Resuscitation 53 (2002) 71–76

Plasma endothelin in patients with acute aortic disease

Andreas Wagner a, Hans Domanovits a, Michael Holzer a, Julia Kofler a,Martin Roggla a, Markus Mullner a, Elisabeth Oschatz a, Manfred Prager b,

Michael Grimm c, Fritz Sterz a,*, Anton N. Laggner a

a Department of Emergency Medicine, Uni�ersity of Vienna, Vienna General Hospital, Vienna, Austriab Department of General Surgery, Uni�ersity of Vienna, Vienna General Hospital, Vienna, Austriac Department of Thoracic Surgery, Uni�ersity of Vienna, Vienna General Hospital, Vienna, Austria

Received 8 July 2001; received in revised form 6 September 2001; accepted 5 December 2001

Abstract

Purpose and background: We investigated the plasma levels of endothelin 1/2 in patients with acute symptoms relating to aknown or newly diagnosed aortic aneurysm in order to investigate the possible role of peptides in the development of the disease.Methods: Endothelin 1/2 plasma levels were determined in patients admitted to the emergency unit with suspected acute aorticdisease. The history, type of aneurysm, outcome and laboratory findings were determined and compared to endothelin 1/2 levelscollected on admission. Results: In patients with ruptured aneurysm (n=27) or acute aortic dissection (n=18) the endothelin 1/2median levels were higher 1.1 (25th and 75th quartile 0.7, 1.7) fmol/ml than in patients (n=20) with pre-existing aneurysm 0.7(0.4, 1.1) fmol/ml (P=0.013). Patients who died had significantly higher endothelin levels 1.3 (0.8, 1.9) fmol/ml than the survivors0.8 (0.5, 1.4) fmol/ml (P=0.04). In a logistic regression analysis, only a higher blood pressure on admission was an independentpredictor of survival. Conclusion: Endothelin 1/2 levels are elevated in patients with acute dissection or ruptured aneurysm, butthey are not an independent predictor of survival. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Aorta; Blood pressure; Endothelin-1; Haemorrhage; Outcome

www.elsevier.com/locate/resuscitation

1. Introduction

Rupture is the most common cause of death inpatients with thoracoabdominal aortic aneurysm withrates ranging from 42 to 70% [1,2]. The majority ofearly deaths from all types of aortic dissection are dueto rupture of the aorta into the pleural, pericardial orabdominal cavity [3]. Surgery is recommended inknown aneurysms and/or dissection according to clini-cal judgements depending on type, localisation anddiameter [3]. However the pathophysiology of ruptureand acute dissection is poorly understood. As the num-ber of diagnosed aneurysms [4] is rising, efforts tounderstand the pathophysiology and the course of thedisease are essential to improve management.

Factors contributing to the development of aorticaneurysm are congenital (Marfan’s syndrome, Ehlers-Danlos syndrome), degenerative (cystic medial degener-ation, atherosclerotic), traumatic or mechanical(postatherotomy). Hypertension is known as the mostimportant risk factor for thoracic aortic dissection [5].Recent investigation of pathophysiology has empha-sised the possible inflammatory nature of the disease[6].

Endothelin is a 21-amino acid peptide with threeisotypes (ET-1, ET-2, ET-3). Two different receptorsubtypes for endothelin (ETA, ETB) are located in thevascular bed which mediate the vasoconstricting andvasodilatatory action of endothelin in large arteries [7].Endothelin is a possible contributor to essential hyper-tension [8]. It is also a mediator in inflammatory pro-cesses [9], its production by isolated cells is stimulatedby shear stress [10] and recently an increased expressionof endothelin receptors was identified in aortas of ratsof the Brown-Norway strain, which are known to de-

* Corresponding author. Present address: Universitatsklinik furNotfallmedizin, Wahringergurtel 18-20/6/D, 1090 Vienna, Austria.Tel.: +43-1-40400-1964; fax: +43-1-40400-1965.

E-mail address: fritz.sterz@akh-wien.ac.at (F. Sterz).

0300-9572/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved.PII: S0 3 0 0 -9572 (01 )00502 -0

A. Wagner et al. / Resuscitation 53 (2002) 71–7672

velop spontaneous aortic lesions [11]. Plasma endothe-lin has been shown to be increased in patients withsubarachnoidal haemorrhage due to ruptured intracra-nial aneurysm [12].

