Education And Debate

Commentary: Disagreements are not substantial

BMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6935.1027 (Published 16 April 1994) Cite this as: BMJ 1994;308:1027
  1. M R Law,
  2. N J Wald
  1. Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, St Bartholonew's Hospital Medical College, London EC1M 6BQ
  1. Correspondence to: Professor Wald.

    George Davey Smith and Matthias Egger agree with the conclusions and recommendations in our cholesterol papers*RF 1-3* and also with our recommendation against mass cholesterol testing.4 They disagree with us on two aspects but these are both minor. One relates to the methods and the other to interpretation. Neither affects the importance of serum cholesterol concentration in the aetiology and prevention of ischaemic heart disease, but both raise issues of general epidemiological application.

    Correction for underestimation in observational studies

    It is well recognised that cohort studies underestimate the dose-response relation between an imprecisely measured risk factor (here serum cholesterol) and its effect (here mortality from ischaemic heart disease).5 The statistical procedure to adjust for this regression dilution bias is simple, accurate, and corroborated by direct measurement.

    Davey Smith and Egger do not give the correct reason for taking account of the second source of underestimation, the surrogate dilution effect. It is not that low density lipoprotein cholesterol measures an effect closer to the target site than total cholesterol. It is because it permits the quantitative reconciliation of data from observational studies with data from randomised trials. In the trials the reduction in total serum cholesterol concentration is almost entirely due to reduction in low density lipoprotein cholesterol because the interventions are relatively specific for this cholesterol subfraction. In the observational studies the variation in total serum cholesterol concentration is not due to low density lipoprotein cholesterol alone. This difference needs to be adjusted for if the two types of studies are to be quantitatively compared.

    The adjustment is small, changing the estimated decrease in mortality from 24% to 27% for a 0.6 mmol/l decrease in cholesterol concentration.1 Davey Smith and Egger acknowledge that the association with ischaemic heart disease must be greater for low density lipoprotein …

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