title: A 2-step strategy to reduce the need for methionine-loading tests to diagnose hyperhomocysteinemia.
abstract: An increased plasma homocysteine level may increase the risk of cardiovascular disease. The methionine-loading test is commonly used to detect additional subjects with hyperhomocysteinemia who have normal fasting levels of homocysteine but increased post-methionine-load levels. We developed a 2-step strategy to restrict the methionine-loading test to those subjects with intermediate fasting homocysteine levels to confirm the presence of hyperhomocysteinemia. Hyperhomocysteinemia was defined as a fasting plasma homocysteine level of 16.3 micro mol/L or greater in women and 18.8 micro mol/L or greater in men or an increase in plasma homocysteine level after methionine loading of more than 42.3 micro mol/L for both sexes. From the results in 201 patients, 50 years and younger, with manifest atherosclerosis who underwent a methionine-loading test, we derived cutoff points to define an intermediate group of patients who required a methionine-loading test for hyperhomocysteinemia to be ruled out. These cutoff points were validated in a different population of 275 cardiovascular patients of similar age. The prevalence of hyperhomocysteinemia was 30% in the derivation population and 24% in the validation population. To achieve a sensitivity of 90% in diagnosing hyperhomocysteinemia, we set cutoff points of 11.3 and 9.4 micro mol/L for men and women, respectively. When these cutoff points are applied, it is possible to avoid performing the methionine-loading test in 50% to 75% of subjects tested. With a 2-step strategy to diagnose hyperhomocysteinemia, a sensitivity of 90% for the diagnosis of hyperhomocysteinemia can be achieved, and the need for the methionine-loading test is reduced substantially, with 50% to 75% of subjects no longer needing it.
authors.affiliation: Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, The Netherland.
authors.forename: Marielle F
authors.initials: MF
authors.lastname: van de Laak
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Rene
authors.initials: R
authors.lastname: van der Griend
authors.forename: Harold W
authors.initials: HW
authors.lastname: de Valk
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: Jan-Dirk
authors.initials: JD
authors.lastname: Banga
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
mesh_terms: D000328:Adult; D005215:Fasting; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008715:Methionine; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D006710:Homocysteine; D008715:Methionine