Original articlesThe homocysteine distribution: (Mis)judging the burden
Introduction
Accumulating evidence indicates that the plasma total homocysteine (P-tHcy) concentration is an independent risk factor for cardiovascular diseases (CVD) 1, 2, 3, 4, 5, 6, 7, 8. Therefore, it is important that health authorities are provided with information on the possible burden that it might constitute in the general population. For this purpose knowledge on the P-tHcy distribution is necessary. This seems straightforward: provide a laboratory with plasma from a representative population and describe these data. However, some frequently disregarded problems can lead to an incorrect interpretation of the P-tHcy status.
The first problem emerges when a study is not designed to measure the P-tHcy concentration. Optimal blood sampling conditions (i.e., cooling or centrifuging whole blood directly after drawing) [9] are necessary to obtain a valid P-tHcy measurement. Leaving whole blood at room temperature might artificially increase the P-tHcy concentration, which is already detectable after 1 h 10, 11.
A second commonly overlooked problem is that the P-tHcy status cannot simply be evaluated by using reference values established in laboratories other than the laboratory where it was measured. This difficulty is due to the lack of a gold standard and of a (inter)national standardization program for the measurement, which can result in large differences (9–15%) in the P-tHcy concentration of one sample measured in different laboratories 12, 13.
The goal of this article is to provide information on the P-tHcy distribution in the general Dutch adult population (main study), which has been unavailable up until now. To critically judge this distribution we performed a stability study and a comparative study, also described in this article.
Section snippets
Subjects
For the main study we used data from the population-based MORGEN study. This is a cross-sectional investigation into the prevalence of risk factors for chronic diseases as well as the prevalence of some specific chronic conditions, using self-administered questionnaires and a physical examination in a randomly selected sample of the Dutch population aged 20–65 years in three Dutch cities (Amsterdam, Doetinchem, and Maastricht) [14].
From the 19,066 subjects that participated in the MORGEN study
Stability study: the effect of blood sampling conditions on the P-tHcy concentration
Fig. 1 shows the time-dependent change in P-tHcy concentration from baseline, in whole blood stored at room temperature. Already 30 min after baseline we observed a significant mean increase in P-tHcy concentration of 0.41 μmol/L (P = .04). After 90 min the increase in P-tHcy concentration was on average 0.80 μmol/L (P = .0001).
The correlation between the P-tHcy concentration at baseline and at T15, T30, T45, T60, T75 and T90 ranged between 0.95 and 0.97. This indicates that the ranking of the
Discussion
The goal of our study was to provide data on the P-tHcy distribution in the Dutch adult population. Two problems that could hinder a correct judgement of the P-tHcy status were evaluated in the stability and the comparative study. The P-tHcy concentration was skewed towards higher values, the geometric mean P-tHcy level was higher (13.9 μmol/L) in men than in women (12.6 μmol/L) and increased with age. The stability study indicated that our sampling conditions might have caused a mean
Acknowledgements
We thank M.E.P. Hemert-Janssen and S. Houterman for their excellent technical assistance in the stability study, and Prof. H. Refsum, Prof. P.M. Ueland and dr. A.L. Bjørke-Mønsen for the measurement of the P-tHcy concentrations for the comparative study. In addition, we are grateful to Dr. P. Verhoef and K. Lievers for providing data for the reproduction of the comparative study. We thank the field workers of the Municipal Health Services in Amsterdam, Doetinchem and Maastricht for their
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