Editorials

Is good cholesterol always good?

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.329.7464.471 (Published 26 August 2004) Cite this as: BMJ 2004;329:471
  1. Gilbert R Thompson, professor (g.thompson@imperial.ac.uk)
  1. Metabolic Medicine, Imperial College, Faculty of Medicine, Hammersmith Hospital, London W12 0NN

    Genetic and pharmacological increases of HDL cholesterol need further evaluation

    Cholesterol has an essential physiological role in humans, but an excess is pathogenic. Its metabolism is regulated by various enzymes, receptors, and transfer proteins present in the small intestine, liver, peripheral cells, and plasma. Cholesterol is secreted from the liver into plasma as very low density lipoprotein (VLDL), which gets converted to low density lipoprotein (LDL). LDL cholesterol is a risk factor for coronary heart disease, hence its synonym—bad cholesterol. High density lipoprotein (HDL) helps to carry cholesterol mobilised from peripheral cells and destined for disposal by the liver, a process termed reverse cholesterol transport. This role and epidemiological evidence that the concentration of HDL cholesterol in plasma correlates inversely with risk of coronary heart disease have earned it the reputation of being “good” cholesterol.1 The recent report of a drug that markedly raises HDL cholesterol by interfering with reverse cholesterol transport poses the question whether this method of increasing HDL will prevent or promote coronary heart disease.2

    The new drug, torcetrapib, raises HDL cholesterol by inhibiting cholesterol ester transfer protein (CETP), which mediates reverse cholesterol transport (figure). A recent study shows that almost 40% of the variation in HDL cholesterol between individuals is genetically determined, one quarter of …

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