Abstract
Middleton (1) describes the effect of analytical variation in high-sensitivity C-reactive protein and lipid assay on cardiovascular risk calculation, using a Monte Carlo simulation technique and the Ridker-Rifai quintile model, and demonstrates that relative risk is over- or underestimated in a substantial proportion of cases. From this he concludes that multiple HDL-cholesterol estimations may reduce misclassification that occurs because of assay imprecision. This is true, but this approach underestimates the imprecision of risk calculation. The factor that is neglected in this investigation of the precision of risk estimation is the important role played by biological variation. We have recently published a similar analysis scenario in which we mathematically modeled a hypothetical “True” population derived from data from the National Health Survey for England. We investigated the effect of combined biological and analytical variation in total cholesterol and HDL-cholesterol, as …
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