title: High plasma levels of endothelin-1 enhance the predictive value of preclinical atherosclerosis for future cerebrovascular and cardiovascular events: a 20-year prospective study.
abstract: OBJECTIVE
  Clinical and experimental evidence suggests that endothelin-1 (ET-1) plays a role in cardiac and vascular disease. In the present study, we investigated the prognostic significance of ET-1 for cerebrovascular and cardiovascular outcome, in a 20-year follow-up.
  
  
  METHODS
  We studied 82 originally healthy individuals, referred to our Unit of Cardiovascular Prevention, to evaluate the presence of asymptomatic carotid lesions. We subdivided these individuals into two groups, according to the plasma values of ET-1 (respectively ≤ or >2.7 pg/ml). Traditional cardiovascular risk factors were investigated, and by carotid ultrasound examination, we distinguished between normal individuals and those with intima-media thickening or asymptomatic carotid plaque.
  
  
  RESULTS
  Major cardiac and cerebral events (all-cause death, myocardial infarction, revascularization procedures, fatal and nonfatal stroke) were registered in 41 individuals and significantly more in those with high vs. low ET-1 levels (95 vs. 5%; P < 0.0001). Furthermore, by logistic multivariate regression analysis, we found that among all evaluated baseline clinical and laboratory variables, hypertension [odds ratio (OR): 20.4 (3.3-127), P = 0.001], high ET-1 concentrations [OR: 1.4 (1.0-1.8), P = 0.02] and the presence of intima-media thickness or asymptomatic carotid plaque [OR: 3.7 (1.14-12.1), P = 0.02] were independent predictors of future events. Finally, integrating technical and laboratory data, high levels of ET-1 have defined a high risk of major cardiac and cerebral event and stroke at follow-up, which increased in relation to the progression of carotid atherosclerosis (P < 0.05).
  
  
  CONCLUSIONS
  ET-1 plasmatic levels significantly influence the cardiovascular and cerebrovascular risk profile, beyond traditional cardiovascular risk factors and preclinical carotid atherosclerosis.
authors.affiliation: Division of Cardiology, Department of Internal Medicine and Cardiovascular Disease, Centre for the Early Diagnosis of Preclinical and Multifocal Atherosclerosis and for Secondary Prevention, University Hospital 'P. Giaccone', University of Palermo, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Novo
authors.forename: Angela
authors.initials: A
authors.lastname: Sansone
authors.forename: Manfredi
authors.initials: M
authors.lastname: Rizzo
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Guarneri
authors.forename: Claudio
authors.initials: C
authors.lastname: Pernice
authors.forename: Salvatore
authors.initials: S
authors.lastname: Novo
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D002561:Cerebrovascular Disorders / Q000175:diagnosis; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000000981:diagnostic imaging; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D019332:Endothelin-1