The aim of our study was to measure endothelin 1/2plasma levels in order to identify a possible relationbetween peptide levels and the clinical course in pa-tients with aortic disease, and to investigate if endothe-lin 1/2 plasma levels on admission could serve as aprognostic indicator.

2. Material and methods

2.1. Patients and protocol

We included all consecutive patients from June 1997to May 1999 who were admitted to the emergencydepartment of a university teaching hospital with acutesymptoms (sudden severe thoracic or abdominal pain)and a newly diagnosed or pre-existing aortic aneurysm.All patients gave written informed consent either beforeinclusion or after regaining consciousness. The protocoland the study was approved by the Institutional ReviewBoard.

Patients with acute and chronic aortic disease andsurvivors and non-survivors were compared. Furthersubgroup analysis on the characteristics of the aneu-rysm and patients were performed. The aneurysms(ruptured and dissected) were divided according to thestyle of the Stanford classification [13] according to thelocation of the pathology in aneurysms of the ascendingthoracic aorta, the descending thoracic aorta, or theabdominal aorta. The patients were subdivided accord-ing to the extent of propagation of the disease (rupture,covered rupture, acute dissection, chronic dissectionand ectasia). Rupture was defined by direct visualisa-tion of the discontinuity of the aortic wall by computedtomography, sonography, intraoperative findings or atautopsy with detection of blood in the pleural, pericar-dial or abdominal cavity. Covert rupture was defined asan intramural haematoma without detection of freeblood in the body cavities. Acute dissection was definedwhen blood separating the layers of the aortic mediawas newly diagnosed. Chronic dissection was defined asthe absence of any visible propagation of a knowndissection compared to pre-existing examinations.Ectatic aneurysm was defined as a permanent localiseddilatation of the aorta with a diameter of at least 50%greater than normal [14]. Documentation of the surgi-cal interventions and autopsy reports was used to verifythe diagnosis.

In all patients we documented the history, age of thepatients, duration of pain, blood pressure at admissionand laboratory parameters (haematocrit, creatinine)and endothelin 1/2 plasma levels immediately after

admission to our emergency department. The patientswere followed until hospital discharge and the outcome(survived/died) was recorded.

2.2. Analytical procedures

Blood samples for endothelin 1/2 were collected intoice-chilled 10-ml EDTA coated polystyrene tubes(Vacutainer, Becton Dickinson, France) on admission.Each sample was separated within 10 min by centrifu-gation at 5000 rpm at 4 °C and then stored at −70 °C.Endothelin 1/2 finally was extracted from plasma sam-ples by HPLC with Sep-Pak C18 cartridges (Waters,Millipore, Milford, MA) using methanol/water as themobile phase. The peptide was eluted with methanol/water in the volume ratio of 90:10. Dry extracts wereobtained by vacuum concentration (Speed-Vac, Savant-Instruments Farmingdale, NY). Endothelin 1/2 contentof plasma extracts, which had been reconstituted inbuffer, was determined by nonequilibrium radio im-munoadsorbent assay (RIA) with delayed addition oftracer and second antibody separation of peptidebound to anti-endothelin 1/2 (Endothelin-RIA system,Biomedica, Vienna, Austria). Details of this procedurehave been published elsewhere [15]. Because of co-ex-traction of all three isoforms of endothelin and cross-reactivity of the endothelin-antibody, our RIA couldnot discriminate between endothelin-1 and endothelin-2. Cross-reactivity of the antibody with endothelin-3however was negligible. Characteristic data of the RIAwere: recovery of synthetic endothelin from EDTAplasma: (71–83%), limit of detection (0.1 fmol/ml),linear range of calibration curve: 0.7 fmol/ml and 8.4fmol/ml, within-run precision was 10%, between-runprecision was 15%. With this method the median en-dothelin 1/2 plasma level for healthy controls was 0.6(25th and 75th quartile 0.4, 0.8) fmol/ml (n=21).

2.3. Statistical analysis

Continuous data are presented as median (25th and75th quartile) unless otherwise indicated. For the com-parison of continuous data, the Kruskal–Wallis testwith Dunn’s test for post-hoc comparison and aMann–Whitney rank sum test was used. For nominaldata Chi-square analysis of contingency tables withsubdividing the tables for post-hoc comparison withBonferroni correction was used. Spearman rank corre-lation was used to assess the association between con-tinuous variables. A logistic regression analysisaccounting for endothelin 1/2 plasma levels, age, sys-tolic blood pressure, haematocrit, creatinine, type ofaneurysm and the five predefined clinical subgroupsreferring to propagation of the disease was performedto identify independent predictors of survival. A P-value�0.05 was considered statistically significant.

