title: Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: a longitudinal observational study in the Vara-Skövde Cohort.
abstract: BACKGROUND
  The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden.
  
  
  METHODS
  In 2002-2005, 2816 adult participants (30-74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time.
  
  
  RESULTS
  We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1-2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8-1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1-1.2, p = 0.024).
  
  
  CONCLUSIONS
  Circulating endothelin-1 levels may predict CHD in women.
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 454, S-405 30, Gothenburg, Sweden. bledar.daka@allmed.gu.se.
authors.forename: Bledar
authors.initials: B
authors.lastname: Daka
authors.affiliation: Department of Molecular and Clinical Medicine, The Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Josefin.Olausson@wlab.gu.se.
authors.forename: Josefin
authors.initials: J
authors.lastname: Olausson
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 454, S-405 30, Gothenburg, Sweden. charlotte_a.larsson@med.lu.se.|Department of Clinical Sciences, Social Medicine and Global Health, Lund University, Malmö, Sweden. charlotte_a.larsson@med.lu.se.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Larsson
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 454, S-405 30, Gothenburg, Sweden. margareta.leonardsson-hellgren@vgregion.se.
authors.forename: Margareta I
authors.initials: MI
authors.lastname: Hellgren
authors.affiliation: Department of Clinical Sciences, Family Medicine, Lund University, Malmö, Sweden. lennart.rastam@med.lu.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Råstam
authors.affiliation: Department of Molecular and Clinical Medicine, The Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. per-anders.jansson@medic.gu.se.
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 454, S-405 30, Gothenburg, Sweden. ulf.lindblad@gu.se.
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindblad
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019332:Endothelin-1