Optimal time interval between repeated blood sampling for measurements of total homocysteine in healthy individuals

Many studies have shown that increased plasma concentrations of total homocysteine (tHcy) are associated with cardiovascular disease (1). Like most biological variables, plasma tHcy fluctuates within an individual around a long-term mean (2)(3). tHcy measurements often are based on a single blood sample. Taking the mean of two or more repeated measurements will reduce the error attributable to within-subject biological fluctuations and reflect more closely a person’s true mean tHcy value within a certain period. However, as the time interval between two repeated measurements becomes shorter, the values become more similar and the error reduction diminishes. In that case, the benefit of taking the mean of two measurements is not fully used. On the other hand, intervals that are too long (several weeks) may compromise the compliance of study participants and allow long-term seasonal changes (4)(5). Several studies on the weekly and monthly biological variation, as expressed by the CV, in plasma tHcy concentrations have been published (Table 1 ). From these studies, no conclusions can be drawn about the optimal time interval between two repeated samples to obtain a sufficiently precise estimate of the true tHcy concentration within a predefined period. The optimal time interval is reached when the interval-specific CV does not increase further with increasing time interval