Underestimation of risk of ischaemic heart disease

Following an old but increasingly popular tradition,6 Law and colleagues corrected the association between cholesterol concentration and risk of ischaemic heart disease for the attenuation (or regression dilution) due to measurement imprecision. Since cholesterol concentrations vary over time, prospective studies relating future risk of ischaemic heart disease to a single measurement will underestimate the true strength of the association. The adjustment is used because few epidemiological studies have obtained repeat measurements. As Spearman noted in 1904,6 however, such adjustments should be used carefully because they are not free of assumptions. They could be misleading if recent levels of a risk factor are more important determinants of disease than earlier levels; if peaks in the level of the risk factor, rather than the usual value, are the important aetiological factor; or if changes in risk factor levels are important.7 Some studies have been able to examine the association of average cholesterol concentration with risk of ischaemic heart disease directly.^8,9 These have indicated that although the correction factors may overestimate the strength of the association between usual cholesterol concentration and risk of ischaemic heart disease, repeated cholesterol measurements identify people at increased risk of disease better than a single measurement.

Law et al have introduced an extension of the correction for attenuation, which they called correction for surrogate measurement bias. Since it is the low density lipoprotein component of total cholesterol which is considered to increase the risk of ischaemic heart disease they argue that the association of total …