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Received wisdom is that cholesterol is a significant risk factor for the development of atherosclerosis, and for coronary heart disease (CHD) in particular. Bowden and Sinatra, in their book The Great Cholesterol Myth1, explain how historically too much importance has been attached to cholesterol as a cardiovascular (CV) risk factor, how lipid-lowering trials have yielded results that have been at best inconclusive, that eating saturated fat actually lowers serum cholesterol, and how occlusive vascular disease arises as a result of endothelial inflammation, an excess of dietary glucose and one’s inadequate reaction to the stresses of life.


Their arguments are, at first sight, quite appealing, although many of the references they cite date from ten or more (sometimes a lot more) years ago. Nevertheless, even with the addition of a dose of healthy scepticism the notion that cholesterol is not the villain it is cracked up to be is thought-provoking.


Cholesterol is a lipid molecule essential to animal life. It enables permeability and fluidity in cell membranes and serves as a precursor for the biosynthesis of steroid hormones, bile acids and vitamin D. It is formed predominantly in the liver. In fact dietary cholesterol is poorly absorbed. The body compensates for absorption of additional cholesterol by reducing cholesterol synthesis. Thus cholesterol intake in food has little, if any, effect on serum cholesterol, which maybe calls into question low-fat/cholesterol diets as CHD risk-reducing measures.


And a little Google-aided independent research reveals that there is much more to the role of lipids in CV risk than total, HDL (‘good’) and LDL (‘bad’) cholesterol and its brother triglyceride:

  • LDL cholesterol has at least six subfractions (LDL I to IV, with both III and IV being subdivided into A and B).
  • There are the apolipoproteins that bind lipids to form lipoproteins. Apolipoproteins come in six varieties (A to E and H, with A to C having ten different sub-categories between them).
  • The lipoprotein subclass Lp(a) – described by Bowden and Sinatra as the “‘alpha-wolf’ of cholesterol particles” – is believed to contribute to blood clot formation. A meta-analysis2 found it to have “continuous, independent and modest associations… with risk of CHD and stroke that appear exclusive to vascular outcomes.”


The roles of these various lipid fractions are not well understood, but it remains to be seen whether more clarity on how they work and interact will affect our view of lipids in the spectrum of CV risk factors and of strategies for disease prevention – and of course currently lipid-lowering plays a key part.


But it is interesting to note that in the Framingham CHD risk-scoring model cholesterol is not that high-scoring a risk factor. Fulks and colleagues3 reported that “total cholesterol/HDL ratio is the best single measure of all-cause mortality risk among the various lipid tests but is useful only if viewed on an age- and sex-specific basis and is only a modest risk predictor (our italics).”


An investigation based on the Norwegian HUNT 2 study4 found in men a weakly positive correlation between serum cholesterol and CV disease, and a U-shaped pattern. Among women, cholesterol had an inverse association with all-cause and CV mortality. The authors concluded that if their findings “are generalizable, clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.”


Various other journal articles point to cholesterol having little significance at older ages and to low levels being associated with an excess of deaths. Perhaps the strongest case for not pinning too much faith on cholesterol is that most individuals with CHD have normal serum cholesterol levels. (Bowden and Sinatra say that if you are going to measure anything, go for triglyceride/HDL ratio.)


Now, we are not suggesting you discard cholesterol as an underwriting factor or modify your definitions for preferred and the associated rating algorithms. But this, as we said earlier, is thought-provoking stuff:

  • The formation of atheroma and the development of intra-arterial conditions that create a high risk of occlusion are highly complex multi-factorial processes. It would not be unreasonable to think that cholesterol likely plays only a small part in these.
  • Likewise lifestyle (including diet) and genetic susceptibility probably play a very significant part in the genesis of CHD etc. But it is very difficult to measure these risks objectively and reliably.
  • Is lipid-lowering statin therapy an expensive way of having a small impact on CV disease mortality and morbidity? Could those dollars be better spent someplace else?
  • If you are getting a blood sample to analyse you might as well check out the various lipid fractions. But if you are obtaining a sample especially for cholesterol etc, is it really worth it?
  • Coronary calcium scoring, carotid ultrasound scanning and maybe other techniques are far better indicators of CV risk than blood lipids. Even now there are NT-proBNP and CRP that predict CV risk (though CRP alone is not reliable), and gamma-GT is becoming recognized now more as an indicator of CV risk than liver disease or alcohol intake.
  • At the moment lipid profiling is far cheaper but when the costs of much more effective tools that noninvasively visualize arterial disease have fallen, as they will do, will cholesterol become one of those quaint old tests we used to do?


It does make you think, doesn’t it?



  1. Bowden J, Sinatra S. The Great Cholesterol Myth. Fair Winds Press. Beverly, USA. 2012
  2. Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009 Jul 22;302(4):412-23
  3. Fulks M, Stout RL, Dolan VF. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants. J Insur Med. 2009;41(4):244-53
  4. Petursson H, Sigurdsson JA, Bengtsson C, Nilsen TI, Getz L. Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. J Eval Clin Pract. 2012 Feb;18(1):159-68