Haryati, Lina (2017) Perbedaan Respon Terapi Berbasis Angiotensin Ii Receptor Blocker (Arb) Terhadap Regresi Massa Ventrikel Kiri Pada Pasien Hipertensi Dengan Polimorfisme Reseptor ß1- Adrenergik Arg389gly Di Rumah Sakit Saiful Anwar Malang. Magister thesis, Universitas Brawijaya.
Abstract
Latar belakang: Hipertrofi Ventrikel Kiri (HVK) adalah salah satu komplikasi hipertensi yang akan meningkatkan morbiditas dan mortalitas. Angiotensin II dan stimulasi kronik pada reseptor β1-adrenergik (β1-AR) berkontribusi terhadap progresifitas HVK pada pasien hipertensi. Angiotensin II Receptor Blocker (ARB) merupakan golongan obat antihipertensi yang terbukti efektif menurunkan indeks massa ventrikel kiri. Penelitian sebelumnya menunjukkan bahwa polimorfisme Arg389Gly gen reseptor β1-adrenergik mempunyai risiko yang lebih tinggi terhadap terjadinya HVK pada pasien hipertensi essensial. Belum ada data tentang perbedaan respon terapi berbasis ARB terhadap regresi massa ventrikel kiri pada pasien hipertensi dengan polimorfisme reseptor β1-adrenergik Arg389Gly di Indonesia. Tujuan: Mengidentifikasi perbedaan respon terapi berbasis ARB terhadap regresi massa ventrikel kiri pada pasien hipertensi dengan polimorfisme reseptor β1-adrenergik Arg389Gly di Rumah Sakit Saiful Anwar Malang. Desain dan metode: Penelitian observasional kohort prospektif pre dan post test ini melibatkan 39 pasien dengan kriteria inklusi: laki-laki; usia 40-75 tahun; hipertensi (Tekanan Darah ≥140/90 mmHg) yang belum/ tidak dalam terapi antihipertensi atau drop out dari terapi antihipertensi selama minimal 2 minggu atau untolerable terhadap Angiotensin Converting Enzim (ACE) Inhibitor; memiliki asuransi kesehatan, memiliki kepatuhan tingkat tinggi (skore 8 dalam menjawab kuesioner Morisky Medication Adherence Scale (MMAS)) dalam menjalani terapi; dan bersedia menandatangani informed consent penelitian. Kriteria ekslusi dalam penelitian ini yaitu: terdapat penyakit berat yang dapat membatasi longterm survival, diabetes mellitus, stroke, hypertrophic cardiomyopathy, valvular heart disease, hipertensi pulmonal, penyakit jantung koroner, gagal jantung kiri stage C atau D, gangguan fungsi ginjal, gangguan fungsi hati, perdarahan aktif, atau pasien yang sedang dalam terapi kortikosteroid. Pasien menjalani prosedur Ambulatory Blood Pressure Monitoring (ABPM) 24 jam, pemeriksaan ekokardiografi untuk menilai HVK sebelum dan setelah 6 bulan pemberian terapi antihipertensi berbasis ARB dan regimen selama follow-up dioptimalisasi berdasarkan tekanan darah office. Polimorfisme reseptor β1-adrenergik Arg389Gly diperiksa dengan menggunakan metode Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) dan dikonfirmasi dengan metode sequenzing. Hasil: Pada populasi hipertensi penelitian ini didapatkan frekuensi genotype Arg389Arg sebanyak 46,15% dan Arg389Gly/ Gly389Gly 53,85%, sedangkan pada kelompok HVK didapatkan frekuensi genotype Arg389Arg sebanyak 23,08% dan Arg389Gly/ Gly389Gly 17,95%. Pemberian terapi ARB setelah 6 bulan baik menggunakan Valsartan maupun Telmisartan pada pasien hipertensi dengan genotipe Arg389Arg dan Arg389Gly/ Gly389Gly, menunjukkan tidak ada perbedaan respon terapi yang signifikan baik tekanan darah sistolik dan diastolik 24 jam, LVMi, LV mass, maupun RWT (Relative Wall Thickness). Penambahan beta-blocker (Bisoprolol) pada terapi berbasis ARB dalam kelompok pasien dengan genotype Arg389Arg menunjukkan regresi LVMI dari 137,50 ± 22,62 menjadi 63,67 ± 28,08 (p=0.028), regresi LV mass dari 240,17 ± 40,14 menjadi 130,67 ± 22,39 (p=0.028), dan regresi RWT dari 0,49 ± 0,08 menjadi 0,36 ± 0,11 setelah 6 bulan, sedangkan pada kelompok genotype Arg389Gly/ Gly389Gly menunjukkan respon regresi LVMI, LV mass, dan RWT yang tidak signifikan. Kesimpulan: Pengobatan dengan antihipertensi berbasis ARB selama 6 bulan menunjukkan tidak ada perbedaan respon terapi regresi tekanan darah sistolik dan diastolik 24 jam, LVMI, LV mass, dan RWT yang signifikan baik pada kelompok pasien hipertensi dengan genotype Arg389Arg maupun kelompok genotype Arg389Gly/Gly389Gly. Penambahan beta-blocker (Bisoprolol) pada terapi berbasis ARB menghasilkan regresi HVK yang signifikan pada pasien hipertensi kelompok genotype Arg389Arg dibandingkan pemberian tunggal ARB, sedangkan pada kelompok genotype Arg389Gly/Gly389Gly pemberian ARB baik tunggal atau dengan penambahan beta-blocker tidak memberikan respon terapi regresi HVK yang signifikan.
