A 2-step strategy to reduce the need for methionine-loading tests to diagnose hyperhomocysteinemia

• Published in: The Journal of laboratory and clinical medicine Vol. 142; no. 2; pp. 121 - 127
• Main Authors: van de Laak, Marielle F, Grobbee, Diederick E, van der Griend, Rene, de Valk, Harold W, Algra, Ale, Banga, Jan-Dirk, van der Graaf, Yolanda
• Format: Journal Article
• Language: English
• Published: Saint Louis, MO Mosby, Inc 01.08.2003; Elsevier
• Subjects: Adult; Biological and medical sciences; Fasting; Female; Homocysteine - blood; Humans; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - diagnosis; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Metabolic diseases; Methionine; Middle Aged; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; CS; MLT; CI; MTHFR; SMART; HPLC; tHcy; Choleretic; Human; Methionine; Metabolic diseases; Cardiovascular disease; Loading test; Sulfur containing aminoacid; Vascular disease; Aminoacid; Antiseptic; Clinical biology; Atherosclerosis; Risk factor; Hyperhomocysteinemia; Diagnosis; Technique; Antidote; Aminoacid disorder
• ISSN: 0022-2143; 1532-6543
• DOI: 10.1016/S0022-2143(03)00103-3

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 μmol/L or greater in women and 18.8 μmol/L or greater in men or an increase in plasma homocysteine level after methionine loading of more than 42.3 μmol/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 μmol/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.