Total Cholesterol: Pointless Biomarker?

The diet heart hypothesis states that dietary cholesterol is the cause of elevated plasma cholesterol and this in turn causes cardiovascular disease. Over the last two decades the nutritional sciences have demolished this theory which can no longer be regarded as valid, based on evidence in the literature. The realisation that plasma lipoproteins are not the cause of cardiovascular disease, but merely associated with it, is one line of reasoning that argues against the theory. However, more importantly, the idea that plasma cholesterol is carried by a number different classes of lipoproteins, which show differing atherogenic properties, argues against plasma cholesterol as the cause of cardiovascular disease and against total cholesterol use as a reliable biomarker. The overly simplistic traditional view that raised levels of total cholesterol are detrimental to the health is therefore provably erroneous. More detailed analysis of the sub-fractions of various lipoproteins is therefore warranted.

That elevated levels of total HDL-cholesterol are protective of cardiovascular disease has been extensively reported. Elevated levels of HDL are protective of cardiovascular disease, whereas elevated levels of intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and very low density lipoprotein (VLDL) increase cardiovascular risk. This suggests that it is the ratios of the atherogenic to non-atherogenic lipoproteins that are important, not the total concentrations. Original research from the 1950’s showed that HDL was divided into two sub-classes, HDL2 and HDL3. High density lipoprotein 2 is a more buoyant particle, concentrations of which are 50 % higher in women. Some evidence suggests that altered ratios of HDL2 and HDL3 might modify cardiovascular risk, and that measurements of the HDL2 and HDL3 sub-fractions might provide more accurate risk analysis for cardiovascular disease compared to total HDL-cholesterol. However, this information has not yet reached the mainstream.

Researchers1 have investigated the effects of lipoprotein mass concentrations on all cause and cardiovascular mortality using data from a 53 year follow-up of 1905 men. Lipoprotein mass was assessed via ultracentrifugation and cause of death was assessed by medical records or the National Death Index. Of 1329 subjects who had died, 409 had been recorded as due to cardiovascular disease. Following statistical adjustment for age, those in the lowest quartile for HDL2 had a 22 % increase in all cause mortality, 63 % for cardiovascular mortality, and 117 % for premature cardiovascular mortality risk. Following adjustment for total HDL concentrations, this statistical significance remained almost unchanged. When adjusted for age, HDL3 concentration also significantly reduced the risk of cardiovascular mortality, but not total mortality. The results suggested that most of the mortality risk fell within the lowest HDL2 quartile, indicating that HDL2 is more protective of cardiovascular disease than HDL3.

In addition to the HDL sub-fractions the researchers also investigated other lipoproteins and their associations with cardiovascular mortality. Elevated LDL, IDL, small dense VLDL and large dense VLDL all increased the risk of cardiovascular mortality significantly.  These results taken as a whole support the contention that LDL, VLDL and IDL, when elevated, increase the risk of cardiovascular mortality, but that elevated levels of HDL, particularly the HDL2 fraction, are protective. Care should be taken during the interpretation of this data however, as static lipoprotein concentrations taken 6 decades ago may not accurately reflect the dynamic lipoprotein concentrations in the intervening time period. However, despite this limitation, these results add further complexity to the lipoprotein cardiovascular disease association and suggest that HDL2 and HLD3 should be measured independently for a more accurate risk assessment.

RdB

1Williams. P. T. 2012. Fifty-three year follow-up of coronary heart disease versus HDL2 and other lipoproteins in Gofman’s Livermore Cohort. Journal of Lipid Research. 53: 266-272

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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