Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: Assessment and implications for epidemiology

An increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have establis hed biovariability characteristics. When biovariability data have been repo rted, they usually represent a short time period, and, in any case, there i s little consensus on how the information should be used. The authors perfo rmed a long-term (6-month) repeated measures study on 26 healthy individual s, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVt), and between individual (CVG) vari ability of 12 procoagulant, fibrinolysis, and inflammation assays, includin g total cholesterol for comparison. The results suggest acceptable analytic al variability (CVA less than or equal to 1/2 CVt) for all assays. However, there was a large range of intraindividual variation as a proportion of to tal variance (2-78%), and adjusting for intraindividual and between individ ual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays show ed a significant increase in intraindividual variation over 6 months (p < 0 .05). While these findings suggest that most of these assays have biovariab ility characteristics similar to cholesterol, there is variation among assa ys. Some assays may be better suited to epidemiologic studies, and knowledg e of an assay's biovariability data may be useful in interpreting simple st atistics, and in designing multivariate models.