title: Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events.
abstract: BACKGROUND
  Hyperhomocysteinaemia is independently associated with atherosclerotic disease. Methionine loading could improve the predictive value of hyperhomocysteinaemia by detecting mild disturbances in enzyme activity. The aims of this study were to determine the beneficial effect of methionine loading on the predictive value of homocysteine testing for long-term mortality and major adverse cardiac events (MACE).
  
  
  METHODS
  In an observational study, 1122 patients with suspected or known vascular disease, underwent homocysteine testing, which was measured fasting and again 6 h after methionine loading. Hyperhomocysteinaemia was defined as a fasting level > or =15 micromol/L and post-methionine loading level > or =45 micromol/L or an increase of > or =30 micromol/L above fasting levels. Primary end-points were death and MACE. Multivariate Cox regression analysis was used, adjusting for all cardiac risk factors.
  
  
  RESULTS
  During follow up (mean 8.9 +/- 3.4 years), 98 patients died (8.7%), 86 had a MACE (7.7%), 579 patients had normal tests, 134 patients had only fasting hyperhomocysteinaemia, 226 only post-methionine hyperhomocysteinaemia and 183 patients had both. In multivariate analysis, overall survival and MACE-free survival were significantly worse for those with fasting hyperhomocysteinaemia, with hazard ratios of 1.86 (95% confidence interval (CI) 1.20-2.87) and 2.24 (95%CI 1.41-3.53), respectively. The addition of hyperhomocysteinaemia after methionine loading did not significantly increase the risk of death or MACE, with hazard ratios of 0.97 (95%CI 0.52-1.81) and 0.89 (95%CI 0.47-1.69), respectively.
  
  
  CONCLUSIONS
  The presence of post-methionine hyperhomocysteinaemia did not significantly alter risk of death or MACE in patients with normal or increased fasting homocysteine levels, respectively. In conclusion, methionine loading does not improve the predictive value of homocysteine testing with regard to long-term mortality or MACE.
authors.affiliation: Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Dunkelgrun
authors.forename: S E
authors.initials: SE
authors.lastname: Hoeks
authors.forename: O
authors.initials: O
authors.lastname: Schouten
authors.forename: H H H
authors.initials: HH
authors.lastname: Feringa
authors.forename: G M J M
authors.initials: GM
authors.lastname: Welten
authors.forename: R
authors.initials: R
authors.lastname: Vidakovic
authors.forename: Y R B M
authors.initials: YR
authors.lastname: van Gestel
authors.forename: R T
authors.initials: RT
authors.lastname: van Domburg
authors.forename: D
authors.initials: D
authors.lastname: Goei
authors.forename: R
authors.initials: R
authors.lastname: de Jonge
authors.forename: J
authors.initials: J
authors.lastname: Lindemans
authors.forename: D
authors.initials: D
authors.lastname: Poldermans
mesh_terms: D000328:Adult; D005260:Female; D006331:Heart Diseases / Q000097:blood* / Q000401:mortality; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000401:mortality; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D011237:Predictive Value of Tests
chemical_list: D006710:Homocysteine; D008715:Methionine