Endothelin-1 and nitric oxide in 3-year prognosis after acute myocardial infarction
Abstract
Background/Aim. Acute myocardial infarction (AMI) is an important cause of mortality/morbidity worldwide. Biomarkers improve diagnostic and prognostic accuracy in AMI. The aim of this study was to investigate an increase of markers of endothelial dysfunction in AMI, measured on the 3rd day after the initial event and to investigate their association with short- and long-term (3-year) prognosis (outcome). Methods. The prospective study included 108 patients with AMI in the experimental group and 50 apparently healthy subjects in the control group. Endothelin-1 (ET-1) and nitric oxide degradation products (NOx) were determined. Results. The average age of the participants in the experimental group was 62 ± 10 years and 59 ± 9 years in the control group; 74.1% of the patients in experimental group were males and 68.8% in the control group. In 74.1% of the patients, ST-elevation myocardial infarction (STEMI) was diagnosed, and 25.9% of the patients presented with non-ST-elevation myocardial infarction (NSTEMI). Thirteen (5.6%) patients died during 3 years and they had significantly higher ET-1 levels compared to survivors [4.02 (2.72–5.93) vs 3.06 (2.23–3.58) pg/mL; p = 0.015]. Endothelin-1 in 46 (42.6%) patients with composite endpoint (3-year mortality and rehospitalization) was significantly increased compared to other patients [3.14 (2.54–4.41) vs 3.05 (2.18–3.56) pg/mL; p = 0.035]. Intrahospital complications were found in 41 (48%) patients. Participants with echocardiographically detected complications (ventricular dyskinesia, left ventricular thrombus and papillary muscle rupture) had higher ET-1 levels compared to other patients [4.02 (2.78–5.57) vs 3.06 (2.29–3.66) pg/mL; p = 0.012]. Endothelin-1 concentration above the 75th percentile (> 3.77 pg/mL) was associated with the increased risk for composite endpoint [Log Rank (χ2 = 13.44; p < 0.001)]. Patients who were rehospitalized had significantly lower NOx concentration [125.5 (111.4–143.6) vs 139.3 (116.79–165.2) µmol/L; p = 0.04]. Endothelin-1 positively correlated with high sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP) and a number of leukocytes. Conclusion. Endothelin-1 and NOx were increased on the 3rd day after AMI, and they were predictors of worse short- and long-term (3-year) prognosis (outcome). Endothelin-1 positively correlated with conventional prognostic markers in AMI.
Background/Aim.
Acute myocardial infarction (AMI) is an important cause of mortality/morbidity worldwide. Biomarkers improve diagnostic and prognostic accuracy in AMI. Study aim was to investigate an increase of markers of endothelial dysfunction in AMI, measured on the 3rd day after the initial event and to investigate their association with short and long term (3-year) prognosis.
Methods.
Prospective study included 108 patients with AMI in the experimental group and 50 apparently healthy subjects in the control group. Endothelin-1 and nitric oxide degradation products (NOx) were investigated.
Results.
The average age was 62±10 years in the experimental and 59±9 in the control group, 74.1% being males in experimental and 68.8% in the control group. In 74.1% of patients, ST-elevation myocardial infarction (STEMI) was diagnosed, and 25.9% of patients presented with non-ST-elevation myocardial infarction (NSTEMI). Thirteen (5.6%) patients died during 3 years and they had significantly higher ET-1 levels compared to survivors [4.02(2.72-5.93) vs. 3.06(2.23-3.58) pg/mL, p=0.015]. Endothelin-1 in 46(42.6%) patients with composite endpoint (3-year mortality and rehospitalization) was significantly increased compared to other patients [3.14(2.54-4.41) vs. 3.05(2.18-3.56) pg/mL, p=0.035]. Intrahospital complications were found in 41(48%) patients. Participants with echocardiographycally detected complications (ventricular dyskinesia, left ventricular thrombus and papillary muscle rupture) had higher ET-1 levels compared to other patients [4.02(2.78-5.57) vs. 3.06(2.29-3.66) pg/mL, p=0.012]. Endothelin-1 concentration above the 75th percentile (>3.77 pg/mL) was associated with the increased risk for composite endpoint [Log Rank (χ2=13.44, p<0.001)]. Patients who were rehospitalized had significantly lower NOx concentration [125.5(111.4-143.6) vs. 139.3(116.79-165.2) µmol/L, p=0.04]. Endothelin-1 positively correlated with high sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP) and number of leukocytes.
Conclusion.
Endothelin-1 and NOx were increased on the 3rd day after AMI, and they were predictors of worse short and long term (3-year) prognosis. Endothelin-1 positively correlated with conventional prognostic markers in AMI.
References
WHO. Fact sheet N8310. 2011. Available from: http://www.who.int/mediacentre/factsheets/fs310/en/index.html
Heitzer T, Schlinzig T, Krohn K, Meinertz T, Münzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104(22): 2673−8.
Yao D, Vlessidis AG, Evmiridis NP, Siminelakis S, Dimitra N. Possible mechanism for nitric oxide and oxidative stress in-duced pathophysiological variance in acute myocardial infarc-tion development. A study by a flow injection chemilumines-cence method. Anal Chim Acta 2004; 505: 115−23.
Bagatini MD, Martins CC, Battisti V, Gasparetto D, Rosa CS, Spanevello RM, et al. Oxidative stress versus antioxidant defens-es in patients with acute myocardial infarction. Heart Vessels 2011; 26(1): 55−63.
