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Abstrak :
Preeklampsia merupakan penyulit kehamilan yang ditandai dengan hipertensi, edema dan proteinuria. Berdasarkan tanda-tanda tersebut, diduga disfungsi endotel memegang peranan dalam patogenesis kedua penyakit tersebut. Penelitian ini bertujuan untuk mengetahui apakah pada preeklampsia terjadi disfungsi endotel dengan memeriksa kadar sVCAM-1, vWF dan fibrin monomer sebagai petanda aktivasi koagulasi. Juga ingin diketahui apakah terdapat hubungan antara disfungsi endotel dengan beratnya penyakit. Desain penelitian potong lintang. Subyek penelitian adalah 30 orang wanita hamil 24 - 42 minggu dengan diagnosis preeklampsia yang bersedia ikut dalam penelitian dan kelompok kontrol terdiri atas wanita hamil aterm. Pemeriksaan kadar sVCAM-1 dikerjakan dengan cara ELISA dengan reagen dari R&D system. Kadar vWF ditentukan dengan cara enzyme linked fluorescent assay (ELFA) dengan reagen dari VIDAS bioMerieux. Fibrin monomer diperiksa dengan cara ethanol gelation test. Rerata dan simpang baku kadar sVCAM-1 pada preeklampsia dan kontrol berturut-turut adalah 576,4 ng/mL dan 58,3 ng/mL serta 375,7 ng/mL dan 43 ng/mL (p<0,05). Sedang rerata dan simpang baku kadar vWF pada preeklampsia dan kontrol berturut turut 305,3% dan 107,4% serta 162,4% dan 33% (p,0,05). Didapatkan korelasi sedang antara kadar sVCAM-1 dengan tekanan sistolik maupun diastolik (r=0,71) dan (r=0,65). Demikian pula antara kadar vWF dengan tekanan sistolik dan diastolik didapatkan korelasi sedang (r=0,67) dan (r=0,77). Fibrin monomer positif didapatkan pada 28 dari 30 penderita preeklampsia sedang pada kelompok kontrol hanya 1 orang yang positif. Hasil penelitian ini menunjukkan bahwa pada preeklampsia terjadi disfungsi endotel. Pada preeklampsia terdapat korelasi antara petanda disfungsi endotel dengan tingginya tekanan darah.

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Endothelial Dysfunction In Preeclampsia. Preeclampsia is a complication of pregnancy characterized by hypertension, edema, and proteinuria. Based on these signs, it is suggested that endothelial dysfunction plays a role in the pathogenesis of preeclampsia. The aims of this study were to know whether endothelial dysfunction occur in preeclampsia by measuring the level of sVCAM-1, von Willebrand factor, and fibrin monomer. The relationship between markers of endothelial dysfunction and blood pressure would also be sought. In this cross-sectional study, 30 women at the 24-42 weeks of pregnancy with preeklampsia, were enrolled and control group comprised of fullterm pregnant women. The level of sVCAM-1 was determined by ELISA method using reagents from R&D system, while vWF level was measured by enzyme linked fluorescent assay (ELFA) using reagent from VIDAS bioMerieux, and fibrin monomer was detected by ethanol gelation test. The mean of sVCAM-1 level in the preeklampsia group and in the control group were 576.4 ng/mL, and 375.7 ng/mL, respectively while the standard deviation were 58.3 ng/mL, and 43 ng/mL, respectively. The mean of vWF level in the preeklampsia group and in the control group were 305.3% and 162.4%, respectively while the standard deviation were 107.4% and 33%, respectively. Moderate correlation were found between sVCAM-1 as well as vWF level with both systolic and diastolic pressure. Fibrin monomer was found in 28 out of 30 subjects of preeclampsia group, but only 1 out of 31 subjects in the control group. The results of this study indicated that endothelial dysfunction occurred in preeclampsia.

