‘Good’ cholesterol theory questioned

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6 June 2012

It has been known for many years that there is an inverse association between the plasma concentration of high density lipoprotein (HDL) cholesterol and the risk of having a heart attack: the higher the concentration, the lower the risk and vice versa. HDL is thought to be beneficial by removing cholesterol from tissues and carrying it to the liver for disposal. HDL cholesterol was called ‘good’ cholesterol because it was thought to cause the reduced risk of heart attack. However, evidence has accumulated that this is not the case.

There have been three large studies of inherited variations in gene composition that increase plasma concentrations of HDL cholesterol without affecting low density lipoprotein (LDL) cholesterol or triglycerides, both of which are known risk factors for heart attack. Two studies, from Professor Børge Nordestgaard and colleagues in Copenhagen, were published in the Journal of Clinical Endocrinology & Metabolism (JCEM ) on 1 April 2009 and 1 December 2010. The first found that the frequency of a hepatic lipase genetic variant in 2,110 heart disease patients and 4,899 control subjects did not differ. The second measured the frequency of an apolipoprotein A1 genetic variant in 2,361 heart disease patients and 10,273 controls. Again there was no difference. The third study, from Dr Benjamin Voight of Philadelphia and a very large number of national and international colleagues, was published online in the Lancet on 17 May 2012. They pooled 20 studies of an HDL-increasing variant of the endothelial lipase gene with a total of 20,913 heart attack patients and 95,407 controls. The gene frequency did not differ between the two groups.

Professor Nordestgaard and colleagues have also studied the converse: a variation in the lecithin-cholesterol acyltransferase gene that is associated with a lowered plasma concentration of HDL cholesterol. Their study of 54,500 individuals was published in JCEM on 1 February 2012. While low HDL cholesterol concentrations were strongly associated with heart attacks, genetically decreased values were not.

The absence of a cause and effect relationship with heart attack does not mean that measurement of plasma HDL cholesterol is of no value. Although not causal, low values remain a marker of risk. As we reported in a 2008 News item, this is true even in patients whose high level of ‘bad’ LDL cholesterol has been lowered by treatment with drugs (statins). We repeat that it would seem prudent for everyone to maintain life style factors that have a beneficial effect on risk: not smoking, maintaining a normal body weight and taking regular exercise.