English Abstract
Background: Left Ventricular Hypertrophy (LVH) is once of hypertensive complications that will increase morbidity and mortality rate. Angiotensin II and chronic stimulation of β1-adrenergic receptors (β1-AR) contribute to the progression of LVH in hypertensive patients. Angiotensin II Receptor Blocker (ARB) is a class of antihypertensive drugs that has been shown to effectively lower left ventricular mass index. The previous research showed that the Arg389Gly polymorphism of the β1-AR gene confered higher risk of LVH in human essential hypertension. The absence of data of the left ventricular mass regression in hypertensive patients with Arg389Gly polymorphism of the β1-AR gene in Indonesia. Objective:This study aims to Identified differences in ARB-based therapy response to left ventricular mass regression in hypertensive patients with Arg389Gly β1-adrenergic receptor polymorphism at Saiful Anwar Hospital Malang. Desain and methods: This prospective pre and post test cohort study included 39 patients with inclusion criterias: men; 40-75 years old; hypertension (blood pressure ≥140 / 90 mmHg) that has not / not been in antihypertensive therapy or dropped out of antihypertensive therapy for at least 2 weeks or untolerable to Angiotensin Converting Enzyme (ACE) Inhibitor; have health insurance, have high adherence (score 8 in answering the Morisky Medication Adherence Scale (MMAS) questionnaire in therapy; and willing to sign research informed consent. The exclusion criterias in this study are: severe disease that can limit longterm survival, diabetes mellitus, stroke, hypertrophic cardiomyopathy, valvular heart disease, pulmonary hypertension, coronary heart disease, left heart failure st C or D, impaired renal function, impaired liver function, active bleeding, or patients who are on corticosteroid therapy. Patients underwent 24-hour Ambulatory Blood Pressure Monitoring (ABPM) procedures, echocardiographic examination to assess HVK before and after 6 months of ARB-based antihypertensive therapy and the regimen during follow-up was optimized based on office blood pressure. Arg389Gly β1-adrenergic receptor polymorphism was examined using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method and confirmed by sequenzing method. Results: In hypertension population this research obtained frequency genotype Arg389Arg as much 46.15% and Arg389Gly / Gly389Gly 53.85%, whereas in the LVH group obtained the genome frequency Arg389Arg as much as 23.08% and Arg389Gly / Gly389Gly 17.95%. The ARB-based therapy after 6 months using either Valsartan or Telmisartan in hypertensive patients with Arg389Arg and Arg389Gly / Gly389Gly genotypes showed no significant difference in response of either 24-hour systolic and diastolic blood pressure, LVMi, LV mass, or RWT (Relative Wall Thickness ). The addition of beta-blockers (Bisoprolol) to ARB-based therapy in the group of patients with the Arg389Arg genotype showed LVMI regression from 137.50 ± 22.62 to 63.67 ± 28.08 (p = 0.028), LV mass regression of 240.17 ± 40.14 to 130.67 ± 22.39 (p = 0.028), and RWT regression from 0.49 ± 0.08 to 0.36 ± 0.11 after 6 months, whereas in the genotype group Arg389Gly / Gly389Gly showed regression response LVMI, LV mass, and RWT are not significant. Conclusions: Our study show that ARB-based antihypertensive treatment for 6 months showed no significant difference in regression response of 24-hour systolic and diastolic blood pressure, LVMI, LV mass, and RWT in both the hypertension group and the Arg389Arg genotype and the Arg389Gly / Gly389Gly genotype group. The addition of beta-blockers (Bisoprolol) to ARB-based therapy resulted in significant LVH regression in patients with Arg389Arg genotype hypertension group compared to single ARB, whereas in the genotype group Arg389Gly / Gly389Gly either single ARB or with the addition of beta-blockers did not response to LVH regression significantly.
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/616.132/HAR/p/2017/041705269 |
| Uncontrolled Keywords: | ANGIOTENSIN II, HYPERTENSION, GENETIC POLYMORPHISMS |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.1 Diseases of cardiovascular system > 616.13 Diseases of blood vessels > 616.132 Hypertension |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | Nur Cholis |
| Date Deposited: | 20 Jul 2017 03:01 |
| Last Modified: | 01 Nov 2020 07:09 |
| URI: | http://repository.ub.ac.id/id/eprint/400 |
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