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Sir,—The data on low density lipoprotein (LDL) concentrations in table 2 of the paper by Mendall et alappear to be flawed.1 Assuming that the values given for LDL and high density lipoprotein are expressing the concentration of cholesterol in each lipoprotein fraction, and assuming that the triglyceride median value is close to the geometric mean, then the calculated mean value of LDL cholesterol using the Friedwald equation2 would be 4.22 mmol/l, not 1.47 mmol/l. The latter concentration is so low as to be in the range seen in subjects with hypobetalipoproteinaemia.3 Thus the lack of any relation between interleukin 6 or tumour necrosis factor α and LDL cholesterol in this study may have been spurious. If, as suggested by the authors, raised cytokines in the blood are a reflection of the atherosclerotic process, it is possible that they would have shown a relation between cytokines and the concentration of LDL cholesterol (not just with triglyceride) if this had been calculated correctly.
This letter was shown to the authors, who reply as follows:
The LDL cholesterol was indeed miscalculated. The coefficients in table 2 should actually be 0.032 for tumour necrosis factor α (95% confidence limits −0.126 to 0.190) and 0.015 for interleukin 6 (95% confidence limits −0.117 to 0.196). Both of these associations are weak and not significant.
We offer two, rather than one, possible explanations for the association of serum cytokine concentrations with evidence of coronary disease and cardiovascular risk factors. The first is that they are an epiphenomenon of the atherosclerotic process, and the second that they, either directly or through an effect on many conventional cardiovascular risk factors, play a role in the pathogenesis of atherosclerosis. It is still possible for the cytokines to be related to the atherosclerotic process without necessarily being associated with LDL cholesterol. LDL cholesterol may be associated with a different aspect of the pathogenesis of atherosclerosis from that indicated by these particular cytokines.