Population reference ranges and determinants of plasma homocysteine levels

BACKGROUND: There is a well-known relationship between plasma homocysteine levels and the risk of cardiovascular events. Determination of homocysteine levels may also be of potential diagnostic aid in several clinical situations. The construction of reference ranges should take age and sex variations into account. SUBJECTS AND METHODS: 396 healthy subjects were recruited (172 males and 224 females). Fasting plasma homocysteine levels were measured using the fluorescein polarization immunoassay technique (FPIA). Plasma levels of creatinine, folates, vitamin B-12 and TSH were measured. 90% reference ranges were estimated by fractional polynomial regression methods. RESULTS: Homocysteine plasma levels ranged from 4.35 mu mol/l to 17.71 mu mol/l (median 8.62 mu mol/l). These concentrations increased with age and were higher in males (median 9.53 mu mol/l [range: 5.45-17.5]) than in females (median 7.79 mu mol/l [range: 4.35-17.71]). Sex differences decreased in the elderly. Creatinine plasma levels (with a positive association) and folate levels (with a negative association) had a statistically significant effect on the specific distribution of homocysteine levels according to age and sex. CONCLUSIONS: Age- and sex-specific reference ranges of plasma homocysteine have been defined. Renal function along with folate plasma levels have to be accounted for when assessing these distribution ranges.