Abstrak :
LATAR BELAKANG: Hipertensi merupakan salah satu masalah kesehatan yang turut berperan dalam peningkatan angka morbiditas dan mortalitas stroke, gagal jantung dan gagal ginjal. Morbiditas dan mortalitas hipertensi meningkat dengan makin banyaknya faktor risiko yang dimiliki, makin tinggi tekanan darah dan makin lama seseorang menderita hipertensi. Sampai saat ini mekanisme pasti terjadinya hipertensi belum jelas. Belakangan ini disfungsi endotel juga dikaitkan dengan hipertensi. Tujuan penelitian ini untuk mendapatkan gambaran kadar sVCAM-1 dan MAU, membuktikan adanya hubungan antara kadar sVCAM-1 dan MAU, menganalisis pengaruh usia, gender, obesitas, terkendali tidaknya hipertensi, lama sakit dan kadar kolesterol terhadap kadar sVCAM-1 dan MAU pada penderita hipertensi primer. BAHAN DAN METOPE: Penelitian ini menggunakan 65 subyek non diabetik dengan kadar hs-CRP < 5 mgIL dan protein win < 3+. Dilakukan pemeriksaan kadar sVCAM-1, K-LDL, albumin dan kreatinin urin terhadap subyek dengan protein win negatif atau trace, sedangkan subyek dengan protein urin 1+ atau 2+ hanya dilakukan pemeriksaan kadar sVCAM-1 dan K LDL. Penetapan kadar sVCAM-1 berdasarkan prinsip quantitative sandwich enzyme immunoassay, penetapan kadar K-LDL berdasarkan prinsip enzimatik homogen, penetapan kadar albumin urin berdasarkan prinsip imunoturbidimetri, penetapan kreatinin urin berdasarkan metode kinetik Jaffe dan MAU dinyatakan dengan rasio albumin 1 kreatinin urin. HASIL: Hasil penelitian menunjukkan proporsi kadar sVCAM-1 tinggi sebesar 81,5 % dan MAU 27,7 %. Kadar sVCAM-1 tinggi dan MAU lebih banyak dijumpai pada subyek tua, lelaki, hipertensi tak terkendali, lama sakit > 10 tahun dan obese. Dari hasil analisis multivariat derigail regresi rr ultipel, Adak didapatkan korelasi -yang bermakna antara kadar sVCAM-1 dengangender dan lama sakit namun didapatkan korelasi yang bermakna antara kadar sVCAM-1 dengan usia, MAP dan K-LDL. Hubungan tersebut dapat digambarkan melalui suatu persamaan yaitu kadar sVCAM-1 = 175 + 9,7 x usia (tahun) + 5,9 x MAP (mmHg) -- 2,9 x kadar K-LDL (rngldL) dengan nilai R2 adjusted sebesar 23,1 %. Tidak didapatkan korelasi yang bermakna antara MAU dengan usia, gender, MAP. 1MT, lama sakit dan K-LDL.Tidak didapatkan korelasi yang bermakna antara kadar sVCAM-1 dan rasio A 1 K. KESIMPULAN: Berdasarkan hasil penelitian ini didapatkan proporsi kadar sVCAM-1 tinggi 81,5 % dan MAU 27,7 %. Hal ini menunjukkan bahwa pada penderita hipertensi primer telah terjadi disfungsi endotel. Dari analisis multivariat menunjukkan kadar sVCAM-1 berkorelasi dengan usia, MAP dan K-LDL, sedangkan MAU tidak berkorelasi dengan variabel tersebut. Kadar sVCAM-1 tidak berkorelasi dengan MAU.

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Hypertension is a health problem which contributes in the increase morbidity and mortality of stroke, heart failure, and renal failure. The morbidity and mortality of hypertension were influenced by various risk factors, the height of blood pressure and the lenght of illness. The mechanism of hypertension up to now remains unclear. Recently, endothelial dysfunction has been associated with hypertension. The aims of this study were to obtain the level of sVCAM-1 and microalbuminuria (MAU) in primary hypertension, to analyse the relationship between sVCAM-1 level and MAU, to analyse the influences of age, gender, obesity, control of hypertension, length of illness, and the level of LDL cholesterol on sVCAM-1 level and MAU. Sixty five non diabetic subjects with hs-CRP level < 5 mg/L and protein urine < 3 + were enrolled in this cross sectional study. The level of sVCAM-1 were performed on all subjects by ELISA using reagents from R&D system, while MAU was determined by calculated the albumin : creatinine ratio in the urine. The level of LDL cholesterol was performed by homogenous enzymatic assay. The results indicated that the proportion of increase of sVCAM-1 level was 81.5% and MAU was 27.7% in primary hypertension. Increase of sVCAM-1 level and MAU were found more frequently in older subjects, male, uncontrolled hypertension, length of illness more than 10 years, and obese subject. The results of multivariate analysis with multiple regression showed that sVCAM-1 level significantly correlated with age, mean arterial pressure (MAP), and LDL cholesterol level, but did not correlate with gender, and length of illness. The relationship could be formulated as: sVCAM-1 level = 175 + 9.7 x age (years) + 5.9 x MAP ( mm Hg) -- 2.9 x LDL cholesterol level (mgldL) with R2 adjusted 23.1%. There were no correlation between MAU with age, gender, MAP, obesity, ienght of illness, and LDL cholesterol level. The level of sVCAM-1 did not correlate with albumin:creatinine urine ratio (MAU). Based on high proportion of increased sVCAM-1 and MAU, it is concluded that endothelial dysfunction occur in primary hypertension. The level of sVCAM-1 significantly correlates with age, MAP, and LDL cholesterol level, while MAU does not correlate with these variables. There is no correlation between sVCAM-1 level and MAU.

