title: Occurrence of hyperhomocysteinaemia in cardiovascular, haematology and nephrology patients: contribution of folate deficiency.
abstract: We investigated the contribution of plasma folate deficiency to hyperhomocysteinaemia in selected patient groups. Based on our observations, we have determined a lower folate reference interval cut-off using homocysteine as a metabolic marker of folate deficiency. Four hundred and twenty-five consecutive plasma specimens from cardiology (n = 120), haematology (n = 190) and nephrology (n = 115) patients were analysed for homocysteine and plasma folate concentrations. Healthy volunteers were used as controls (n = 117). We observed elevated homocysteine values above our upper reference limit of 13 micromol/L in 20.1%, 28.4% and 74.8% of the cardiology, haematology and nephrology patients, respectively. All but 1.9% of the patients had plasma folate values greater than the lower reference interval limit (3.4 nmol/L) for our folate assay. The percentage of patients from cardiology and haematology clinics who were hyperhomocysteinaemic and had folate values > 15 nmol/L was 5.0% and 4.2%, respectively. In contrast, 58% of our nephrology patients with folate values > 15 nmol/L were hyperhomocysteinaemic. In all three groups, an inverse relationship was found between folate and homocysteine. The folate/homocysteine ratios in the patient groups were approximately one-third of the values observed in our control group. Folate deficiency appears to be the primary cause of hyperhomocysteinaemia in our cardiology and thrombosis patients. However, severe folate deficiency appears to be uncommon. The majority of our nephrology patients are hyperhomocysteinaemic without an apparent folate deficiency. We conclude that raising the lower reference interval cut-off for folate to 15 nmol/L would help to identify individuals at risk for hyperhomocysteinaemia in our non-uraemic patient population. Increasing folate supplementation to maintain a plasma concentration above 15 nmol/L in cardiac, thrombosis and renal patients would greatly reduce the occurrence of hyperhomocysteinaemia in these patients.
authors.affiliation: Department of Pathology and Laboratory Medicine, Ottawa Hospital, ON, Canada. jdonnelly@civich.ottawa.on.ca
authors.forename: J G
authors.initials: JG
authors.lastname: Donnelly
authors.forename: P A
authors.initials: PA
authors.lastname: Isotalo
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications; D005494:Folic Acid Deficiency / Q000097:blood* / Q000235:genetics; D006402:Hematologic Diseases / Q000097:blood* / Q000150:complications; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)