The effect of losartan on the intima-media thickness of carotid artery/Losartanin karotid arter intima-media kalinligina etkisi.OZET Amac: Ateroskleroz olusumunun her evresinde, angiotensin angiotensin /an·gio·ten·sin/ (-ten´sin) a decapeptide hormone (a. I) formed from the plasma glycoprotein angiotensinogen by renin secreted by the juxtaglomerular apparatus. 1 (AT1) reseptor etkinliginin olumsuz islevleri olduguna dair bulgular vardir. Gunumuzde AT1 reseptor uzerinde yogun arastirmalar yapilmakta ve aterosklerozun geriletilmesinde AT1 reseptor antagonistlerinin etkisi arastirilmaktadir. Karotis arter duvar kalinligi olcumu ise aterosklerozun bir belirteci olarak kabul edilmistir. Bu calismamizda, hipertansif hastalarda kullanilan AT1 reseptor blokeri losartanin karotis arter intima-media kalinligina (IMK IMK Institut für Marketing und Kommunikation (German) IMK Instituti I Monumenteve Të Kulturës (Albanian: Institute of Cultural Monuments) IMK Indeo Media Kit ) etkisini arastirdik. Yontemler: Tabakali rasgele ornekleme yontemiyle ulasilan 450 kisiden tani konulmamis hipertansiyon hastasi oldugu saptananlardan calismamiza katilmayi kabul eden 51 olgu calisilmaya alindi. Yas ortalamasi 54[+ or -]9 yil olan 33 bayan, 16 bay olgu ile calisma tamamlandi. Biyokimyasal degerleri yani sira usulune uygun olarak kan basinclari olculdu. Karotis arter ve dallarinda B-Mod Doppler ile duvar kalinliklari olculup antihipertansif olarak Losartan sagaltimina baslandi. Sekizinci ayda duvar kalinlik olcumleri yinelendi. Bulgular: Olgularin baslangicta sistolik (SKB SKB Smithkline Beecham SKB Steve Kimock Band SKB St Kitts, Saint Kitts And Nevis - Golden Rock (Airport Code) SKB Sportsklubben Brann (football club, Norway) SKB Smart Knee Board ) ve diyastolik (DKB DKB Dürener Kreisbahn (German) DKB Dresdner Kleinwort Benson DKB Dancers Kick Butt DKB Daichi Kaigin Bank DKB Device Key Block ) kan basinci ortalamalari sirasiyla 167[+ or -]14 mmHg ve 102[+ or -]8 mmHg idi. Sekizinci ay sonunda bu degerler sirasiyla 139[+ or -]11 mmHg ve 84[+ or -]8 mmHg'ya gerilemisti (p<0.05). Karotis arter intima intima /in·ti·ma/ (in´ti-mah) 1. innermost. 2. tunica intima vasorum.in´timal in·ti·ma n. pl. media kalinliklarinda, ortalama olarak, bayanlarda 0.10[+ or -]0.19 mm (p=0.004), baylarda 0.18[+ or -]0.29 mm (p= 0.007) ve tum olgularda 0.13[+ or -]0.23 mm (p<0.001) olarak anlamli gerileme olustugu saptandi. Olgularin sagaltim oncesi SKB veya DKB ile ortalama karotis arter duvar kalinligi arasinda bir baginti gorulmedi (sirasiyla r=0.122, p=0.403 ve r=0.032, p=0.828). Sonuc: Losartanin, hipertansiyondan baska, fazla sayida ateroskleroz tehlike etkeni tasiyan bireylerde, erken yaslarda aterosklerozdan korunma amaci ile de kullanilmasinin onerilmesi ve bunun tartisilmasi gerektigi kanisindayiz. (Anadolu Kardiyol Derg 2008; 8: 197-205) Anahtar kelimeler: Losartan, ateroskleroz, karotis arteri, intima-media kalinligi, hipertansiyon ABSTRACT Objective: There are findings about negative effects of angiotensin 1 (AT1) receptor stimulation at every stage of atherosclerosis atherosclerosis (ăth'ərōsklərō`sĭs): see arteriosclerosis. atherosclerosis or hardening of the arteries formation. Recently, AT1 receptors, especially the effects of AT1 receptor antagonists A receptor antagonist is a drug that does not provoke a biological response itself upon binding to a receptor, but blocks or attenuates agonist-mediated responses. It may be competitive (or surmountable), i.e. on the regression of atherosclerosis, are being researched intensively. Measurement of carotid artery carotid artery n. 1. An artery that originates on the right from the brachiocephalic artery and on the left from the aortic arch, runs upward into the neck and divides opposite the upper border of the thyroid cartilage, with the external and thickness has been accepted as a marker of atherosclerosis. In our study, we investigated the effect of AT1 receptor antagonist, losartan, on the carotid artery intima-media thickness Intima-media thickness (IMT), also called intimal medial thickness, is a measurement of the thickness of artery walls, usually by external ultrasound, occasionally by internal, invasive ultrasound catheters, see IVUS, to both detect the presence and to track the progression of of newly diagnosed hypertensive hypertensive /hy·per·ten·sive/ (-ten´siv) 1. characterized by increased tension or pressure. 2. an agent that causes hypertension. 3. a person with hypertension. patients. Methods: We reached to 450 individuals by the stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers. strat·i·fied adj. Arranged in the form of layers or strata. and random sampling method and measured their blood pressure to find out undiagnosed hypertensive patients. Fifty-one patients (mean age 54[+ or -]9 years) were accepted to participate in our study. Forty-nine of them (33 women and 16 men) completed the study. After the measurements of the carotid artery intima-media thicknesses by B-mode Doppler ultrasonography Doppler Ultrasonography Definition Doppler ultrasonography is a non-invasive diagnostic procedure that changes sound waves into an image that can be viewed on a monitor. , their blood tests were performed and arterial blood arterial blood n. Blood that is oxygenated in the lungs, is found in the left chambers of the heart and in the arteries, and is relatively bright red. pressures were measured. Soon after, treatment with losartan as an antihypertensive antihypertensive /an·ti·hy·per·ten·sive/ (-ten´siv) counteracting high blood pressure, or an agent that does this. an·ti·hy·per·ten·sive adj. Reducing high blood pressure. n. agent was begun. All measurements were repeated on the eighth month of this therapy. Results: The mean systolic Systolic The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest. and diastolic blood pressure Diastolic blood pressure Blood pressure when the heart is resting between beats. Mentioned in: Hypertension of the cases were 167[+ or -]14 mmHg and 102[+ or -]8 mmHg, respectively. At the end of the eighth month these measurements regressed to 139[+ or -]11 mmHg and 84[+ or -]8 mmHg, respectively (p<0.05). Meaningful regression of carotid artery intima-media thickness was established. The mean regression was 0.10[+ or -]0.19 mm (p=0.004) for women, 0.18[+ or -]0.29 mm (p=0.007) for men and 0.13[+ or -]0.23 mm (p<0.001) for the study population. No relation was seen between the carotid artery intima-media thickness and first systolic and diastolic blood pressure measurements of the patients (r=0.122, p=0.403 and r=0.032, p=0.828, respectively). Conclusion: We think that losartan should be recommended to use for protection against atherosclerosis at the young aged individuals that have multiple risks for atherosclerosis, other than hypertension hypertension or high blood pressure, elevated blood pressure resulting from an increase in the amount of blood pumped by the heart or from increased resistance to the flow of blood through the small arterial blood vessels (arterioles). . (Anadolu Kardiyol Derg 2008; 8: 197-205) Key words: Losartan, atherosclerosis, carotid artery, intima-media thickness, hypertension Giris Ateroskleroz, tum dunyada en sik olum sebebidir. Dunya Saglik Orgutu; 2020 yilinda aterosklerozun, sadece mortalite degil yasami kisitlayan sebeplerin de basinda gelecegini ongormektedir (1). Ateroskleroza gidiste genetik yatkinlik onemli bir etken olmakla birlikte olusuma yardimci cesitli tehlike etkenleri de mevcuttur (2). Aterojenik uyarilar sonucu ortaya cikan endotel disfonksiyonunun aterosklerozun baslangic evresi oldugu kabul edilmektedir (1). Son on yildir endotel disfonksiyonu ile ilgili arastirmalar anjiyotensin II'nin (AT-II) ateroskleroz baslangici ve ilerlemesinde bircok katki larinin varligina isaret etmektedir (3). Bunun uzerine calismalar renin renin /re·nin/ (re´nin) a proteolytic enzyme synthesized, stored, and secreted by the juxtaglomerular cells of the kidney; it plays a role in regulation of blood pressure by catalyzing the conversion