Plasma creatinine as a determinant of plasma total homocysteine concentrations in the Hordaland Homocysteine Study: Use of statistical modeling to determine reference limits

Objectives: We established population-based reference limits for plasma total homocysteine (tHcy) according to creatinine. Design and methods: In 7042 middle-aged and elderly subjects from the Hordaland Homocysteine Study, we used statistical modeling to establish nomograms for tHcy according to creatinine in the whole population and in folate-replete and healthy subgroups. Results: When plotted against creatinine, tHcy 97.5th percentile almost overlapped in men and women, and, in elderly, increased up to 8 μmol/L from the 2.5th to 97.5th creatinine percentiles. Folate-replete subjects had tHcy upper limits 20% below the whole population at all creatinine levels. Healthy subjects had lower creatinine, but at a given creatinine level, tHcy was the same as in the whole population. Conclusions: tHcy difference between men and women is mostly explained by creatinine. The tHcy-reducing effect of folate is independent of creatinine. In elderly people, creatinine should be taken into account when assessing tHcy levels.