A. Wagner et al. / Resuscitation 53 (2002) 71–76 73

Table 1Demographic data, laboratory results and endothelin 1/2 levels ac-cording to acuteness of the aneurysm

Chronic P-valueAcute

45n 2070 (65, 75)69 (55, 74) 0.38Age0.7 (0.4, 1.1)ET (fmol/ml) 0.011.1 (0.7, 1.7)150 (120, 160)140 (110, 160) 0.98SAP (mmHg)

Creat 1.37 (0.99, 1.84) 1.18 (0.96, 1.73) 0.57(mg/100 ml)

35 (32, 40)Hct (%) 0.4236 (28, 38)6 (30%)Hypertension 0.1120 (44%)4 (20%)1 (2%)Renal disease

32 (71%)Survivors 19 (95%) 0.0470.0135/3/7 3/5/12Surgery

(yes/after 24h/no)

ET, endothelin 1/2 plasma levels; SAP, systolic arterial pressure;Creat, serum creatinine; Hct, haematocrit; AAA, aneurysm of theabdominal aorta; TAAA, aneurysm of the ascending thoracic aorta;TAAB, aneurysm of the descending thoracic aorta; data are presentedas median (25th and 75th quartile).

(one patient), diverticulitis (one patient) and sick sinussyndrome (one patient) were deemed as the reason forthe patient’s discomfort.

Thirteen patients with acute aortic disease died, fivedied in the preoperative period, and eight postopera-tively after a median of 7 days (range 1–14). In thegroup without acute aortic disease one patient died ofmyocardial infarction 21 days after admission (Table1).

Fourteen patients died during the hospital stay. Inthese patients endothelin 1/2 plasma levels were signifi-cantly higher than in survivors. The patients who diedhad lower blood pressure, higher age, lower haemat-ocrit, higher creatinine and the type of aneurysm dif-fered from survivors (Table 2).

In a logistic regression analysis which included en-dothelin 1/2 plasma levels, age, systolic blood pressure,haematocrit, creatinine, type of aneurysm and the fivepredefined subgroups referring to progress of the dis-ease, only systolic blood pressure proved to be anindependent predictor of survival (odds ratio 1.031,95% confidence interval 1.001–1.062, P=0.044).

Subgroup analysis of the patients according to theprogress of the disease process (rupture, covered rup-ture, acute dissection, chronic dissection and ectasia)are presented in Table 3. The results of subgroupanalysis according to the localisation of the aneurysmare listed in Table 4.

Median plasma endothelin 1/2 level of all patientsadmitted to our department with aortic disease was 1.0(0.6, 1.6) fmol/ml, significantly higher than in normalcontrols (0.06 (0.4, 0.8)) (P=0.002).

There was no significant difference between endothe-lin 1/2 levels in patients with rupture (n=27) with alevel of 1.3 (0.8, 1.7) fmol/ml compared to acute dissec-tion (n=18) with a level of 0.8 (0.6, 1.6) fmol/ml(P=0.26). But there was a difference regarding medianage 72 (range 51–84) versus 57 (33–77) (P�0.01),

3. Results

During the study period we included 65 patients, 45(69%) were male. The median age was 69 years (range33–85). Abdominal aneurysms were found in 30 pa-tients, an aneurysm originating in the ascending tho-racic aorta in 20 patients, and an aneurysm originatingin the descending thoracic aorta in 15 patients. A freeor covered rupture was diagnosed in 27 patients (42%),an acute dissection in 18 patients (28%). An aorticaneurysm without signs of acute dissection or rupturewas diagnosed in 20 patients (30%). In these 20 patientsaneurysm tension pain (four patients), pleurisy or pneu-monia (four patients), angina pectoris (three patients),pain originating from the spine (three patients) gastritis(two patients), nephrolithias (one patient), pericarditis

Table 2Endothelin 1/2 levels, demographic data, laboratory results, localisation of the aneurysm and propagation of the disease in survivors andnon-survivors