of angiotensinogen to angiotensin I. anjiyotensin aldosteron sistemi (RAAS) uzerinde yogunlasmistir. Kan basincinin duzenlenmesi, noron islevleri, endotel islevleri, su ve tuz dengesinin saglanmasinda RAAS onemli bir duzenektir. Bu RAAS'nde etkin madde guclu bir vazokonstriktor olan AT-II'dir (4). Anjiyotensin II, etkilerini bircok reseptor araciligiyla; cogu etkilerini ise AT1 reseptoru uzerinden gostermektedir (5). Bu AT1 reseptorlerinin uyarilmasiyla, vazokonstruksiyon, damar Damar: see Dhamar, Yemen. duz kas hucre cogalmasi, damarsal dokuda bag doku ve dusuk yogunluklu lipoprotein lipoprotein (lĭp'əprō`tēn), any organic compound that is composed of both protein and the various fatty substances classed as lipids, including fatty acids and steroids such as cholesterol. kolesterol (DYL-K) birikimi olusur. Yani sira endotel islevlerinden ozellikle nitrik oksit salinimi baskilanir (6). Bu bulgular AT1 reseptorlerinin ateroskleroz icin olasi bir tehlike etkeni olabilecegini dusundurmustur. Aterosklerozun en erken evresi olan endotel disfonksiyonundan yagli cizgilenmeye, plak olusumundan yirtilmasi na dek her asamada, AT1 reseptor etkinliginin islevi olduguna dair bulgular vardir (7). Soz konusu AT1 ve AT2 reseptorleri birbirlerini dengeleyici sekilde calisirlar. Sonucta AT2 reseptorleri uyarildiginda nitrik oksit uretiminde artis, vazodilatasyon, antiproliferatif etki ve apoptozis ortaya cikar. Ayrica, hucre farklilasmasi, natriurez, doku hasarinin onarilmasi gibi etkileri de vardir (8). Gunumuzde AT1 reseptor aktivasyonu ve antagonistleri uzerinde yogun arastirmalar yapilmakta ve aterosklerozun geriletilmesinde AT1 reseptor antagonistlerinin etkisi arastirilmaktadir. Bu calismamizda Aydin ilinde yeni saptadigimiz hipertansif hastalarda kullanilan AT1 reseptor blokeri losartanin karotis arter intimamedia kalinligina (IMK) etkisini arastirdik. Bu sekilde losartanin aterosklerozu geriletici etkisinin olup olmadigini gostermeyi amacladik. Yontemler Arastirmamiz ileriye donuk tek kor bir calismadir. Losartanin IMK'na etkisini arastirmak icin, zaten antihipertansif ilac kullanmasi gereken yeni tani konulan hipertansif hastalar bulundu. Losartan baslanmasi oncesi ve sonrasinda B-mod karotis arter ultrasonografisi ile IMK olculdu. Olgu sayisinin cok fazla olamayisi disinda bir kisitliligimiz yoktu. Bunun da nedeni maliyetin yuksek olusu idi. Ayri ntilar asagida sunulmustur. Hasta secimi ve sorgulama Tani almamis hipertansif bireylerin saptanabilmesi amaciyla, Aydin Valiligi'nden gerekli izin belgesi alindiktan sonra, Aydin ili merkez, ilce ve koylerine gidildi. Tabakali rasgele ornekleme yontemi (9) ile karsilasilan 450 kisi ile ev ve isyerlerinde gorusuldu. Kendilerine arastirma hakkinda bilgi verilerek bu arastirmaya katilmak isteyip istemedikleri soruldu. Gorusulen 450 kisiden 300 kisi taramaya katilmayi kabul etti. Kabul eden kisilere daha onceden hazirlanmis bir belge ile sormaca (anket) uygulandi. Sormaca belgesinde ad, soyad, cinsiyet, yas, telefon numarasi gibi kimlik bilgileri alindi. Sigara kullanip kullanmadigi, boy ve kilosu, hipertansiyon tanisi olup olmadigi, antihipertansif ilac kullanip kullanmadigi soruldu. Ayri ca katilan kisiler ek hastaliklar ve kan basinclarini etkileyebilecek ilaclar yonunden de sorgulandi. Kan basinclari olculdu. Tum bilgiler ve kan basinci sonuclari sormaca belgesine kaydedildi. Kan basincinin olculmesi Katilimci 300 kisi, yaklasik 25[degrees]C oda sicakliginda, 10 dakika dinlendirildi. Kisilerin oturur durumda, her iki koldan olmak uzere ve 2 dakika arayla ikiser kez sfigmomanometre ile sistolik ve diyastolik kan basinclari usulune uygun olarak olculdu. Korotkoff seslerinin net olarak duyulmaya baslandigi (Korotkoff faz I) kan basinci duzeyi sistolik kan basinci, Korotkoff seslerinin kayboldugu kan basinci duzeyi (Korotkoff faz V) diyastolik kan basinci olarak degerlendirildi (10). Hastalar, 3 gun sonra kan basinclarinin tekrar olculmesi icin hastaneye cagirildi. Olcumden onceki 30 dk icinde sigara icilmemesi, alkol, kahve gibi icecekler alinmamasi belirtildi. Kan basinclari ayni sekilde olculerek kaydedildi. Kan basinci olcum tekrari, gozlemciler arasi farkliligi gidermek icin ayni kisi tarafi ndan yapildi. Fakat olcumu yapan gozlemci, katilimcinin 3 gun onceki kan basinci kaydina bakmadan olcum yapti. Kan basinclari her iki olcumde de sistolik 140 mmHg, diyastolik 90 mmHg'nin uzerinde olculenlere JNC JNC Joint National Committee JNC Japan Nuclear Cycle Development Institute JNC Judicial Nominating Commission JNC Jet Navigation Chart JNC Journal of Nuclear Cardiology JNC JNet Consultancy (Netherlands) VII uyarinca hipertansiyon tanisi konuldu (11). Hipertansif bulunan 60 olguya arastirma ile ilgili bilgi verilerek katilip katilmak istemedikleri soruldu. Olgulardan 54'u onay verdi ve calismaya alindi. Olgulara yaklasim Hastalarin oykuleri alindi. Ayrintili sistemik fizik bakilari yapildi. Sagaltima baslamadan once elektrokardiyogramlari cekildi. Vucut kitle indeksleri belirlendi. Dokuz-12 saatlik aclik sonrasinda aclik kan sekeri, serum potasyum, kreatinin, yuksek yogunluklu lipoprotein (YYL) ve dusuk yogunluklu lipoprotein (DYL DYL Doylestown, Pennsylvania (Airport Code) DYL Destroy Your Liver ) kolesterol, trigliserid (TG) degerleri ILab-900 cihazinda IL Test CK-NAC kitleri ile olculdu. Tiroid fonksiyon testleri (serbest T3, T4 ve TSH TSH thyroid-stimulating hormone; see thyrotropin. TSH abbr. thyroid-stimulating hormone Thyroid-stimulating hormone (TSH) ) Elecsys 2010 (Roche-Hitachi) cihazi ile Roche kitleri kullanilarak olculdu. Cushing, primer prim·er n. A segment of DNA or RNA that is complementary to a given DNA sequence and that is needed to initiate replication by DNA polymerase. aldosteronizm, uyku apne sendromu, tiroid ve paratiroid hastaliklari, kronik bobrek yetmezligi, renovaskuler hastalik, feokromositom, aort koarktasyonu gibi tanimlanabilir bir hipertansiyon nedeni dusundurmeyen ve kronik steroid sagaltimi ya da hipertansiyonu tetikleyebilen ilac kullanimi oykusu olmayan 51 olgu ile calismaya devam edildi. Diger uc hasta calisma disi birakildi. Bu 3 hastadan ikisinde hipertiroidi, birinde ise kronik bobrek yetmezligi saptanmisti. Calisma disi birakilan hastalar ileri inceleme ve sagalti m icin ilgili polikliniklere yonlendirildiler. Sagaltim baslangicindan sonraki ikinci ayda, kan basinci kontrollerinde, kan basinci regulasyonu icin ikinci bir antihipertansif ilaca gerek duyulan iki hasta daha calismadan cikarildi. Karotis arter ultrasonografi Arastirmaya katilan 51 hipertansif hastanin sagaltimina baslamadan once bilateral karotis arter IMK olculdu. Tum taramalar supin pozisyonda klinik bilgilerden habersiz uzman radyolog tarafindan yapildi. Ilac baslama tarihleri ve kontrol zamanlari konusunda radyologa bilgi verilmedi. B-mod ultrasonografi cihazi (EUB-420, HITACHI, Tokyo, Japonya) ve 7.5-MHz lineer transduser kullanildi. Sag ve sol ana karotis arter (AKA), internal karotis arter (IKA) ve eksternal karotis arter (EKA EKA Epoc Kernel Architecture (Symbian OS) EKA Ennis Knupp & Associates (Chicago, Illinois) EKA Extended Kirchhoff Approach ) belirli segmentleri lateral transduser acisi ile goruntulendi. Bulbus karotisten ya da bifurkasyondan 1 cm proksimalde AKA icin; IKA ve EKA icin ise bifurkasyondan 1 cm distalde sagittal sagittal /sag·it·tal/ (saj´i-t'l) 1. shaped like an arrow. 