarction with ST segment elevation (STEMI) which can significantly reduce mortality. In some patients who undergo primary PCI experience failure of optimal reperfusion called the no-reflow phenomenon (NRP). NRP assessment can use various methods, one of them using thrombolysis in myocardial infarction flow (TIMI flow). Failure of reperfusion also increases the incidence of major adverse cardiac events (MACE) in patients. Platelet hyperactivity is known to play a role in the pathophysiology of NRP. The mean platelet volume (MPV) which is a measure of the average volume of platelets is considered to be able to describe platelet activation. This study aims to determine the role of MPV values ​​with TIMI-flow and MACE in STEMI patients undergoing primary PCI.Methods: A retrospective cohort study was conducted on 137 STEMI patients who underwent primary PCI. MPV examination is performed at hospital admission with Sysmex XN-2000. Subjects were divided into groups with sub-optimal reperfusion (TIMI flow <3) and optimal reperfusion (TIMI flow 3). Clinical outcomes in the form of MACE were observed for at least 90 days post-treatment.Result: 27.7% and 28.9% of patients experienced failure of reperfusion and MACE, respectively. There is no relationship between the MPV value at hospital admission with failure of reperfusion and the incidence of 90-day MACE in IMA-EST patients at the Harapan Kita Heart and Vascular Hospital.Conclusion: MPV values ​​cannot be used in predicting reperfusion failure and MACE events in STEMI patients undergoing 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.

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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"

"Latar belakang: Polimorfisme Gly972Arg pada gen IRS1 dapat mengganggufungsi normal endotel dan menyebabkan disfungsi endotel. TIMI flow pascaprosedur IKPP dan jumlah pembuluh darah yang terlibat pada pasien IMA-ESTmerupakan prediktor mortalitas dan morbiditas selama perawatan. Mekanismeyang menyebabkan adanya perbedaan profil angiografi ini salah satunyadipengaruhi oleh difungsi endotel di tingkat mikrovaskular dan makrovaskular.Penelitian mengenai hubungan antara polimorfisme Gly972Arg pada gen IRS1dengan TIMI flow pasca prosedur dan jumlah keterlibatan pembuluh darah belumpernah dilakukan.Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfismeGly972Arg pada IRS1 dengan TIMI flow pasca IKPP dan jumlah keterlibatanpembuluh darah pada pasien IMA-EST.Metode: Studi potong lintang pada 104 pasien IMA-EST RSJPDHK yangmenjalani IKPP yang masuk pada registri 2018. Pemeriksaan polimorfismeGly972Arg pada IRS1 dengan menggunakan metode Taqman.Hasil: Terdapat 104 subjek yang diikutsertakan dalam penelitian ini. Subjek dibagidalam 3 kelompok, yakni grup wildtype/CC (42,3%), heterozigot/CT (49,0%), danhomozigot mutan/TT (8,7%). Tidak terdapat hubungan yang bermakna antarakelompok mutan (TT) dengan TIMI flow pasca IKPP (OR 0,8; p = 1,000) danjumlah keterlibatan pembuluh darah (OR 0,3; p = 0,163).Kesimpulan: Tidak terdapat hubungan antara polimorfisme Gly972Arg gen IRS1dengan TIMI flow pasca IKPP dan jumlah keterlibatan pembuluh darah pasien IMAEST.

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Background: Gly972Arg polymorphism of IRS1 gene can interfere with normalendothelial function and cause endothelial dysfunction. TIMI flow after the primarypercutaneous intervention procedure and the number of coronary vessels involvedin STEMI patients are predictors that determine mortality and morbidity duringtreatment. The mechanism that causes this difference in angiographic profile isinfluenced by endothelial dysfunction at the microvascular and macrovascularlevels. Research on the relationship between Gly972Arg polymorphisms of IRS1gene with TIMI flow post procedure and the amount of blood vessel involvementhas not been carried out.Objective: We sought to define whether Gly972Arg polymorphisms of IRS1 genemay affect TIMI flow after primary percutaneous intervention and number ofcoronary vessel involved.Methods: Cross-sectional study design of 104 STEMI patients who underwentprimary PCI at National Cardiovascular Center Harapan Kita Hospital at year 2018.Examination of Gly972Arg polymorphism on IRS1 is using the Taqman methodPCR.Results: There were 104 of STEMI patients who underwent primary PCI andrecruited for the study. The subjects then divided into 3 categories, which arewildtype/CC (42,3%), carrier/CT (49,0%) and mutant/TT (8,7%). There were nosignificant relationship between the mutant group (TT) with TIMI flow afterprimary PCI (OR 0.8; p = 1,000) and the number of coronary vessel involvement(OR 0.3; p = 0.163).Conclusion: There were no relationship between the Gly972Arg polymorphism ofIRS1 gene with TIMI flow after primary PCI and the number of coronary vesselinvolvement of STEMI patients."