Non-survivorsSurvivors P-value

1451n0.8 (0.5, 1.4)ET (fmol/ml) 1.3 (0.8, 1.9) 0.04

Age 74 (69, 79)69 ( 56, 74) 0.03140 (120, 160)SAP (mmHg) 110 (85, 130) �0.011.22 (0.97, 1.71)Creat (mg/100 ml) 1.82 (1.23, 2.71) 0.0336 (32, 39)Hct (%) 29 (26, 36) 0.0420/17/14 10/3/1AAA/TAAA/TAAB 0.0432/19 13/1Acute/chronic aortic disease 0.05

Rupture/dissection in patients with acute aortic disease n=45 16/16 11/2 0.02Surgery (yes/after 24 h/no) 27/8/16 11/0/3 0.15

ET, endothelin 1/2 plasma levels; SAP, systolic arterial pressure; Creat, serum creatinine; Hct, haematocrit; AAA, aneurysm of the abdominalaorta; TAAA, aneurysm of the ascending thoracic aorta; TAAB, aneurysm of the descending thoracic aorta; data are presented as median (25thand 75th quartile).

A. Wagner et al. / Resuscitation 53 (2002) 71–7674

Table 3Demographic data, laboratory results and endothelin 1/2 levels of the five patients subgroups formed according to the propagation of the disease

Covered rupture Acute dissection Chronic dissectionRupture Ectasia P-value

n 522 18 7 1367 (53, 77) 57 (48, 72) 68 (61, 75)73 (69, 77) 71 ( 66, 76)Age 0.01

1.3 (0.8, 1.7)ET (fmol/ml) 1.0 (0.6, 2.0) 0.8 (0.6, 1.6) 0.7 (0.3, 1.0) 0.8 (0.4, 1.3) 0.09100 (100, 170) 163 (143, 180) 140 (100, 140) 145 (125, 160)SAP (mmHg) �0.01125 (98, 153)1.85 (1.30, 2.71) 1.09 (0.84, 1.49) 1.30 (1.06, 1.70)1.58 (1.26, 2.13) 1.15 (0.95, 1.96)Creat (mg/100 ml) 0.0736 (26, 41) 36 (30, 38) 35 (28, 36)Hct (%) 37 (33, 42)32 (27, 38) 0.363 1 216 8AAA �0.01

4TAAA 1 12 1 2 �0.011 5 42 3TAAB 0.123

9Hypertension 3 8 3 3 0.52–Renal disease – – 1 3 0.52

4 (80%) 16 (89%) 6 (86%)12 (55%) 13 (100%)Survivors 0.024/1/0 11/2/5 1/0/6Surgery (yes/after 24 h/no) 2/5/620/0/2 �0.01

ET, endothelin 1/2 plasma levels; SAP, systolic arterial pressure; Creat, serum creatinine; Hct, haematocrit; AAA, aneurysm of the abdominalaorta; TAAA, aneurysm of the ascending thoracic aorta; TAAB, aneurysm of the descending thoracic aorta; data are presented as median (25thand 75th quartile).

systolic blood pressure 120 (100, 150) versus 163 (143,180) mmHg (P�0.01), creatinine 1.60 (1.27, 2.07) ver-sus 1.09 (0.84, 1.49) mg/dl (P�0.01). Eleven patientswith acute rupture and two patients with acute dissec-tion died (P=0.05). In four patients without acutedissection we found elevated endothelin 1/2 levels (1.4,1.6, 1.6, 2.7 fmol/ml). These patients also had chronicrenal failure.

Neither systolic blood pressure (R2=0.01, P=0.44)nor diastolic blood pressure (R2�0.01, P=0.76) onadmission were related to endothelin 1/2 concentra-tions. Age (R2�0.01, P=0.45), and the time-intervalfrom onset of pain to admission did not correlate witha higher endothelin 1/2 level (R2�0.01, P=0.85). Wefound a significant but weak correlation between en-dothelin 1/2 levels and creatinine levels (R2=0.10,P=0.01).

4. Discussion

The median plasma endothelin 1/2 level in all pa-tients admitted to our department with aortic diseasewas significantly higher than in normal controls. Inpatients with acute aortic disease, i.e. ruptured aneu-rysms and acutely dissecting aneurysms these levelswere significantly higher than in patients with pre-exist-ing dissections or aneurysms. The elevation of endothe-lin 1/2 levels in patients with aortic disease wasexpected as endothelin is known to work as a mediatorof inflammatory diseases of vessels [9] and higher en-dothelin levels are associated with hypertension [7];both are accepted risk factors for the development ofaortic disease.

However these risk factors are associated with bothacute and pre-existing aortic disease and can therefore

explain the higher endothelin 1/2 values in comparisonto the controls but not the observed significant differ-ence between acute and chronic aortic aneurysms.

