title: Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.
abstract: OBJECTIVE
  To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease.
  
  
  METHODS
  Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease.
  
  
  METHODS
  Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed.
  
  
  RESULTS
  The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥ 3/6).
  
  
  CONCLUSIONS
  The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Box 57, 00014 Helsinki, Finland; Minerva Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, 00290 Helsinki, Finland. Electronic address: anders.eriksson@helsinki.fi.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Eriksson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, S-750 07 Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Häggström
authors.affiliation: The Royal Veterinary and Agricultural University, Copenhagen, Denmark.
authors.forename: Henrik Duelund
authors.initials: HD
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, S-750 07 Uppsala, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hansson
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Box 57, 00014 Helsinki, Finland.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Järvinen
authors.affiliation: Faculty of Medicine, Hjelt Institute, University of Helsinki, Box 40, 00014, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Haukka
authors.affiliation: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, S-750 07 Uppsala, Sweden.
authors.forename: Clarence
authors.initials: C
authors.lastname: Kvart
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001947:Breeding; D004283:Dog Diseases / Q000097:blood* / Q000209:etiology; D004285:Dogs; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000097:blood / Q000150:complications / Q000662:veterinary*; D006333:Heart Failure / Q000097:blood / Q000209:etiology / Q000662:veterinary*; D008137:Longitudinal Studies; D008297:Male; D008944:Mitral Valve Insufficiency / Q000097:blood / Q000150:complications / Q000662:veterinary; D008945:Mitral Valve Prolapse / Q000097:blood / Q000150:complications / Q000662:veterinary*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor
keywords: Chronic valvular disease; Dog; Endothelial dysfunction; Natriuretic peptide