"Latar belakang: Polimorfisme genetik dari reseptor P2Y12 dikatakan dapatmempengaruhi aktivasi reseptor P2Y12 atau menghambat aktivasi trombosit. Beberapapolimorfisme nukleotida tunggal dalam gen P2Y12 ditemukan dapat menyebabkanvariabilitas antarindividu dalam agregasi platelet. Telah diidentifikasi limapolimorfisme dari gen P2Y12 yaitu T744C, C34T, G52T, ins801A, dan C139T. Salahsatunya, polimorfisme C34T adalah salah satu dari polimorfisme yang dikatakan adakaitannya dengan peningkatan agregasi platelet yang dapat menunjukkan kemungkinanuntuk terjadinya modifikasi respon terapi clopidogrel. Namun hingga saat ini belumada penelitian yang menilai hubungan langsung antara polimorfisme reseptor P2Y12dengan TIMI-flow beserta faktor-faktor yang mempengaruhinya, termasuk fungsipenghambatan platelet pada pasien IMA-EST yang menjalani IKPP.Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfismenukleotida tunggal pada reseptor P2Y12 dengan TIMI flow beserta faktor-faktor yangmempengaruhinya, termasuk penghambatan fungsi platelet.Metode: Studi potong lintang pada 167 pasien IMA-EST yang menjalani IKPP.dilakukan pemeriksaan polimorfisme C34T reseptor P2Y12 dengan metode Taqmandan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12.Hasil: Dari 167 subjek penelitian, studi polimorfisme mengungkapkan proporsi pasiendengan heterozygous mutan sebanyak 34.1%, dan 1.8% pasien merupakan homozygousmutan. Sisanya adalah homozygous wildtype ditemukan sebanyak 64.1%. 25.7% pasientergolong non-responder terhadap clopidogrel. Secara keseluruhan tidak terdapathubungan secara langsung antara polimorfisme C34T dengan TIMI flow < 3, namunterdapat hubungan antara polimorfisme C34T dengan penurunan fungsi penghambatanplatelet (OR 2.17, p = 0.046).Kesimpulan: Tidak terdapat hubungan secara langsung antara polimorfisme C34Tdengan TIMI flow, namun pasien dengan polimorfisme C34T pada reseptor P2Y12memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet.

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Background: Genetic polymorphism of P2Y12 receptors is said to have affect of

P2Y12 receptor activation or inhibit platelet activation. Several single nucleotide

polymorphisms in the P2Y12 gene were found to cause variability between individuals

in platelet aggregation. Five polymorphisms have been identified from the P2Y12 gene,

namely T744C, C34T, G52T, ins801A, and C139T. One of them, C34T is one of the

polymorphisms that is said to be related to increased platelet aggregation which can

indicate the possibility for modification of the response of clopidogrel therapy. But until

now there has been no research that assesses the direct relationship between P2Y12

receptor polymorphisms and TIMI-flow along with the factors that influence it,

including the function of platelet inhibition in STEMI patients undergoing PPCI

Objective: This study aims to determine the relationship between single nucleotide

polymorphisms at P2Y12 receptors with TIMI flow along with the faktors that

influenced it, including inhibition of platelet function.

Methods: A cross-sectional study of 167 STEMI patients who underwent PPCI. C34T

polymorphism of P2Y12 receptor was evaluated by the Taqman method and the

inhibition of platelet function was measured by VerifyNow P2Y12.

Results: Among 167 subjects, the heterozygous mutants group were 34.1%, and 1.8%

of patients were homozygous mutants. The rest 64.1% was homozygous wildtype.

25.7% of patients were classified as non-responders to clopidogrel. Overall there was

no direct relationship between C34T polymorphisms and TIMI flow <3, but there was

a relationship between C34T polymorphisms and decreased platelet inhibitory function

(OR 2.17, p = 0.046).

Conclusion: There is no direct relationship between C34T polymorphisms and TIMI

flow, but patients with C34T polymorphisms of P2Y12 receptors have a risk of

decreasing platelet function inhibition."

"STEMI adalah IMA dengan risiko mortalitas tinggi. Risiko dikurangi dengan revaskularisasi berupa IKPP Gangguan kardiovaskular dikaitkan dengan penurunan konsentrasi vitamin D. Penurunan bisa disebabkan SNP gen CYP27B1 yang mengkode enzim 1α hidroksilase dan belum ada penelitian yang menghubungkan konsentrasi vitamin D pada pasien STEMI yang menjalani IKPP. Hasil IKPP berupa area sumbatan dan kemampuan darah mengalir ke pembuluh darah koroner, dikenal dengan TIMI grade 0-3. Penelitian bertujuan untuk menganalisis hubungan konsentrasi kalsidiol dan gen CYP27B1 (-rs10877012) perubahan G ke T pada pasien STEMI yang menjalani IKPP dengan aliran TIMI akhir. Seratus subjek STEMI dan kontrol diambil 3 mL darah. Plasmanya diukur konsentrasi kalsidiol dengan teknik ELISA. PBMC dianalisis gen CYP27B1 (- rs10877012) dengan qRT PCR teknik Taqman Probe. Data dianalisis statistik kemaknaan 0,05. Konsentrasi kalsidiol median kasus 35,94 ng/ml dan kontrol 20,89 ng/ml berbeda bermakna (p=0,0001). Variasi gen CYP27B1 pada kedua kelompok berbeda bermakna (p=0,0001), dengan polimorfisme TT kasus 28% dan kontrol 19%. Hubungan konsentrasi kalsidiol dengan polimorfisme gen CYP27B1 berbeda bermakna (p=0,0001), tidak terdapat hubungan konsentrasi kalsidiol dengan aliran TIMI dan polimorfisme gen CYP27B1 dengan p=0,232. Konsentrasi kalsidiol tinggi pada kasus dimungkinkan sebagai respon tubuh terhadap inflamasi yang mengalami serangan jantung. Polimorfisme TT kasus 28% tidak memiliki hubungan terhadap patofisiologi aliran TIMI akhir.