As production of endothelin from endothelial cellsneeds several hours in vitro after stimulation by cate-cholamines, hypoxia [16] or sheer stress [10] overpro-duction of endothelin may precede aortic rupture. Thedynamic progression from dissection to definitive rup-ture possibly could be mediated by an endothelin ki-netic. This is supported by recent findings of increasedendothelin secretion at the sites of spontaneous tears ofthe internal elastic lamina in the distal aorta of nor-motensive Brown-Norway rats. These sites are knownto be associated with the formation of aneurysmallesions [11]. The increased endothelin secretion, whichis represented by an increase of anti-endothelin stainedendothelium overlying the elastic intima at the edges ofthe tears supports the importance of endothelin in thedevelopment of aortic aneurysm. Since endothelinseems to be a locally acting paracrine or autocrineprotein rather than a circulating hormone [17] plasmaconcentrations of endothelin are likely to represent aspillover from much higher concentrations at the inter-face between the endothelium and the vascular smoothmuscle cells. Serial determination of endothelin in pa-tients with a known aneurysm might help to clarify ifan increase of endothelin is a pathophysiologic mecha-nism in the development of rupture and consequentlycould serve as a marker in prognosticating the immi-nent rupture.

On the other hand, the elevation of endothelin 1/2 inpatients with acute aortic disease might only be aconsequence or accompanying phenomena of aorticrupture or dissection and the circulatory disturbances,as the cold pressor test and orthostasis have beenreported to stimulate endothelin production within

A. Wagner et al. / Resuscitation 53 (2002) 71–76 75

Table 4Demographic data, laboratory results and endothelin 1/2 levels according to the localisation of the aneurysm

TAAA TAAB P-valueAAA

n 30 20 1565 (48, 75) 66 (58, 69)72 (69, 75) 0.04Age

1.0 (0.5, 1.6)ET (fmol/ml) 0. 9 (0.6, 1.7) 1.0 (0.7, 1.4) 0.95155 (138, 161) 160 (135, 180)SAP (mmHg) �0.01120 (100, 143)1.17 (0.95, 1.73) 1.04 (0.85, 1.59)1.56 (1.20, 1.95) 0.03Creat (mg/100 ml)37 (33, 40) 35 (31, 38)Hct (%) 0.0732 (26, 38)11 69 0.58Hypertension

Renal disease –3 117 (85%) 14 (93%)20 (67%) 0.09Survivors

Surgery (yes/after 24 h/no) 14/0/622/5/3 2/3/10 �0.01

ET, endothelin 1/2 plasma levels; SAP, systolic arterial pressure; Creat, serum creatinine; Hct, haematocrit; AAA, aneurysm of the abdominalaorta; TAAA, aneurysm of the ascending thoracic aorta; TAAB, aneurysm of the descending thoracic aorta; data are presented as median (25thand 75th quartile).

minutes [18]. The elevation of endothelin 1/2 mightreflect a kind of repair mechanism similar to the find-ings after aneurysmal subarachnoidal haemorrhage[19].

Since renal function may influence endothelin plasmalevels it could be argued that coexisting renal diseasemight have influenced our findings. Four of the patientswithout acute dissection had elevated endothelin 1/2levels. These patients all had chronic renal failure whichis known to be associated with higher endothelin 1/2levels [20]. As no patient in the group with acuterupture or dissection had a history of pre-existing renalimpairment the influence of pre-existing impaired renalfunction on the elevated endothelin plasma levels in theacute group could be ruled out in our patients.

A history of hypertension could help to explain thedifferences in endothelin 1/2 levels compared to thenormal controls, but between the different groups withaortic disease there was no significant difference in thedistribution of hypertension in the medical history.

Although endothelin 1/2 levels were significantlyhigher in the non-surviving patients, logistic regressionanalysis showed that endothelin 1/2 levels could notindependently predict survival. This was only possiblefor a higher blood pressure on admission.

Some limitations of our study have to be mentioned.Although it might have been interesting to determinewhether elevated levels further increased or remained atthe previous level we decided to take only one bloodsample from each patient immediately after admissionin order to exclude influences of ongoing diagnostic andtherapeutic interventions (like central venous access,arterial line, transesophageal echocardiography) on theendothelin 1/2 levels. Therefore we were not able todiscriminate at what stage in the progression of thedisease the increase of endothelin started in the patientswith acute aortic disease. This should be investigated infurther studies with serial endothelin plasma level anal-ysis in patients with a pre-existing aneurysm.