2. situated in the direction of the sagittal suture; said of an anteroposterior plane or section parallel to the median plane of the body. duzlemde goruntuler elde edilerek proba en uzak duvardan olcumler yapildi. Olcumlere plaklar dahil edilmedi. Plaklar ayrica belirlendi ve olculdu. Lumen lumen: see photometry. A unit of measurement of the amount of brightness that comes from a light source. Lumens define "luminous flux," which is energy within the range of frequencies we perceive as light. ile intima-media-adventisya arasindaki mesafeden IMK olculdu. Bir olguda olculen tum duvar kalinliklari, hem ait oldugu damar adiyla, hem de toplam ateroskleroz gostergesi icin tumunun ortalamasi seklinde de ele alindi. Ikinci IMK olcumu, sagaltimin sekizinci ayinda ayni sekilde yapildi. Losartan baslanmasi ve hasta gozlemi Iki tarasi karotis arter IMK olcumleri yapilan hastalara, 50 mg/gun Losartan potasyum baslandi (Cozaar 50 mg tablet, Merk Sharp Dohme, ABD ABD n. A candidate for a doctorate who has completed all the requirements for the degree, such as courses and examinations, with the exception of the dissertation. [a(ll) b(ut) d(issertation).] ). Ilaclar firma destegiyle degil; olagan receteleme islemiyle temin edildi. Hastalara ilaci her gun duzenli olarak almalari gerektigi ve iki ay arayla kan basinci olcumlerine gelecekleri anlatildi. Randevulari verildi. Ilk ilk 1 n. Type or kind: can't trust people of that ilk. pron. Scots The same. iki olcum on gun arayla yapilarak kan basinci yuksek seyreden hastalarda Losartan potasyum 100 mg/gun'e gecildi. Ayni sekilde ikiser ay arayla yapilan kan basinci olcumlerinde kan basinclari normale (sistolik kan basi nci<120 mmHg ve diyastolik kan basinci <80 mmHg) indirilemeyen hastalarda da (14 olgu) Losartan potasyum 100 mg/gun'e gecildi. Karotis arter ultrasonografi olcumleri sekizinci ayda tekrar yapildi. Istatistiksel yontemler Tum sonuclar SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. for Windows version 10 (Chicago, IL, USA) yaziliminda bilgisayara kaydedildi. Olgularimizdan toplanan verilerin irdelenmesinde tanimlayici istatistikler, Eslestirilmis-t testi, Mann-Whitney U In statistics, the Mann-Whitney U test (also called the Mann-Whitney-Wilcoxon (MWW), Wilcoxon rank-sum test, or Wilcoxon-Mann-Whitney test) is a non-parametric test for assessing whether two samples of observations come from the same , Wilcoxon T farklilik istatistikleri ile Pearson ve Spearman's baginti (korelasyon) istatistikleri yapildi. Once tum olgularda, baylarda, bayanlarda, plak saptananlarda, plak saptanmayanlarda ayri ayri tanimlayici istatistikler yapildi. Bay ve bayan olgularda yas, vucut kitle indeksi (VKI VKI Variable Keyframe Interval (DivX encoding algorithm) VKI Virtual Keyframe Interval ), aclik kan sekeri (AKS), TG, YYL, DYL ile sagaltim oncesi ve sonrasi sistolik kan basinci (SKB), diyastolik kan basinci (DKB), sag ve sol karotis arter duvar kalinliklari acisindan farklilik istatistigi yapmak uzere nonparametrik Mann Whitney U testi kullanildi. Kan basinci olcutu olarak SKB ve DKB sagaltim oncesi ve kontrol olcumlerini birbirleriyle karsilastirabilmek icin coklu tekrarli varyans analizi yapildi. Karotis arter duvar kalinliklarina losartanin etkisini degerlendirebilmek icin arastirma kitlesinde sagaltim oncesi ve sekizinci aydaki olcumler arasinda farklilik istatistigi yapildi. Yontem olarak eslestirilmis-t testi kullanildi. Bayanlarda ve baylarda karotis arter duvar kalinligi sagaltim oncesi ve sonrasi farklilik istatistigi icin olgu sayilarina uygun olarak baylar icin Wilcoxon T testi, bayanlar icin eslestirilmis T testi kullanildi. Her bir olguda, toplam ateroskleroz yukunun gostergesi olmak uzere karotis arter duvar kalinliklarinin, sagaltim oncesi ve sonrasi icin ayri ayri aritmetik ortalamalari alindi. Bulunan degerler ile eslestirilmis-T testi farklilik istatistigi yapildi. Ortalama karotis arter duvar kalinligi sagaltim oncesi ve sekizinci ay olcumleri arasindaki farkliligi bayanlarda ve baylarda ayri ayri saptayabilmek uzere eslestirilmis T testi farklilik istatistigi kullanildi. Olgularimizda karotis arter duvar kalinliklarindaki gerileme yuzdesi de hesaplandi. Bulunan yeni degerlerle de tanimlayici istatistik yapildi. Plagi olan ve olmayanlarda gerileme yuzdeleri icin ayrica tanimlayici istatistik yapildi. Bay ve bayanlarda gerileme miktarlari ndaki farkliligi arastirmak icin, arastirma kitlesinde plagi olan ve olmayanlar arasi farkliligi arastirmak, plak saptanmayan olgularda bay ve bayan arasinda farklilik olup olmadigini arastirabilmek icin, plak saptanan olgularda bay bayan arasi farkliligi arastirmak uzere Mann-Whitney U farklilik istatistigi yapildi. Tanimlayici ve farklilik istatistiklerinden sonra baginti istatistiklerine gecildi. Olgularimizin sagaltim oncesi duvar kalinliklari ile SKB ve DKB arasindaki baginti arastirildi. Bunun icin Pearson baginti istatistigi kullanildi. Bu baginti, baylarda ve bayanlarda ayrica arastirildi. Bayanlarda Pearson korelasyon testi, baylarda Spearman's korelasyon testi kullanildi. Bulgular Arastirmaya 36-71 yaslarinda (ortalama 54[+ or -]9 yil), 33 bayan ve 16 bay, toplam 49 hasta alindi. Vucut kitle indeksi 22 ile 36 kg/m2 arasi nda degismekte idi (ortalama 29.6[+ or -]3.3 kg/[m.sup.2]). Olgularin AKS ortalama 120.80[+ or -]48.73 mg/dl idi. Diyabetes mellitus tip 2 tanili uc hasta bu ortalamayi yukseltmisti. Bu uc hastanin kan sekerleri haric tutuldu gunda ortalama 109.63[+ or -]19.04 mg/dl'ye dusuyordu. Hastalarin total kolesterol (TK) ortalamasi 220.40[+ or -]43.56 mg/dl, trigliserid ortalamasi 147.73[+ or -]84.12 mg/dl idi. Sirasiyla, DYL ve YYL ortalamalari ise 141.08[+ or -]35.81 mg/dl ve 50.80[+ or -]13.02 mg/dl idi. Hastalarin sagaltim oncesi SKB ortalama 167[+ or -]14 mmHg, DKB ortalamasi ise 102[+ or -]8 mmHg idi. Losartan ile sagaltima baslandiktan sekiz ay sonra ise SKB ortalamasi 139[+ or -]11 mmHg, DKB ortalamasi ise 84[+ or -]8 mmHg'ya dustu (Tablo 1). Calismamizdaki bayanlarin ortalama yasi 52.8[+ or -]8.8 yil, baylarin ortalama yasi 57.5[+ or -]7.6 yil idi. Bayanlarda ve baylarda VKI, AKS, TK, TG, DYL, YYL ve kan basinci ortalamalari Tablo 1'de verilmistir. Bay ve bayan olgular arasinda VKI'nde anlamli farklilik bulundu (p=0.001). Sag eksternal karotis arter sagaltim oncesi duvar kalinligi da aralarinda anlamli farklilik gostermekteydi (p=0.002). Ayrica sagaltim oncesi degerlerden sag ana karotis arter duvar kalinligi (p=0.006) ve sol eksternal karotis arter duvar kalinligi (p=0.003) bay ve bayan olgular arasinda oldukca anlamli farklilik gostermekteydi. Losartan ile sagaltim sonrasinda sekizinci ayda yapilan kontrol olcumlerde sol eksternal karotis arter (p=0.013) ve sol ana karotis arter duvar kalinliklarinda (p=0.028) bay ve bayanlar arasinda anlamli farklilik vardi. Diger degiskenlerde anlamli bir farkli lik bulunmadi. Losartan sagaltimi ile SKB'nda ortalama 167[+ or -]14 mmHg'dan 139[+ or -]11 mmmHg'ya dusus istatistiksel olarak da yuksek derecede anlamli bulundu (p<0.001); DKB ise olgularimizda ortalama 102[+ or -]8 mmHg'dan 84[+ or -]8 mmHg'ya dustu. Bu da istatistiksel acidan oldukca anlamli idi (p<0.001). Olgularin sagaltim oncesinde uc ayri yerden olculen karotis arter duvar kalinliklari ortalamalari sirasiyla, sag internal karotis arterde 0.96[+ or -]0.30 mm, sag eksternal karotis arterde 0.76[+ or -]0.29 mm, sag ana karotis arterde ise 1.06[+ or -]0.32 mm, sol internal karotis arterde 0.96[+ or -]0.29 mm, sol eksternal karotis arterde 0.78[+ or -]0.28 mm, sol ana karotis arterde ise 1.07[+ or -]0.32 mm olarak saptandi. Sagaltim sonrasi nda ortalama duvar kalinliklari, tum olcum yapilan karotis arter ve dallarinda, istatistiksel olarak anlamli duzeyde gerilemis olarak saptandi (Tablo 2, 3). Olgularimizda losartan ile sagaltim oncesi ve sekizinci ay karotis arter B-mod ultrasonograS olcumleri ile karotis arter IMK'nda sagaltim oncesi ve sonrasi degerlerde anlamli farklilik saptandi. Olgularimizda sag internal karotis arter kalinliginda ortalama 0.15[+ or -]0.32 (%95 GA: 0.00-0.24) mm azalma gozlendi. Bu farklilik istatistiksel acidan oldukca anlamliydi (p=0.002). Sag eksternal karotis arter duvar kalinligindaki gerileme ortalama 0.06[+ or -]0.22 mm (%95 GA: 0.00-0.13) olup anlamli bir farklilik gostermekteydi (p=0.049). Sag ana karotis arter duvar kalinliginda ortalama 0.12[+ or -]0.28 mm'lik, (%95 GA: 0.04-0.20) azalma da oldukca anlamli idi (p=0.005). Sol karotis arter duvar kalinliklarindan IKA duvar kalinligi ortalama 0.18[+ or -]0.34 mm, (%95 GA: 0.08-0.27) azaldi, istatistiksel acidan oldukca anlamli bir farklilikti (p= 0.001). Sol EKA duvar kalinligi ise 0,11[+ or -]0,26 mm, (%95 GA: 0.04-0.18) gerileyerek anlamli bir farklilik gosterdi. Sol AKA ise sagaltim sonrasi 0.15[+ or -]0.32 mm, (%95 