Original articles
The homocysteine distribution: (Mis)judging the burden

https://doi.org/10.1016/S0895-4356(00)00341-3Get rights and content

Abstract

The nonfasting plasma total homocysteine (P-tHcy) concentration was measured in a random sample of 3025 Dutch adults aged 20–65 years (main study). The positively skewed distribution had a geometric mean of 13.9 μmol/L in men and 12.6 μmol/L in women. Blood of the main study was not cooled or centrifuged immediately after drawing. A stability study (n = 26) indicated that this could have resulted in a small (0.4 μmol/L) overestimation of the means. A comparative study (n = 88), and a reproduction of these results in an entirely different population (n = 213), showed a systematic difference in P-tHcy concentration of −2.4 μmol/L between our laboratory (Nijmegen, the Netherlands) and that in Bergen, Norway. With the information of the additional studies we provided precise and valid data of the Dutch P-tHcy distribution, from which we conclude the status in the Netherlands is worse than in other European countries. Furthermore, we showed that comparison of P-tHcy data is complicated unless the interlaboratory differences are known. @ 2001 Elsevier Science Inc. All rights reserved.

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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