The elevation of endothelin 1/2 in patients withaortic disease may have clinical importance since en-dothelin receptor antagonists like bosentan have beenintroduced in the treatment of hypertension [21]. Thesesubstances may play a role in treatment of hypertensionin patients with aortic aneurysm.

We conclude that endothelin 1/2 levels are elevated inpatients with acute dissection or ruptured aneurysm,but are not an independent predictor of survival.

Acknowledgements

We would like to thank Professor G. Geyer andthe Ludwig Boltzmann Institute for Endocrinology forsupporting the analysis of endothelin. This work wassupported by a grant from the Forschungsfoerderungs-fonds des Buergermeisters der Stadt Wien. MichaelHolzer was supported by BIOMED2 European Com-mission, DG XII for Science Research and Develop-ment, Directorate Life Science and Technologies,Biomedical and Health Research Division.

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Portuguese Abstract and Keywords

Objecti�o e contexto: Investigamos os nıveis plasmaticos de endotelina 12 em doentes com sintomas agudos relacionados com um

aneurisma da aorta conhecido ou diagnosticado de novo de forma a investigar o papel possıvel de peptıdeos no desenvolvimentoda doenca. Metodos: Determinaram-se os nıveis plasmaticos de endotelina 1

2 nos doentes admitidos na unidade de emergencia comsuspeita de doenca aortica aguda. Registou-se o tipo de aneurisma, a historia, a evolucao e os valores laboratoriais que seconfrontaram com os nıveis de endotelina 1

2 colhidos na admissao. Resultados: Em doentes com ruptura de aneurisma (n=27) oudisseccao aguda da aorta (n=18), os nıveis medios de endotelina 1

2 eram 1.1 (25° e 75° quartil, 0.7, 1.7) fmol/ml mais elevadosque em doentes (n=20) com aneurisma pre-existente 0.7 (0.4, 1.1) fmol/ml (P=0.013). Os doentes que faleceram tinham nıveissignificativamente mais elevados de endotelina 1.3 (0.8, 1.9) fmol/ml que os sobreviventes 0.8 (0.5, 1.4) fmol/ml (P=0.04). Numaanalise de regressao logıstica so a pressao arterial mais elevada na admissao era um factor predictivo independente de maiorsobrevida. Conclusao: Os nıveis de endotelina 1

2 estao elevados em doentes com disseccao aguda ou ruptura de aneurisma, mas naosao factores independentes de previsao de sobrevida. © 2002 Published by Elsevier Science Ireland Ltd

Pala�ras cha�e : Aorta; Pressao arterial; Endotelina-1; Hemorragia; Evolucao

Spanish Abstract and Keywords

Proposito y antecedentes : Investigamos el nivel plasmatico de endotelina 12 en pacientes con sıntomas agudos relacionados con un

diagnostico de aneurisma aortico, conocido o reciente, para investigar el posible rol de estos peptidos en el desarrollo de laenfermedad. Metodos : Se determinaron los niveles plasmaticos de endotelina 1

2 en pacientes admitidos en la unidad de emergenciascon sospecha de enfermedad aguda aortica. Se determinaron datos de historia clınica, tipo de aneurisma, resultado final yhallazgos de laboratorio y se compararon con niveles de endotelina 1

2 tomados al momento de admision. Resultados: En pacientescon aneurismas rotos (n=27) o diseccion aortica aguda (n=18) los niveles de endotelina 1/2 fueron 1.1 fmol/ml (cuartil 25 y 750.7, 1.7) mas altos que en pacientes con aneurisma preexistente (n=20) con 0.7 fmol/ml (0.4, 1.1), (P=0.013). Los pacientes quefallecieron presentaron niveles de endotelina de 1.3 fmol/ml (0.8, 1.9), significativamente mas altos que los sobrevivientes con 0.8fmol/ml (0.5, 1.4), (P=0.04). En un analisis de regresion logıstica, solo una presion arterial mas alta al momento de admision fueun predictor de sobrevida independiente. Conclusion : El nivel plasmatico de endotelina 1

2 esta elevado en pacientes con diseccionaguda o ruptura de aneurisma, pero no es predictor de sobrevida independiente.

Palabras cla�e : Aorta; presion arterial; Endotelina-1; Hemorragia; Resultado