GA: 0.06-0.24) azalmisti. Bunda da istatistiksel acidan oldukca anlamli bir farklilik belirlendi (p=0.002) (Tablo 2). Bu farkliliklar, bay ve bayanlarda ayri ayri arastirildiginda (Tablo 4, 5) bayanlarda sag IKA, sol IKA, ve sol AKA duvar kalinliklarinda losartan ile sagaltim oncesi ve sekizinci aydaki kontrol ultrasonograS olcumlerinde belirgin derecede azalma (sirasiyla, 0.16 mm, 0.15 mm, 0.15 mm) ve anlamli oranda farklilik saptandi (sirasiyla p<0.001, p=0.009, p=0.002). Diger karotis arter duvar kalinliklarinda azalma mevcuttu, ancak bu azalma anlamli farklilik gostermiyordu. Baylarda da losartan ile sagaltim oncesi ve sekizinci aydaki karotis arter duvar kalinliklari kontrol olcumleri arasindaki farklilik arastirildi. Buna bu·na n. A synthetic rubber made from the polymerization of butadiene and sodium. [Originally a trademark.] Noun 1. gore sag EKA, sag AKA, sol IKA, sol EKA duvar kalinliklarinda sagaltim oncesi ve sonrasi olcumlerde anlamli farklilik saptandi (sirasiyla p=0.004, p=0.016, p=0.015, p=0.035). Hastalarin karotis arter duvar kalinliklari ortalamasinda sagaltim oncesi ve sekizinci aydaki olcumler arasinda 0.13[+ or -]0.23 mm azalma (%95 GA: 0.060.19; p<0.001) saptandi (Tablo 4, 5). Olgulardan 37 kiside (%75.5) plak saptanmazken, 12 kiside (%24.5) cesitli buyukluklerde plaklar gozlendi. Plagi olan ve olmayan olgularda yas, VKI, AKS, TK, TG, DYL, YYL, SKB ve DKB'larinda anlamli bir farklilik saptanmadi. Plagi olmayan bay ve bayanlarin yaslari arasinda (sirasiyla 60.56[+ or -]6.26 ile 51.96[+ or -]8.54) anlamli farklilik bulundu (p=0.008). Ayrica sagaltim sonrasi sol eksternal karotis arter duvar kalinliklarinda da anlamli farklilik vardi (p=0.01). Diger degiskenlerde anlamli farklilik saptanmadi. Olgularin sagaltim oncesi SKB veya DKB ile ortalama karotis arter duvar kalinligi arasinda kayda deger bir baginti yoktu (sirasiyla r=0.122 p=0.403 ve r=0.032 p=0.828). Bu baginti istatistigi, bay ve bayanlarda ayri ayri yapildiginda da benzer sonuc goruldu. Olgularimizin karotis arter duvar kalinliklarinda losartan sagaltimi ile gerileme yuzdeleri sirasiyla sag IKA'de %9.39, sag EKA'de %2.43, sag AKA'de %6.06 iken sol IKA'de %12.04, sol EKA'de %7.43, sol AKA'de %7.32 idi. Karotis arter duvar kalinliklari ortalamasindaki gerileme yuzdesi ise %9.39 bulundu (Tablo 5). Bay ve bayanlarda karotis arter duvar kalinliklarinin gerileme yuzdeleri arasinda anlamli farklilik saptanmadi (Tablo 5). Plagi olan ve olmayanlar arasinda ise sag EKA (p=0.006), sol IKA (p=0.05), sol EKA'de (p=0.006) gerileme yuzdeleri anlamli olarak farkliydi. Bu anlamli farklilik tum duvarlarin ortalama kali nliginin gerileme yuzdelerinde de (p=0.006) gozlenmekteydi (Tablo 6). Tartisma Calismamizda, hipertansif hastalarda kullanilan AT1 reseptor blokeri losartanin karotis arter intima-media kalinligina etkisini arastirdik. Bunun icin kirk dokuz yeni hipertansif hastada, karotis arter ve dallarinda duvar kalinliklari olculup antihipertansif olarak Losartan sagaltimina baslandi. Sekizinci ayda duvar kalinlik olcumleri yinelendi. Olgularda kan basinclari ile karotis arter intima media kalinliklarinda, ortalama olarak, bayanlarda 0.10[+ or -]0.19 mm (p=0.004), baylarda 0.18[+ or -]0.29 mm (p=0.007) ve tum olgularda 0.13[+ or -]0.23 mm (p<0.001) olarak anlamli gerileme olustugu saptandi. Yapilan hayvan deneylerinin sonuclari RAAS'nin ateroskleroz olusumundaki onemini vurgulamaktadir. Anjiyotensin donusturucu enzim inhibitoru verilen, kolesterolden zengin diyetle beslenmis tavsanlar, spontan hipertansif ratlar (12-14) ve cynomolgus maymunlarinda (Macaca Macaca genus of Old World monkeys very popular in zoos and for some aspects of human laboratory medicine. See macaque. fascicularis) (15, 16) antiaterojenik etkiler gozlenmistir. Aortik lezyon alaninda gerileme, intimal intimal pertaining to or emanating from vascular intima. intimal bodies irregular mineralized masses covered by endothelium and protruding into the lumen of small arteries and arterioles of horses, especially in the intestinal kalinlasmada azalma saptanmistir. Anjiyotensin-II reseptor blokeri (ARB) ile yapilan hayvan calismalari da benzer bulgularla sonuclanmis ve aterosklerozun ilerlemesinin onlenmesinde ARB'leri etkili bulunmustur (17, 18). Bu konuda sunulan son iki arastirmada losartan ve olmesartan kullanilmistir. Strawn ve ark.lari la·ri n. pl. lari See Table at currency. [Georgian.] Noun 1. lari - the basic unit of money in Georgia Georgian monetary unit - monetary unit in Georgia (19) diyetle hiperlipidemik yapilmis erkek cynomolgus maymunlarina losartan vermisler ve damar yapisi olarak insanlarinkine cok benzedigi icin secildiklerini de ayrica belirtmislerdir. Miyazaki ve ark.lari (20) ise cynomolgus maymunlarinda olmesartan kullanmislardir. Her iki arastirmanin da yagli cizgilenmede belirgin azalma, aterosklerotik lezyon bolgesinde ve aort IMK'inda belirgin gerileme ile sonuclandigi bildirilmistir. Insanlarda aterosklerozun arastirilmasi tip ahlaki uyarinca histoloji duzeyine inememektedir. Aterosklerozun saptanmasina yonelik girisimsel ve girisimsel olmayan yontemler gunumuzde yaygin olarak kullanilmaktadir. American Heart Association American Heart Association (AHA), n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities. taraS ndan aterosklerozun belirlenmesinde en yararli yontem olarak karotis arter IMK olcumu onerilmektedir (21). B-mod ultrasonograS ile karotis arter IMK olculebilmektedir. Karotis arter IMK'nin kardiyovaskuler hastalik oykusu olmayan hastalarda miyokard infarktusu ve inme olasiligi ile dogru oranti gosterdigini destekleyen bircok ileriye donuk epidemiyolojik calisma vardir. Bunlardan ikisi, Atherosclerosis Risk in Communities (ARIC ARIC Atherosclerosis Risk in Communities (Study) ARIC Asia Recovery Information Center ARIC Alliance for Rational Intercarrier Compensation ARIC Appliance Recycling Information Center ARIC Acid Rain Information Clearinghouse ) Study (22) ve Cardiovascular Health Study (CHS (Cylinder Head Sector) An earlier method of addressing a hard disk by referencing all three physical elements of the drive. It was superseded by logical block addressing (see LBA). ) (23), ABD'de buyuk kitlelerde yapi lmistir. Atherosclerosis Risk in Communities calismasi 19871989 yillari arasinda ABD'nin dort ayri bolgesinde 5-65 yas arasi 15.792 kisiye bazal karotis B mod USG (UNIX Systems Group) The division within Novell that was responsible for UnixWare. See USL. ile IMK olculmus ve 4-7 yil arayla olcumler yinelenmistir. Karotis arter IMK'ndaki artis, koroner arter hastaligi olasiliginda artma ile iliskili bulunmustur. Cardiovascular Health Study 1988 yilinda baslatilmis, 65 yas ve altindaki 4476 kiside, karotis arter IMK ile miyokard infarktusu ve inme arasindaki iliski arastirilmistir. Yaklasik 6 yillik izlem sonrasi karotis arter IMK olcumleri kardiyovaskuler olaylarla iliskili bulunmustur. Cahn ve ark.nin (24) 152 koroner arter hastasinda yapmis oldu gu arastirmada, cesitli laboratuvar incelemeleri ve karotis arter ultrasonograSsi uygulanan hastalar 6-11 ay izlenmis. Bu sure icinde 22 damarsal olay (miyokard infarktusu, gecici iskemik atak, inme, koroner anjiyoplasti, vb) gelistigini saptamislar. Girisimsel olmayan yontemle olculen karotis aterosklerozun koroner arter hastalarinda prognostik onem tasidigi sonucunu ortaya cikarmislar (24). Bir baska arastirmada ise AKA IMK, koroner arter hastalari nda miyokard akim kapasitesi ile bagintili bulunmus ve karotis arter IMK olcumunun, koroner aterosklerozunun, girisimsel olmayan bir belirteci olarak onemi vurgulanmistir (25). Bu verilerin isigi altinda calismamizda ateroskleroz belirteci olarak karotis arter IMK olcumunun kullanilmasi yeglendi. Karotis arter IMK'na losartan'in etkisinin olup olmadigi belirlenmeye calisildi. Multicenter American Research Trial With Cilazapril After Angioplasty angioplasty (ăn`jēōplăs'tē), any surgical repair of a blood vessel, especially balloon angioplasty or percutaneous transluminal coronary angioplasty, a treatment of coronary artery disease. to Prevent Transluminal transluminal /trans·lu·mi·nal/ (trans-loo´mi-n'l) through or across a lumen, particularly of a blood vessel. trans·lu·min·al adj. Passing or occurring across a lumen. Coronary Obstruction obstruction /ob·struc·tion/ (ob-struk´shun) 1. the act of blocking or clogging. 