Subklinik Aterosklerozun Serum Endotelin-1 Düzeyi ile Değerlendirilmesi

Yıl 2021, Cilt: 47 Sayı: 1, 63 - 66, 01.04.2021

Şeyda Günay , Emre Sarandöl , Ali Aydınlar

https://doi.org/10.32708/uutfd.857404

Öz

Ateroskleroz ve ilişkili hastalıklar tüm dünyada en önde gelen ölüm nedenidir. Koroner arterlerde aterosklerotik tutulumun başlamasından daha önce endotel işlev bozukluğu ortaya çıkar. Aterosklerozu organ tutulumu ortaya çıkmadan teşhis etmek önemlidir. Bu çalışmada, subklinik aterosklerozun serum endotelin-1 (ET-1) düzeyi ile değerlendirilmesi amaçlandı. Göğüs ağrısı şikayeti ile başvuran ve koroner iskemi açısından egzersiz stres testi (EST) veya miyokard perfüyon sintigrafisi (MPS) planlanan hastalar çalışmaya alındı. Öyküsünde anjiyografik olarak kanıtlanmış koroner arter hastalığı (KAH) olan hastalar çalışmaya dahil edilmedi. İskemi testi öncesinde hastalardan serum ET-1 ölçümü için kan örneği alındı. İskemi saptananlar koroner anjiyografi (KAG) ile değerlendirilidi. KAG sonuçlarına göre hastalar, klinik olarak anlamlı KAH olanlar (grup-1) ve olmayanlar (grup-2) olarak gruplandı. İskemi saptanmayanlar ise grup-3 olarak tanımlandı. Bilinen KAH öyküsü olmayan 48 hasta (ortalama yaş:57,4±10,9 ve 23’ü (%48) kadın) çalışmaya alındı. Hastaların 13’ü (%27) diyabetik, 26’sı (%54) hipertansif ve 10’u (%20) hiperlipidemikti. 17 hastada (%35,4) EST veya MPS ile iskemi saptanmazken (grup-3), 31 hastada iskemi mevcuttu. İskemi saptanarak KAG yapılan hastaların 21’inde (%67,7) klinik olarak anlamlı KAH saptandı (grup-1), 10’unda (%32,3) klinik olarak anlamlı KAH saptanmadı (grup-2). Medyan [min-maks] serum endotelin-1 seviyesi grup-1’de 15,9 [8,8-93,4] ng/L, grup-2’de 26,9 [8,5-55,5]ng/L, grup-3’te 21,8 [8,6-97,4] ng/L saptandı. Serum ET-1 düzeyleri açısndan gruplar arasında istatiksel açıdan anlamlı farklılık saptanmadı (p=0,127). Koroner arter hastalığı şüphesi olan hastalarda serum ET-1 düzeyleri subklinik ateroskleroz için öngördürücü değildir.