Warner TD. Relationships between the endothelin and nitric oxide pathways. Clinical and Clin Exp Pharmacol Physiol 1999; 26(3): 247−52.
Bourque SL, Davidge ST, Adams MA. The interaction between endothelin-1 and nitric oxide in the vasculature: New perspec-tives. Am J Physiol Regul Integr Comp Physiol 2011; 300(6): 1288−95.
Bhandari SS, Davies JE, Struck J, Ng LL. Plasma C-terminal proEndothelin-1 (CTproET-1) is affected by age, renal func-tion, left atrial size and diastolic blood pressure in healthy sub-jects. Peptides 2014; 52: 53−7.
Gottlieb SS, Harris K, Todd J, Estis J, Christenson RH, Torres V, et al. Prognostic significance of active and modified forms of en-dothelin 1 in patients with heart failure with reduced ejection fraction. Clin Biochem 2015; 48(4−5): 292−6.
Drawnel FM, Archer CR, Roderick LH. The role of the para-crine/autocrine mediator endothelin-1 in regulation of cardiac contractility and growth. Br J Pharmacol 2013; 168(2): 296−317.
Kelly JJ, Whitworth JA. Endothelin-1 as a mediator in cardiovas-cular disease. Clin Exp Pharmacol Physiol 1999; 26(2): 158−61.
LoPresti R, Catania A, Amico TD, Montana M, Caruso M, Caimi G. Oxidative stress in young subjects with acute myocardial in-farction: Evaluation at the initial stage and after 12 months. Clin Appl Thromb Hemost 2008; 14(4): 421−7.
Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2011; 15(7): 1957−97.
Freixa X, Heras M, Ortiz JT, Argiró S, Guasch E, Doltra A, et al. Usefulness of endothelin-1 assessment in acute myocardial in-farction. Rev Esp Cardiol 2011; 64(2): 105−10.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. The Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Defi-nition of Myocardial Infarction. Third universal definition of myocardial infarction. Eur Heart J 2012; 33(20): 2551−67.
Navarro-Gonzálvez JA, García-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem 1998; 44(3): 679−81.
Chan D, Ng LL. Biomarkers in acute myocardial infarction. BMC Med 2010; 8(1): 34.
Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and oth-er emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 2006; 47(8 Suppl): C19−31.
Eggers KM, James S, Venge P, Lindahl B. Prognostic implications of changes in cardiac troponin I levels in patients with non-ST elevation acute coronary syndrome. Biomarkers 2013; 18(8): 668−72.
Giannitsis E, Steen H, Kurz K, Ivandic B, Simon AC, Futterer S, et al. Cardiac magnetic resonance imaging study for quantifica-tion of infarct size comparing directly serial versus single time-point measurements of cardiac troponin T. J Am Coll Cardiol 2008; 51(3): 307−14.
Givertz MM, Colucci W. New targets for heart-failure therapy: Endothelin, inflammatory cytokines, and oxidative stress. Lan-cet 1998; 352(Suppl 1): S134−8.
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; 18(1): 38−43.
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; 89(4): 1573−9.
Tomoda H. Plasma endothelin-1 in acute myocardial infarction with heart failure. Am Heart J 1993; 125(3): 667−72.
McCabe C, Hicks MN, Kane KA, Wainwright CL. Electrophysio-logical and haemodynamic effects of endothelin ETA and ETB receptors in normal and ischaemic working rabbit hearts. Br J Pharmacol 2005; 146(1): 118−28.
Singh AD, Amit S, Kumar OS, Rajan M, Mukesh N. Cardiopro-tective effects of bosentan, a mixed endothelin type A and B receptor antagonist, during myocardial ischaemia and reperfu-sion in rats. Basic Clin Pharmacol Toxicol 2006; 98(6): 604−10.
Bolli R. Cardioprotective function of inducible nitric oxide syn-thase and role of nitric oxide in myocardial ischemia and pre-conditioning: An overview of a decade of research. J Mol Cell Cardiol 2001; 33(11): 1897−918.
Ramzy D, Rao V, Tumiati LC, Xu N, Sheshgiri R, Miriuka S, et al. Elevated endothelin-1 levels impair nitric oxide homeostasis through a PKC-dependent pathway. Circulation 2006; 114(1 Suppl): I319−26.
Mayyas F, Al-Jarrah M, Ibrahim K, Mfady D, van Wagoner DR. The significance of circulating endothelin-1 as a predictor of coronary artery disease status and clinical outcomes following coronary artery catheterization. Cardiovasc Pathol 2015; 24(1): 19−25.
Zweier JL, Talukder M. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006; 70(2): 181−90.
Eitel I, Nowak M, Stehl C, Adams V, Fuernau G, Hildebrand L, et al. Endothelin-1 release in acute myocardial infarction as a predictor of long-term prognosis and no-reflow assessed by contrast-enhanced magnetic resonance imaging. Am Heart J 2010; 159(5): 882−90.
Adlbrecht C, Andreas M, Redwan B, Distelmaier K, Mascherbauer J, Kaider A, et al. Systemic endothelin receptor blockade in ST-segment elevation acute coronary syndrome protects the mi-crovasculature: A randomised pilot study. Eurointervention 2012; 7(12): 1386–95.
Niccoli G, Lanza GA, Shaw S, Romagnoli E, Gioia D, Burzotta F, et al. Endothelin-1 and acute myocardial infarction: A no-reflow mediator after successful percutaneous myocardial re-vascularization. Eur Heart J 2006; 27(15): 1793−8.