2. block; occlusion; the state or condition of being clogged.obstruc´tive ob·struc·tion n. and Restenosis restenosis /re·ste·no·sis/ (re?ste-no´sis) recurrent stenosis, especially of a cardiac valve after surgical correction of the primary condition.restenot´ic re·ste·no·sis n. (MARCATOR) ve Multicenter European Research trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) arastirmalari birbirine benzer yapidadir. MARCATOR grubu 1400 hastada calismis ve silazapril altinci ayin a·yin n. The 16th letter of the Hebrew alphabet. See Table at alphabet. [Hebrew 'ayin, eye, ayin; see sonunda restenoza etki etmeyerek basarisizli kla sonuclanmis (26). MERCATOR grubu ise 653 hastada alti ayli k silazapril kullanimi sonrasi klinik ve anjiyograSk gerileme gozlenmemis (27). Quinapril Ischemic Ischemic An inadequate supply of blood to a part of the body, caused by partial or total blockage of an artery. Mentioned in: Antiangiogenic Therapy, Subarachnoid Hemorrhage, Ventricular Fibrillation ischemic Event Trial (QUIET) ise 1750 hastanin katildigi bir arastirma olup uc yillik gozlem sonrasi klinik olarak ve anjiyograSk restenoz sikliginda plasebo ve quinapril arasinda fark saptanmamis (28). Hayvan ve insan arastirma sonuclari ndaki bu tutarsizlik ilac dozlarinda yetersizlik, aterosklerotik lezyon olcumunde teknolojik yetersizlik, hasta sayisinin fazla olmasi sebebiyle takip zorlugu ve beraberinde hasta uyumunda bozukluk ile iliskili olabilir diye dusunulmus. Study to Evaluate Carotid Ultrasound carotid ultrasound Imaging The use of ultrasound to evaluate blood flow through the carotid arteries in the neck in Pts at risk of CVAs or TIAs changes in patients treated with Ramipril and vitamin E vitamin E or tocopherol Fat-soluble organic compound found principally in certain plant oils and leaves of green vegetables. Vitamin E acts as an antioxidant in body tissues and may prolong life by slowing oxidative destruction of membranes. (SECURE) arastirmasi, insanlarda, aterosklerozun ilerlemesinde ACE inhibisyonunun etkili olabilecegini gosteren ilk arastirmadir. Arastirmaya 55 yas ve ustunde 732 yuksek kardiyovaskuler riskli hasta alinmis. Aterosklerozun ilerlemesi B-mod karotis arter ultrasonograSsi olcumleri ile izlenmis. Intima-media kalinliklari, onceden belirlenmis 12 kesitte olculmus ve hastalar yaklasik 4.5 yil izlenmis. Sonucunda IMK ilerlemesinde belirgin gerileme saptanmis. Bu gerilemenin tek basina kan basincindaki dusmeyle aciklanamayacagi belirtilmistir (29). Calismamizda, sag ve sol karotis arterde IMK olcumu, her olguda AKA, IKA ve EKA olmak uzere 3 ayri arterde yapildi. Losartan ile sagaltim sonrasi olculen tum karotis arter IMK'larinda anlamli gerileme gozlendi. Arastirmamizda sekiz ay kadar izledigimiz hastalarimizdan sadece ucu diyabetik idi. Losartan kullanimi sonrasi sag AKA IMK'nda 0.12[+ or -]0.28 mm (p=0.005), sol AKA IMK'nda ise 0.15[+ or -]0.32 mm'lik (p=0.002) anlamli gerileme saptandi. Hosomi ve ark.lari (30) Tip 2 diyabetik 98 hastada ACE inhibitoru enalaprilin AKA IMK'ndaki ilerlemeye etkisini arastirmislar. Iki yil izlemi yapilan hastalarin sag ve sol AKA IMK'nda yillik 0.010[+ or -]0.004 mm gerileme gozlemisler. Uzun sureli kullanimlarda enalaprilin AKA IMK ilerlemesini yavaslattigini belirtmisler. EUropean trial on Reduction Of cardiac events cardiac event Coronary event Cardiology Any severe or acute cardiovascular condition including acute MI, unstable angina, or cardiac mortality with Perindopril in stable coronary Artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. (EUROPA) haSf-orta hipertansif ve dusuk riskli hastalarda RAAS antagonizmasinin ateroskleroza etkisini, ACE inihibitoru perindoprilin kullanildigi klinik bir arastirmayla gostermistir. Dusuk riskli 12218stabil koroner arter hastasi arastirmaya alinmis. Bunlardan 6110'u 3 yil sureyle perindopril kullanmis. Tum kardiyovaskuler olaylarda plaseboya gore oldukca anlamli bir azalma saptanmistir (31). Losartan Vascular Regression Study (LAARS), ARB'lerinin IMK'na etkisini arastiran ilk buyuk capli arastirmadir. Iki yil boyunca AKA IMK olculen hipertansif hastalarda losartan ve atenololun etkileri karsilastirilmis. Cift kor, randomize ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. , kontrollu bu calismaya 35-65 yas arasi 280 haSf-orta hipertansiyonlu hasta alinmis. Sag ve sol AKA IMK'lari 0.8-1.5 mm arasinda bulunmus. Yuz kir iki hasta losartan, 138 hasta atenolol atenolol /aten·o·lol/ (ah-ten´ah-lol) a cardioselective ß used in the treatment of hypertension and chronic angina pectoris and the prophylaxis and treatment of myocardial infarction and cardiac arrhythmias. ile sagaltim yapilmis. Iki yilin sonunda, AKA ortalama IMK'nda belirgin gerileme saptanmis. Losartan ile yillik gerilemenin 0.038[+ or -]0.004 mm (p=0.001), atenolol ile yillik gerilemenin 0.037[+ or -]0.004 mm (p=0.001) oldugu gorulmus. Arastirmada losartanin AT-II antagonizmasi ile vaskuler hipertroSnin erken safhalarini geriletebilecegi, bunun da AKA IMK'ndaki gerileme ile gosterildigi belirtilmis (32). Arastirmamiza katilan 49 olgunun sekiz aylik losartan kullanimi sonrasinda sag AKA 0.12[+ or -]0.28 mm (p=0.005), sol AKA IMK'nda ise 0.15[+ or -]0.32 mm'lik (p=0.002) gerileme gozlendi. Ancak LAARS sonuclarina gore losartan ve atenolol arasinda AKA IMK'nda gerileme ile ilgili anlamli bir istatistiksel farklilik saptanmamistir. Losartan Vascular Regression Study'de ve bu arastirmamizda, losartanin kan basincini duzenleyerek karotis arter IMK'ni gerilettigi de dusunulebilir. Bu kanit ancak histolojik duzeyde bir calismayla elde edilebilir. Multicenter Isradipine Diuretic diuretic (dī'yərĕt`ĭk), drug used to increase urine formation and output. Diuretics are prescribed for the treatment of edema (the accumulation of excess fluids in the tissues of the body), which is often the result of underlying Atherosclerosis Study (MIDAS Midas (mī`dəs), in Greek mythology, king of Phrygia. Because he befriended Silenus, the oldest of the satyrs, Dionysus granted him the power to turn everything into gold by touch. ) (33), isradipin ve hidroklorotiyazidin kan basincini belirgin olarak dusurdugunu ancak IMK'nda ilerlemenin devam ettigini gostermis. Verapamil verapamil /ve·rap·a·mil/ (ve-rap´ah-mil) a calcium channel blocker that dilates coronary arteries and decreases myocardial oxygen demand, used as the hydrochloride salt in the treatment of angina pectoris and of hypertension and the in Hypertension and Atherosclerosis Study (VHAS) (34) verapamil ve klortalidonun kan basincinda belirgin dusme gostermesine ragmen IMK'ni etkilemedigini saptamis. International Nifedipine nifedipine /ni·fed·i·pine/ (ni-fed´i-pen) a calcium channel blocking agent used as a coronary vasodilator in the treatment of coronary insufficiency and angina pectoris; also used in the treatment of hypertension. GITS GITS Ghost in the Shell (Anime movie based on the Manga by Masamune Shirow) GITS Government Information Technology Services GITS Government Information Technology Services Board GITS Gastro-Intestinal Therapeutic System (Goal In hypertension Treatment Study) sonuclarinda ise nifedipin kan basincinda gerileme ile birlikte IMK'nda da ilerlemede yavaslama gozlenmis, oysa amilorid-hidroklorotiazid birlikte verildiginde kan basinci dusmesine ragmen IMK ilerlemesinde hicbir yavaslama olmamis (35). Bu verilere dayanarak IMK'ndaki degisikliklerin kan basincindaki dusmeden bagimsiz oldu gu dusunulebilir. Arastirmamizda sag ve sol IKA, EKA, AKA IMK'larina ek olarak ortalama IMK'larinda da losartan ile sagaltim oncesi ve sekizinci aydaki olcumler arasinda belirgin gerileme goruldu. Bu gerilemeler istatistiksel acidan oldukca anlamliydi. Bir antihipertansif olan losartani n olgularimizin sistolik ve diyastolik kan basinclarindaki dusme ile sag ve sol