Anahtar Kelimeler

iskemi, endotelin, ateroskleroz, subklinik

Evaluation of Subclinical Atherosclerosis with Serum Endothelin-1 Levels

Öz

Atherosclerosis and related diseases are the leading causes of death worldwide. Endothelial dysfunction occurs before the onset of atherosclerotic involvement in coronary arteries. It is important to diagnose atherosclerosis before organ involvement occurs. In this study, it was aimed to evaluate subclinical atherosclerosis by serum endothelin-1 (ET-1) levels in the subclinical period. Patients who presented with a complaint of chest pain and were scheduled for an exercise stress test (EST) or myocardial perfusion scintigraphy (MPS) in terms of coronary ischemia were included in the study. Patients with known angiographically proven coronary artery disease (CAD) were excluded from the study. Before the ischemia test, blood samples were taken from the patients for serum ET-1 measurement. Those with ischemia were evaluated by coronary angiography (CAG). According to the CAG results, those with clinically significant CAD (group-1) and those without clinically significant CAD (group-2) were grouped. Those without ischemia were defined as group-3. A total of 48 patients (mean age: 57.4 ± 10.9 years, and 23 (48%) females) without a known history of CAD were included in the study. 13 (27%) of the patients were diabetic, 26 (54%) of the patients were hypertensive hypertensive and 10 (20%) of the patients were hyperlipidemic. While ischemia was not detected in 17 patients (35.4%) with EST or MPS (group-3), 31 patients had ischemia and underwent CAG. Among those, clinically significant CAD was detected in 21 (67.7%) patients (group-1), and clinically significant CAD was not detected in 10 (32.3%) patients (group-2). Median [min-max] serum endothelin-1 level in group-1 was 15.9 [8.8-93.4] ng / L, in group- 2 it was 26.9 [8.5 -55.5] ng / L , and in group-3 it was 21.8[8.6-97.4] ng / L. There was no statistically significant difference between the groups in terms of serum ET-1 levels (p = 0.127). Serum ET-1 levels are not predictive of subclinical atherosclerosis in patients with suspected coronary artery disease.