Abstrak :
ABSTRAK
Penelitian ini bertujuan untuk mengetahui efek pemberian hidroksiklorokuin 400 mg selama 12 minggu terhadap kadar sVCAM-1 dan sE-Selectin sebagai petanda disfungsi endotel pada pasien artritis reumatoid. Penelitian ini juga melihat peran HOMA-IR, FFA dan ox-LDL terhadap perbaikan disfungsi endotel.Penelitian ini menggunakan dua disain yaitu uji klinis acak tersamar ganda dan kohort prospektif dilakukan pada pasien artritis reumatoid dengan terapi metotreksat di poliklinik Reumatologi RS Cipto Mangunkusumo, Jakarta, pada periode Februari 2016-Mei 2017. Pasien dengan terapi insulin, anti-hipertensi dan terapi lain yang mempengaruhi kadar sVCAM-1 dan sE-Selectin dieksklusi dari penelitian. Subjek yang eligibel dirandomisasi menjadi dua kelompok, kelompok yang mendapat hidroksiklorokuin HCQ 400 mg dan kelompok placebo, dan diikuti selama 12 minggu. Pemeriksaan sVCAM-1, sE-Selectin, HOMA-IR, FFA dan ox-LDL dilakukan pada awal penelitian dan pada minggu ke-12. Perbedaan persentase perubahan kadar sVCAM-1 dan sE-Selectin sebelum dan setelah perlakuan antara kedua kelompok dianalisis dengan uji-t dan uji Mann-Whitney. Persentase perubahan kadar sVCAM-1 dan sE-Selectin dikorelasikan dengan persentase perubahan HOMA-IR, FFA dan ox-LDL, dengan uji Spearman.Sebanyak 37 subjek diikutkan dalam penelitian, dan terdapat 3 subjek yang drop-out pada masing-masing kelompok, sehingga didapatkan 15 subjek pada kelompok HCQ dan 16 subjek pada kelompok placebo. Kadar sVCAM-1 serum minggu ke-12 pada kelompok HCQ menurun sebesar 17,1 median , sementara pada kelompok plasebo meningkat sebesar 9,7 , dan perbedaan tersebut bermakna secara statistik. Kadar E-Selectin pada kelompok terapi HCQ mengalami penurunan dalam persen yang lebih besar dibandingkan pada kelompok plasebo, tapi perbedaan tersebut tidak bermakna. Perubahan kadar sVCAM-1 dan sE-Selectin, juga dibuktikan tidak berkorelasi dengan perubahan HOMA-IR, FFA dan ox-LDL.Terapi hidroksiklorokuin pada pasien artritis reumatoid terbukti memperbaiki disfungsi endotel dengan menurunkan kadar sVCAM-1, namun tidak terbukti menurunkan sE-Selectin. Variable sVCAM-1 dan sE-Selectin tidak berkorelasi dengan HOMA-IR, FFA dan ox-LDL Kata kunci: artritis reumatoid, disfungsi endotel, hidroksiklorokuin, sE-Selectin, sVCAM-1.

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ABSTRACT
This study aims to evaluate the effect of hydroxychloroquine on sVCAM 1 and sE Selectin levels decreasing as endothelial dysfunction marker in rheumatoid arthritis patients. This study also assessed the correlation between changes in sVCAM 1 and sE Selectin levels with other variables of changes in HOMA IR, FFA and ox LDL.Two kinds of methods i.e. double blind randomized controlled trial and prospective cohort, were conducted, on patients with rheumatoid arthritis with methotrexate treatment at Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital Faculty of Medicine Universitas Indonesia, Jakarta, during February 2016 July 2017. Patients with insulin, anti hypertension and other treatment which could affect sVCAM 1 and sE Selectin level, were excluded. Eligible subjects were randomly assigned into two groups. Eighteen subjects were administered hydroxychloroquine 400 mg daily and 19 patients were given placebo for 12 weeks. sVCAM 1, sE Selectin, HOMA IR, FFA dan ox LDL were examined in the beginning and in the end week 12. Differences of serum sVCAM 1 and sE Selectin level in percentage, before and after experiment, were evaluated, by T test or alternatively by Mann Whitney test. Differences of serum sVCAM 1 and sE Selectin level in percentage, were correlated with difference of serum HOMA IR, FFA and ox LDL level, by Spearman test.There were 37 subjects enrolled in the study, and there were 3 drop out subjects in each group, finally there were 15 subjects in the HCQ group and 16 in the placebo group. Serum sVCAM 1 level decreased 17.1 median in HCQ treatment group, while in placebo group, it increased 9,7 median compared with pre treatment value. The difference in percentage rate change of sVCAM between two group was significant. On the other hand, the change of E Selectin serum level in HCQ group was found a higher percentage of decrease compared with placebo group, but the difference was not significant. Changes in sVCAM 1 and sE Selectin levels were also proven no correlation with HOMA IR, FFA and ox LDL changes.Treatment of HCQ in patients with rheumatoid arthritis appears beneficial to improve endothelial dysfunction by lowering serum sVCAM 1, but not proven to decrease sE Selectin. The sVCAM 1 and sE Selectin variables were not correlated with HOMA IR, FFA and ox LDL Keywords endothelial dysfunction, hydroxychloroquine, rheumatoid arthritis, sE Selectin, sVCAM 1.