IKA, EKA, AKA ve ortalama IMK'lari arasinda zayif ve istatistiksel olarak anlam tasimayan baginti saptandi. Bu sonuc bize losartanin antihipertansif etkinin otesinde farkli bir yoldan karotis arter intima-media kalinliginda gerileme sagladigini dusundurmektedir. Bu farkli yol ateroskleroz ve RAAS arasinda kopru niteli gindeki AT-II ve onun aterosklerotik etkilerinden sorumlu AT1 reseptorleriyle iliskili olabilir. Losartanin AT1 reseptorlerini baskilayarak AT-II antagonizmasi ile olgularimizda aterosklerozun erken evrelerinde ilerlemeyi durdurdugu ve hatta gerilettigi dusunulebilir. Irbesartan'la yapilmis bir arastirmada 33 stabil koroner arter hastasinda 6 aylik irbesartan sagaltimi oncesi ve sonrasinda yangi belirtecleri olan tumor tumor: see neoplasm. nekrozis faktor alfa (TNF TNF abbr. tumor necrosis factor TNF, n an abbreviation for tumor necrosis f alfa), "vascular cell adhession molecule-1" (VCAM-1) duzeyleri olculmus ve irbesartanin TNF alfa ve VCAM-1 uzerinde belirgin azaltici etkisi saptanmis. Aterosklerozun yangisal bir surec oldugundan hareketle irbesartani n AT1 reseptor blokaji ile AT-II antagonizmasi yaparak erken aterosklerozda bu sureci geciktirebilecegi one surulmus (36). Baska bir arastirmada ise apolipoprotein E apolipoprotein E A 34-kD cholesterol-binding glycoprotein, which comprises 15% of VLDL; apoE maps to chromosome 19, is secreted by macrophages that mediate the uptake of lipoproteins–VLDL, HDL, LDL and cholesterol esters into cells via distinct binding fareler uzerinde calisilmis ve irbesartanin makrofaj birikimi ve sitokin sunumunu engelleyerek insamasyonda baskilayici rol aldigini ve bu sekilde aterosklerotik lezyonlari geriletebilecegini belirtmisler (37). Heras ve ark.lari (38); aterosklerotik tavsanlarda ARB valsartanin intimal lezyonlari anlamli oranda gerilettigi ve damar lumen alanini artirdigini gozlemlemisler. Antihipertansif etkilerinin yaninda ARB'lerinin aterosklerozun geriletilmesinde onemli rol oynayabilecegine dikkati cekmislerdir (38). Intima-media kalinligindaki ilerlemenin yasla birlikte artis gosterdigi dusunulmektedir (39). Stensland-Bugge ve ark.lari (39) karotis ateroskleroz ile cinsiyet iliskisini arastirmislardir. Norvec'te 1994-1995 yillari arasinda 25-84 yaslari arasinda toplam 6408 kiside yaptiklari arastirmada B-mod ultrasonograS kullanilarak AKA duvari ve bifurkasyonundan olcumler yapilmis. Yas ile birlikte her iki cinste de IMK'nda artis olmasina karsin, baylarda bayanlara gore daha fazla miktarda bir ilerleme gozlenmis. Bayan-bay arasi AKA IMK degerlerinde 0.07 mm anlamli bir farklilik saptanmis (p<0.0001). Cinsiyete bagli olarak ortaya cikan bu farkliligi aterosklerozun cinsiyetle iliskisinden cok lumen capi gibi Szyolojik cinsiyet farkliliklarina baglamislar. Calismamizda, bay-bayan olgularin sag AKA, sag EKA ve sol EKA IMK'lari arasinda anlamli farklilik belirlendi (p=0.006, p=0.002, p=0.003). Losartan ile sagaltim sonrasinda ise yalnizca sol AKA ve sol EKA IMK'larinda anlamli farklilik saptandi (p=0.028, p=0.013). Bayanlarda sag IKA, sol IKA, sol AKA IMK'larinda istatistiksel olarak anlamli gerileme gozlendi (p<0.001, p=0.009, p=0.002). Baylarda losartan kullanimi sonrasi sag EKA, sag AKA, sol IKA, sol EKA IMK'larinda anlamli farklilik saptandi (p=0.004, p=0.016, p=0.015, p=0.035). Bay ve bayanlarda ayri ayri incelendi ginde losartan kullanimi sonrasi karotis arter IMK'larinda anlamli bir gerileme gorulmesine ragmen bay ve bayan arasinda anlamli bir farklilik gozlenmedi. Sonuclarimizin, Stensland-Bugge ve ark.nin (39) bulgularina benzer olmadigi gorulmektedir. Sag AKA'de ortalama gerileme yuzdesi %6.06 olup bay ve bayanlar arasi nda anlamli bir farklilik gostermemekteydi (p=0.099). Sol AKA IMK gerileme yuzdesi ise ortalama %7.32 idi ve bay-bayan arasinda anlamli bir farklilik gostermiyordu. Bay-bayan arasi karotis arter IMK'larinda anlamli bir fark saptamayisimiz bize cinsiyete bagli Szyolojik degisikliklerin antiaterosklerotik sagaltimi etkilemeyebilecegini dusundurebilir. Kitamura ve ark.lari (40) yasli Japon baylarda karotis aterosklerozu arastirmislar. Arastirmaya 60-74 yaslari arasinda 1129 bay kati lmis. Ana karotis arter ve IKA olculmus ve sonuclar yukarida bah settigimiz iki buyuk epidemiyolojik arastirmadan biri olan CHS ile karsilastirilmis. Cardiovascular Health Study, beyaz baylar icin en yuksek IMK AKA'de 1.05 mm, IKA'de ise 1.67 mm olarak belirtmis. Kitamura ve ark.nin (40) arastirmasinda ise en yuksek IMK AKA icin 0.86 mm, IKA icin 1.05 mm bulunmus. Daha yasli bir toplulukta daha dusuk IMK saptanmis. Bu sonuclara dayanarak yasli Japon baylarda karotis aterosklerozun cok daha az gorulebilecegini dusunmusler. Arastirma kitlemizde toplam 49 olgu vardi. Bunlardan 16'si bay, 33'u bayandi. Bayanlarda en yuksek IMK sag AKA icin 1.6 mm, sag IKA icin 1.6 mm, sol AKA icin 1.7 mm, sol IKA icin 1.6 mm saptandi. Baylarda ise en yuksek IMK sag AKA'de 1.6 mm, sag IKA'de 2 mm, sol AKA'de 2.1 mm, sag IKA'de 1.7 mm olarak olculdu. Arastirma kitlemizde ortalama yas 52 yil olup CHS yas ortalamasina yakindi. En yuksek IMK degerlerimiz CHS'ye gore oldukca fazla idi. Buna gore Aydin ilini ornekledigimizden yola cikarak Amerika'ya ve Japonya'ya gore ateroskleroz tehlikemizin daha fazla oldugu soylenebilir. Ancak CHS 1988-1994 yillari arasinda yapilmis bir epidemiyolojik arastirma olup gunumuzden 10 yil oncesinin verilerini bildirmektedir. Sonuc Sonuc olarak; losartan kullanimi sonrasi, olgularin sag ve sol AKA, IKA, ve EKA olmak uzere uc ayri bolgede olculen IMK'larinda anlamli gerileme, her iki arterin IMK'lari ortalamasinda ise oldukca anlamli gerileme gozlendi. Intima media kalinliklarindaki gerileme bay-bayan arasi farklilik gostermedi. Cinsiyet ateroskleroz icin bir tehlike etkenidir ve altmis yasina dek baylarda kadinlardan daha sik aterosklerotik klinik olay ortaya cikar. Losartan bu tehlike etkeninden etkilenmeksizin aterogenezi baskilayici isleve sahip gorunmektedir. Sonuclarimiz tibbi yazincadaki (literatur) varsayimlar ve ongoruleri destekler nitelikte olup losartanin antihipertansif etkisinin yani sira, aterogenezdeki cesitli yolaklar uzerine etkiyle, aterogenezi durdurabilecegini ve hatta geriletebilecegini dusundurmektedir. Dolayisiyla, losartanin hipertansiyondan ayri olarak, fazla sayida ateroskleroz tehlike etkeni tasiyan bireylerde, erken yaslarda aterosklerozdan korunma amaci ile de kullanilmasinin onerilmesi ve tartisilmasi gerektigi kanisindayiz. Not: Bu calissmamizin sonuclari "Second Mediterranean Meeting on Hypertension and Atherosclerosis. March 30-April 3 2005, Antalya, Turkiye" kongresinde sozlu bildiri olarak sunulmusstur. Kaynaklar (1.) Falk E, Fuster V. Aterogenez ve belirleyicileri. In: Fuster V, Alexander RW ve O'Rourke RA, editorler. Hurst's the Heart (Turkce ceviri), 10. baski. Istanbul: AND yayincilik; 2002. s. 1065-93. (2.) Libby P. Prevention and treatment of atherosclerosis. 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Cell biology Cell biology The study of the activities, functions, properties, and structures of cells. Cells were discovered in the middle of the seventeenth century after the microscope was invented. and genetics of angiotensin in cardiovascular disease Cardiovascular disease Disease that affects the heart and blood vessels. Mentioned in: Lipoproteins Test cardiovascular disease . J Hypertens 1994; 12: 3-10. (9.) Sonmez H M, Basak O, Camci C, Baltaci R, Karazeybek H S, Yazgan F, at al. The epidemiology epidemiology, field of medicine concerned with the study of epidemics, outbreaks of disease that affect large numbers of people. Epidemiologists, using sophisticated statistical analyses, field investigations, and complex laboratory techniques, investigate the cause of elevated blood pressure as an estimate for hypertension in Aydin, Turkey. J Hum hum (hum) a low, steady, prolonged sound. venous hum a continuous blowing, singing, or humming murmur heard on auscultation over the right jugular vein in the sitting or erect position; it is Hypert 1999; 13: 399-404. (10.) Oparil S. Arterial arterial /ar·te·ri·al/ (-al) pertaining to an artery or to the arteries. ar·te·ri·al adj. 1. Of or relating to one or more arteries or to the entire system of arteries. 