Anahtar Kelimeler

ischemia, endothelin, atherosclerosis, subclinical

Kaynakça

• 1) Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801-9. doi: 10.1038/362801a0. PMID: 8479518.
• 2) Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. Erratum in: Circulation. 2012 Jun 5;125(22):e1002. PMID: 22179539; PMCID: PMC4440543.
• 3) Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37. doi: 10.1152/ajpcell.1996.271.5.C1424. PMID: 8944624.
• 4) Wagner OF, Christ G, Wojta J, Vierhapper H, Parzer S, Nowotny PJ, Schneider B, Waldhäusl W, Binder BR. Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem. 1992 Aug 15;267(23):16066-8. PMID: 1644793.
• 5) Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391-415. doi: 10.1146/annurev.physiol.61.1.391. PMID: 10099694.
• 6) Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0. PMID: 2451132.
• 7) Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013 Aug 20;128(8):873-934. doi: 10.1161/CIR.0b013e31829b5b44. Epub 2013 Jul 22. PMID: 23877260.
• 8) Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000 Mar 7;101(9):948-54. doi: 10.1161/01.cir.101.9.948. PMID: 10704159.
• 9) Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000 Apr 25;101(16):1899-906. doi: 10.1161/01.cir.101.16.1899. PMID: 10779454.
• 10) Fichtlscherer S, Breuer S, Zeiher AM. Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the "vulnerable" patient. Circulation. 2004 Oct 5;110(14):1926-32. doi: 10.1161/01.CIR.0000143378.58099.8C. Epub 2004 Sep 27. PMID: 15451794..
• 11) Mitani H, Takimoto M, Bandoh T, Kimura M. Increases of vascular endothelin-converting enzyme activity and endothelin-1 level on atherosclerotic lesions in hyperlipidemic rabbits. Eur J Pharmacol. 2000 Jan 17;387(3):313-9. doi: 10.1016/s0014-2999(99)00808-0. PMID: 10650177.
• 12) Zeiher AM, Krause T, Schächinger V, Minners J, Moser E. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation. 1995 May 1;91(9):2345-52. doi: 10.1161/01.cir.91.9.2345. PMID: 7729020..
• 13) Hasdai D, Gibbons RJ, Holmes DR Jr, Higano ST, Lerman A. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation. 1997 Nov 18;96(10):3390-5. doi: 10.1161/01.cir.96.10.3390. PMID: 9396432.
• 14) Firth JD, Ratcliffe PJ. Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. J Clin Invest. 1992 Sep;90(3):1023-31. doi: 10.1172/JCI115915. PMID: 1522210; PMCID: PMC329959.
• 15) Brunner F. Tissue endothelin-1 levels in perfused rat heart following stimulation with agonists and in ischaemia and reperfusion. J Mol Cell Cardiol. 1995 Sep;27(9):1953-63. doi: 10.1016/0022-2828(95)90017-9. PMID: 8523455..
• 16) Wang X, Douglas SA, Louden C, Vickery-Clark LM, Feuerstein GZ, Ohlstein EH. Expression of endothelin-1, endothelin-3, endothelin-converting enzyme-1, and endothelin-A and endothelin-B receptor mRNA after angioplasty-induced neointimal formation in the rat. Circ Res. 1996 Feb;78(2):322-8. doi: 10.1161/01.res.78.2.322. PMID: 8575076.
• 17) Douglas SA, Louden C, Vickery-Clark LM, Storer BL, Hart T, Feuerstein GZ, Elliott JD, Ohlstein EH. A role for endogenous endothelin-1 in neointimal formation after rat carotid artery balloon angioplasty. Protective effects of the novel nonpeptide endothelin receptor antagonist SB 209670. Circ Res. 1994 Jul;75(1):190-7. doi: 10.1161/01.res.75.1.190. PMID: 8013078..
• 18) Kaski JC, Elliott PM, Salomone O, Dickinson K, Gordon D, Hann C, Holt DW. Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J. 1995 Dec;74(6):620-4. doi: 10.1136/hrt.74.6.620. PMID: 8541166; PMCID: PMC484117..
• 19) Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC Jr. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med. 1991 Oct 3;325(14):997-1001. doi: 10.1056/NEJM199110033251404. PMID: 1886637.
• 20) Stewart DJ, Kubac G, Costello KB, Cernacek P. Increased plasma endothelin-1 in the early hours of acute myocardial infarction. J Am Coll Cardiol. 1991 Jul;18(1):38-43. doi: 10.1016/s0735-1097(10)80214-1. PMID: 2050938.
• 21) Minamino T, Kurihara H, Takahashi M, Shimada K, Maemura K, Oda H, Ishikawa T, Uchiyama T, Tanzawa K, Yazaki Y. Endothelin-converting enzyme expression in the rat vascular injury model and human coronary atherosclerosis. Circulation. 1997 Jan 7;95(1):221-30. doi: 10.1161/01.cir.95.1.221. Erratum in: Circulation 1997 Apr 1;95(7):1975. PMID: 8994440.
• 22) Rossi GP, Colonna S, Pavan E, Albertin G, Della Rocca F, Gerosa G, Casarotto D, Sartore S, Pauletto P, Pessina AC. Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. Circulation. 1999 Mar 9;99(9):1147-55. doi: 10.1161/01.cir.99.9.1147. PMID: 10069781.
• 23) Zeiher AM, Ihling C, Pistorius K, Schächinger V, Schaefer HE. Increased tissue endothelin immunoreactivity in atherosclerotic lesions associated with acute coronary syndromes. Lancet. 1994 Nov 19;344(8934):1405-6. doi: 10.1016/s0140-6736(94)90571-1. PMID: 7968078..
• 24) Boulanger CM, Tanner FC, Béa ML, Hahn AW, Werner A, Lüscher TF. Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. Circ Res. 1992 Jun;70(6):1191-7. doi: 10.1161/01.res.70.6.1191. PMID: 1315634.
• 25) Zeiher AM, Goebel H, Schächinger V, Ihling C. Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation. 1995 Feb 15;91(4):941-7. doi: 10.1161/01.cir.91.4.941. PMID: 7850978.
• 26) Omland T, Lie RT, Aakvaag A, Aarsland T, Dickstein K. Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction. Circulation. 1994 Apr;89(4):1573-9. doi: 10.1161/01.cir.89.4.1573. PMID: 8149523.
• 27) Kavousi M, Leening MJ, Nanchen D, Greenland P, Graham IM, Steyerberg EW, Ikram MA, Stricker BH, Hofman A, Franco OH. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA. 2014 Apr 9;311(14):1416-23. doi: 10.1001/jama.2014.2632. PMID: 24681960.