Reference Ranges for Homocysteine Concentrations

Summary

Reference ranges are used to interpret results, to confirm a diagnosis and to define levels at which a certain blood component may increase risk of a disease. Therefore care should be taken in defining the range in which the results of 95% of a healthy population would be expected to fall. Subjects should constitute a random sample of the healthy population and the procedure should be standardized to exclude pre-analytical factors that may impact on the assay result. When the distribution of the data is parametric, the central 95% interval may be calculated as mean ± 2 standard deviations of the mean, and if the data distribution is non-parametric, as is the case with plasma total homocysteine, the central 95% interval is obtained by computing the 2.5^th and the 97.5^th percentiles. It may however be inappropriate to generate reference data from populations who have a high incidence of CHD and who may have sub-clinical disease. Furthermore, the validity of the plasma homocysteine reference range may be affected by certain confounding variables, e.g. use of different analytical methods and standards, gender, age, vitamin nutritional status, and race. In this chapter the plasma homocysteine reference range is redefined by taking vitamin nutritional status into consideration. Different models indicate that the upper limit of normal for the plasma homocysteine concentration is 12 µmol/L. The clinical relevance of this cutoff value is tested by evaluating the outcome of studies that applied similar cutoff values in assessing CHD risk. Standardization of the analytical method is required before a reference range for plasma tHcy can be applied universally.