2. Hypertension. In: Goldman L, Bennett J, editors. Cecil Textbook of Medicine. 21st edition. Philadelphia, Pennsylvania: WB Saunders Company; 2000. p. 258-73. (11.) Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh repot Verb 1. repot - put in a new, usually larger, pot; "The plant had grown and had to be repotted" pot - plant in a pot; "He potted the palm" of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure: JNC VII. JAMA JAMA abbr. 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Antiatherogenic effect of captopril captopril /cap·to·pril/ (kap´to-pril) an angiotensin-converting enzyme inhibitor used in the treatment of hypertension, congestive heart failure, and post–myocardial infarction left ventricular dysfunction. in the Watanabe heritable her·i·ta·ble adj. 1. Capable of being passed from one generation to the next; hereditary. 2. Capable of inheriting or taking by inheritance. hyperlipidemic rabbit. Hypertension 1990; 15: 327-31. (14.) Hernandez A, Barberi L, Ballerio R, Testini A, Ferioli R, Bolla M, et al. Delapril slows the progression of atherosclerosis and maintains endothelial endothelial /en·do·the·li·al/ (-the´le-al) pertaining to or made up of endothelium. Endothelial A layer of cells that lines the inside of certain body cavities, for example, blood vessels. function in cholesterol-fed rabbits. Atherosclerosis 1998; 137: 71-6. (15.) Song K, Shiota N, Takai S, Takashima H, Iwasaki H, Kim S, et al. Induction of angiotensin converting enzyme and angiotensin II angiotensin II n. An octapeptide that is a potent vasopressor and a powerful stimulus for production and release of aldosterone from the adrenal cortex. receptors in the atherosclerotic atherosclerotic pertaining to atherosclerosis. aorta of high cholesterol Cholesterol, High Definition Cholesterol is a fatty substance found in animal tissue and is an important component to the human body. It is manufactured in the liver and carried throughout the body in the bloodstream. fed cynomolgus monkeys. Atheroclerosis 1998; 138: 171-82. (16.) Miyazaki M, Sakonjo H, Takai S. 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Inhibitory effect of an angiotensin II type 1 receptor antagonist on growth of vascular smooth muscle Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels. Vascular smooth muscle contracts or relaxes to both change the volume of blood vessels and the local blood pressure, a mechanism that cells from spontaneously hypertensive rats. J Cardiovasc Pharmacol 1996; 27: 58-63. (18.) Hope S, Brecher P, Chobanion AV. Comparison of the effects of AT1 receptor blockade blockade, use of naval forces to cut off maritime communication and supply. Blockades may be used to prevent shipping from reaching enemy ports, or they may serve purposes of coercion. The term is rarely applied to land sieges. and angiotensin converting enzyme inhibition on atherosclerosis. Am J Hypertens 1999; 12: 28-34. (19.) Strawn WB, Chappell MC, Dean RH, Kivlighn S, Ferrario CM. 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To put or bring into causal, complementary, parallel, or reciprocal relation. 2. with myocardial myocardial /myo·car·di·al/ (-kahr´de-al) pertaining to the muscular tissue of the heart. myocardial pertaining to the muscular tissue of the heart (the myocardium). sow reserve in patients with coronary artery disease: a useful non-invasive indicator of coronary atherosclerosis. Int J Cardiol 2004; 93: 131-6. (26.) Berger PB, Holmes DR, Ohman EM, O' Hanesian MA, Murphy JG, Schwartz RS, et al. Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty balloon angioplasty: see under angioplasty. of occluded versus nonoccluded coronary arteries Coronary arteries The two main arteries that provide blood to the heart. The coronary arteries surround the heart like a crown, coming out of the aorta, arching down over the top of the heart, and dividing into two branches. . 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In the civil law this term is used to signify the injury suffered, in consequence of inequality of situation, by one who does not receive a full equivalent for what he gives in a commutative contract. 2. size, chemokine chemokine /che·mo·kine/ (ke´mo-kin) any of a group of low molecular weight cytokines identified on the basis of their ability to induce chemotaxis or chemokinesis in leukocytes (or in particular populations of leukocytes) in inflammation. expression, and macrophage macrophage /mac·ro·phage/ (mak´ro-faj) any of the large, mononuclear, highly phagocytic cells derived from monocytes that occur in the walls of blood vessels (adventitial cells) and in loose connective tissue (histiocytes, phagocytic accumulation in apolipoprotein apolipoprotein /apo·lipo·pro·tein/ (ap?o-lip?o-pro´ten) any of the protein constituents of lipoproteins, grouped by function in four classes, A, B, C, and E. ap·o·lip·o·pro·tein n. E-deScient mice. J Cardiovasc Pharmacol 2001; 38: 395-405. 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Tablo 1. Arastima kitlemizdeki tanimlayici bulgular
Tum katilimcilarda
Parametreler En En
dusuk yuksek Ortalama [+ or -] ss
Yasi, yil 36 71 54 [+ or -] 9
VKI, [kgm.sup.2] 22 36 29.6 [+ or -] 3.3
AKS, mg 74 335 120.80 [+ or -] 48.73
TK, mg 150 386 220.04 [+ or -] 43.56
TG, mg 30 86 50.80 [+ or -] 13.02
YDL, mg 48 425 147.70 [+ or -] 84.12
DYL, mg 78 222 135.15 [+ or -] 35.81
SKB1, mmHg 145 200 166.63 [+ or -] 14.27
SKB2, mmHg 120 180 150.71 [+ or -] 14.43
SKB3, mmHg 110 160 138.78 [+ or -] 10.68
DKB1, mmHg 80 120 102.04 [+ or -] 8.29
DKB2, mmHg 80 110 90.71 [+ or -] 8.60
DKB3, mmHg 65 100 84.29 [+ or -] 8.04
Bayanlarda
Parametreler En En
dusuk yuksek Ortalama [+ or -] ss
Yasi, yil 36 69 52.8 [+ or -] 8.8
VKl, [kgm.sup.2] 22 36 30.52 [+ or -] 3.07
AKS, mg 74 335 126.24 [+ or -] 57.88
TK, mg 150 386 222.15 [+ or -] 48.62
TG, mg 48 347 136.48 [+ or -] 64.46
YDL, mg 30 86 53.15 [+ or -] 14.77
DYL, mg 78 280 140.55 [+ or -] 42.91
SKB1, mmHg 145 200 166.21 [+ or -] 14.25
SKB2, mmHg 120 180 151.06 [+ or -] 15.25
SKB3, mmHg 110 160 138.48 [+ or -] 11.21
DKB1, mmHg 80 120 101.36 [+ or -] 8.41
DKB2, mmHg 80 110 90.30 [+ or -] 8.56
DKB3, mmHg 65 100 82.73 [+ or -] 8.21
Baylarda p *
Parametreler En En
dusuk yuksek Ortalama [+ or -] ss Bay-Bayan
Yasi, yil 42 71 57.5 [+ or -] 7.6 AD
VKl, [kgm.sup.2] 25 36 27.62 [+ or -] 2.96 AD
AKS, mg 88 138 109.56 [+ or -] 15.83 AD
TK, mg 176 289 215.69 [+ or -] 31.60 AD
TG, mg 56 364 158.44 [+ or -] 93.02 AD
YDL, mg 35 57 45.94 [+ or -] 6.28 AD
DYL, mg 95 222 142.19 [+ or -] 33.62 AD
SKB1, mmHg 150 200 167.50 [+ or -] 14.72 AD
SKB2, mmHg 120 170 150.00 [+ or -] 13.04 AD
SKB3, mmHg 120 150 139.38 [+ or -] 9.81 AD
DKB1, mmHg 95 120 103.44 [+ or -] 8.11 AD
DKB2, mmHg 80 110 91.56 [+ or -] 8.89 AD
DKB3, mmHg 75 100 87.50 [+ or -] 6.83 AD
Eslestirilmemis Student t te sti
AD--anlamli degil, AKS--aclik kan sekeri, DKB--diyastolik kan basinci,
(1, 2, ve 3 rakamlari, sirasiyla ilk, orta ve ucuncu olcumleri
gostermektedir), DYL--dusuk yogunluklu lipoprotein, SKB--sistolik kan
basinci, ss--standart sapma, TG--trigliserid, TK--total kolesterol,
VKI-vucut kitle indeksi, YYL-Yuksek yogunluklu lipoprotein
Tablo 2. Arastima kitlemizde losartan ile sagaltim oncesi ve sekizinci
aydaki IMK olcum bulgulari ve farklilik istatistikleri
Parametreler Ilk olcum Ikinci olcum
0rtalama [+ or -] ss, mm 0rtalama [+ or -] ss, mm
Sag IKA 0.96 [+ or -] 0.30 0.81 [+ or -] 0.20
Sag EKA 0.76 [+ or -] 0.29 0.69 [+ or -] 0.22
Sag AKA 1.06 [+ or -] 0.32 0.94 [+ or -] 0.24
Sol IKA 0.96 [+ or -] 0.29 0.78 [+ or -] 0.22
Sol EKA 0.78 [+ or -] 0.28 0.68 [+ or -] 0.2
Sol AKA 1.07 [+ or -] 0.32 0.92 [+ or -] 0.23
Parametreler Ortalama
gerileme [+ or -] ss, mm p *
Sag IKA 0.15 [+ or -] 0.32 0.002
Sag EKA 0.06 [+ or -] 0.22 0.049
Sag AKA 0.12 [+ or -] 0.28 0.005
Sol IKA 0.18 [+ or -] 0.34 0.001
Sol EKA 0.11 [+ or -] 0.26 0.005
Sol AKA 0.15 [+ or -] 0.32 0.002
*--Eslestirilmis-t testi sonuclari.