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STEMI is an AMI with a high risk of mortality. The risk is reduced by revascularization called by IKPP Cardiovascular disorders are associated with decreased vitamin D concentrations. The decrease could be due to the SNP gene CYP27B1 which encodes the enzyme 1α hydroxylase and no studies have linked vitamin D concentrations in STEMI patients undergoing IKPP. IKPP results in the form of block area and the ability of blood to flow to the coronary blood vessels, known as TIMI grade 0-3. The aim of this study was to analyze the relationship between calcidiol concentrations and the CYP27B1 gene (-rs10877012) G to T changes in STEMI undergoing IKPP with TIMI flow. One hundred STEMI and control subjects collected 3 mL of blood. Plasma concentration of calcidiol was measured using the ELISA technique. PBMCs were analyzed CYP27B1 gene (- rs10877012) by taqman probe qRT PCR. Data were analyzed by statistical significance of 0.05. Median calcidiol concentration of 35.94 ng / ml cases and 20.89 ng / ml controls was significantly different (p = 0.0001). CYP27B1 gene variation in the two groups was significantly different (p = 0.0001), with TT polymorphism of 28% and 19% of controls. The correlation between calcidiol concentration and CYP27B1 gene polymorphism was significantly different (p = 0.0001), there was no correlation between calcidiol concentration and TIMI flow and CYP27B1 gene polymorphism with p = 0.232. The high calcidiol concentration in this case may be the body's response to inflammation following a heart attack. The TT polymorphism of 28% cases had no relationship to the pathophysiology of late TIMI flow."

"Studi mengenai pemberian klopidogrel sebelum angiografi koroner (pretreatment) pada pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) yang akan menjalani intervensi koroner perkutan primer (IKPP) terbatas, namun dapat disimpulkan bahwa aman dan dapat penurunan angka major adverse cardiovascular events (MACE). Pada studi yang dilakukan beberapa tahun terakhir, manfaat pemberian klopidogrel pretreatment dipertanyakan. Studi yang telah ada dilakukan di negara lain berbeda dengan kondisi di Indonesia; terdapat perbedaan karakteristik seperti waktu onset nyeri dada hingga pasien sampai ke fasilitas kesehatan primer, loading antiplatelet, serta dilakukan tindakan IKPP yang lebih panjang. Penelitian ini bertujuan untuk mengetahui hubungan pemberian klopidogrel pretreatment  dengan TIMI-flow pasien IMA EST yang menjalani IKPP. Studi potong lintang retrospektif terhadap 220 pasien IMA EST dilakukan di rumah sakit Jantung dan Pembuluh Darah Harapan Kita sejak tanggal 1 Januari - 30 Oktober 2018 dengan membagi subjek dalam kelompok klopidogrel pretreatment (600 mg klopidogrel diberikan > 120 menit sebelum angiografi koroner) dan kelompok yang diberikan < 120 menit. Analisis multivariat menunjukkan bahwa klopidogrel pretreatment merupakan prediktor utama yang mempengaruhi TIMI flow sebelum tindakan IKPP (OR 0.273, 95% CI 0.104-0.716; p=0.008). Pemberian klopidogrel pretreatment berhubungan dengan TIMI flow sebelum tindakan IKPP, namun tidak berpengaruh terhadap TIMI setelah dilakukan tindakan IKPP. 

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Immediate antiplatelet administration is the standard therapy used in acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Studi on clopidogrel pretreatment are limited, but it can be concluded that was safe, also reduced the number of major adverse cardiovascular events (MACE). Recently, pretreatment with P2Y12 are questioned. There are differences in the background and the conditions between the studies that have been conducted and the condition in Indonesia; such as duration of angina onset until arrive at primary health care, time of loading antiplatelet and longer ischemic time.

This study sought to evaluate the association between clopidogrel pretreatment and TIMI flow of patients with acute STEMI undergoing primary PCI. Single-center retrospective cross sectional study of 220 patients with acute STEMI were conducted in National Centre of Cardiovascular Harapan Kita, Indonesia from 1 January-30 October 2018. Subjects are devided into two groups: clopidogrel pretreatment (≥ 120 minute from coronary angiography conducted) and non pretreatment group (<120 minute). Multivariate analysis revealed that clopidogrel pretreatment is the main predictor of preprocedural TIMI grade flow (OR 0.273, 95% CI 0.104-0.716; p=0.008). Clopidogrel pretreatement was associated with TIMI flow grade pre intervention, but not with TIMI flow grade post intervention."