AKA--ana karotis arter, EKA--eksternal karotis arter, IKA--internal
karotis arter, IMK--intima media kalinligi, ss--standart sapma
Tablo 3. Bayanlarda ve baylarda losartan ile sagaltim oncesi ve
sekizinci aydaki karotis arter IMK olcumleri (1 ve 2'inci olcumler)
ile farklilik istatistikleri
Parametreler Bayanlarda (s=33) p
Sag IKA 1, mm 0.93 [+ or -] 0.27; 0.90 (0.4-1.6) 0.000
Sag IKA 2, mm 0.78 [+ or -] 0.19; 0.80 (0.4-1.2)
Sag EKA 1, mm 0.66 [+ or -] 0.23; 0.60 (0.3-1.4) AD
Sag EKA 2, mm 0.65 [+ or -] 0.19; 0.70 (0.3-1.1)
Sag AKA 1, mm 0.97 [+ or -] 0.29; 0.90 (0.4-1.6) AD
Sag AKA 2, mm 0.90 [+ or -] 0.25; 0.90 (0.4-1.4)
Sol IKA 1, mm 0.93 [+ or -] 0.26; 0.90 (0.5-1.6) 0.009
Sol IKA 2, mm 0.78 [+ or -] 0.22; 0.80 (0.4-1.3)
Sol EKA 1, mm 0.69 [+ or -] 0.22; 0.70 (0.3-1.2) AD
Sol EKA 2, mm 0.62 [+ or -] 0.17; 0.60 (0.4-1.0)
Sol AKA 1, mm 1.02 [+ or -] 0.28; 1.10 (0.5-1.7) 0.002
Sol AKA 2, mm 0.87 [+ or -] 0.20; 0.90. (0.4-1.4)
Parametreler Baylarda (s=16) p *
Sag IKA 1, mm 1.00 [+ or -] 0.35; 1.00 (0.6-2.0) 0.218
Sag IKA 2, mm 0.87 [+ or -] 0.20; 0.85 (0.4-1.2)
Sag EKA 1, mm 0.95 [+ or -] 0.30; 0.95 (0.5-1.4) 0.004
Sag EKA 2, mm 0.79 [+ or -] 0.26; 0.70 (0.5-1.4)
Sag AKA 1, mm 1.23 [+ or -] 0.30; 1.25 (0.5-1.6) 0.016
Sag AKA 2, mm 1.01 [+ or -] 0.21; 1.00 (0.6-1.4)
Sol IKA 1, mm 1.03 [+ or -] 0.33; 1.00 (0.5-1.7) 0.015
Sol IKA 2, mm 0.79 [+ or -] 0.22; 0.80 (0.4-1.2)
Sol EKA 1, mm 0.97 [+ or -] 0.30; 1.00 (0.6-1.6) 0.035
Sol EKA 2, mm 0.78 [+ or -] 0.21; 0.70 (0.5-1.4)
Sol AKA 1, mm 1.18 [+ or -] 0.38; 1.15 (0.5-2.1) 0.061
Sol AKA 2, mm 1.03 [+ or -] 0.25; 1.00 (0.6-1.5)
Ortalama [+ or -] SS; Mediyan (En dusuk-En yuksek) degerleri
Bayanlarda eslestirilmis T testi ile baylarda Wilcoxon T testi
AD--anlamli degil, AKA--ana karotis arter, EKA--eksternal karotis
arter, IKA--internal karotis arter, IMK--intima media kalinligi,
M--mediyan degeri, ss--standart sapma
Tablo 4. Kitlede, bay ve bayanlarda IMK ortalama gerileme bulgulan
Bayanlarda
Ortalama gerileme, mm p
IMK ortalamasindaki 0.10 [+ or -] 0.19
gerileme 0.08 0.004
(-0.28-0.52)
Baylarda
Ortalama gerileme, mm p
IMK ortalamasindaki 0.18 [+ or -] 0.29
gerileme 0.14 0.007
(-0.48-0.95)
Arastirma kitlesi
Ortalama gerileme, mm p
IMK ortalamasindaki 0.13 [+ or -] 0.23
gerileme 0.10 <0.001
(-0.48-0.95)
Ortalama [+ or -] SS, Mediyan (En dusuk-En yuksek) degerleri
Bayanlarda eslestirilmis T testi ile baylarda Wilcoxon T testi
IMK--intima media kalinligi, M--mediyan degeri, ss--standart sapma
Tablo 5. Karotis arter IMK'larinda losartan sagaltimi ile olusan
gerileme yuzdeleri ve bay-bayan arasi farklilik istatistigi
Parametreler Gerileme, p *
% Bay-hayan
Sag IKA 9.39 AD
Sag EKA 2.44 AD
Sag AKA 6.06 AD
Sol IKA 12.04 AD
Sol EKA 7.43 AD
Sol AKA 7.32 AD
Ortalama kalinlikta 9.39 AD
* Mann-Whitney U testi
AD--anlamli degil, AKA--ana karotis arter, EKA--eksternal karotis
arter, IKA--internal karotis arter, IMK--intima media kalinligi
Tablo 6. Plagi olan ve olmayan gruplarda IMK ortalama gerileme
yuzdeleri icin farklilik istatistigi
Parametreler Plagi olmayanlarda gerileme, % (s=37)
Sag IKA 6.41 ; 11.11, (-100.00-42.86)
Sag EKA -4.05 ; 00.00, (-66.67-41.67)
Sag AKA 3.13 ; 00.00, (-100.00-38.46)
Sol IKA 6.78 ; 12.50, (-140.00-57.14)
Sol EKA 0.91 ; 00.00, (-50.00-50.00)
Sol AKA 4.46 ; 16.66, (-180.00-41.18)
Ortalama kalinlikta 5.12 ; 8.33, (-90.63-38.75)
Parametreler Plagi olanlarda gerileme, % (s=12) p *
Sag IKA 18.59 ; 20.83, (-20.00-80.00) AD
Sag EKA 22.45 ; 25.39, (-42.86-60.00) 0.006
Sag AKA 15.09 ; 15.00, (-22.22-62.50) AD
Sol IKA 28.28 ; 26.13, (-30.00-73.33) 0.05
Sol EKA 27.55 ; 33.33, (-25.00-60.00) 0.006
Sol AKA 16.16 ; 8.71, (-16.67-60.00) AD
Ortalama kalinlikta 22.59 ; 27.53, (-19.67-64.77) 0.006
Yuzde ve Mediyan (En dusuk-En yuksek) degerleri
*--Mann-Whitney U testi
AD--anlamli degil, AKA--ana karotis arter, EKA--eksternal karotis
arter, IKA--internal karotis arter, IMK--intima media kalinligi,
M--mediyan degeri
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