Elevations in plasma lipid levels are often mistakenly described as the caused of cardiovascular disease. However, research does not support this contention. Elevations in certain plasma lipids have been shown in research to be a risk factor for cardiovascular disease, but the cause and effect has not been established. In fact while the association between elevations of certain plasma lipids and cardiovascular disease is present for certain subgroups of population, the association is not present for other groups. Therefore we can establish that the use of cholesterol and triglyceride levels as a predictive tool for cardiovascular disease is controversial. In fact controversy also exists as to which plasma lipid measurement is the best predictor of cardiovascular risk. In fact, recent research has moved away from the use of plasma lipids, in favour of other biomarkers including homocysteine, C-reactive protein and the degree of endothelial dysfunction.
Traditionally, the plasma levels of total cholesterol were considered to be a useful diagnostic tool to predict cardiovascular disease risk, but mounting evidence suggests that this biomarker is not reliably predictive of cardiovascular risk. In fact, further work has showed that total cholesterol levels are much less useful that the low density lipoprotein (LDL) to high density lipoprotein (HDL) ratio. This is because while high levels of LDL appear to increase the risk of developing cardiovascular disease, high levels of HDL appear to reduce the risk. Therefore it is the ratio of the two blood lipids that is important in establishing the risk of cardiovascular disease. This is based on the purpose of these lipoproteins within normal physiology. For while LDL can transport cholesterol from the liver to the peripheral tissues such as the endothelial lining of arteries, HDL can transport this cholesterol back to the liver for excretion.
However, the LDL to HDL cholesterol ratio does not take into account other blood lipids, that may also be a risk factor for cardiovascular disease. Recent studies have found that the plasma levels of apolipoprotein (apo) B, and more specifically the ratio of apo B to apo A-1, may be a more accurate predictor of cardiovascular risk. This is because the atherogenic particles, that could be considered LDL, very low density lipoprotein (VLDL; triglycerides) and the intermediate density lipoprotein (IDL) all possess the apo B molecule. However, the HDL cholesterol particle, the anti-atherogenic particle, contains the apo A1 particle. By measuring the ratio of apo B to apo A1, a ratio of the atherogenic to anti-atherogenic particles in the plasma can therefore be calculated. Therefore the number of atherogenic to anti-atherogenic particles in plasma can provide a comprehensive determination of cardiovascular risk. The apolipoproteins present on the various plasma lipoproteins are shown in figure 1.
Figure 1. The maim lipoproteins and their composition.
However, the risk of cardiovascular disease based on plasma lipid measurements is further complicated by sub-groups of LDL particles. Researchers have identified two main sizes of LDL particle, which can modify cardiovascular risk depending on the concentrations of each in plasma. Small dense LDL particles have been shown to increase the risk of cardiovascular disease to a greater extent than larger, less dense LDL particles. The smaller particles are thought to be able to more easily penetrate the endothelial lining of the arteries and therefore are more likely to be involved in the development of an atherosclerotic plaque. Having predominately small dense LDL particles is termed pattern B, whereas having predominately larger and less dense LDL particles is termed pattern A. Pattern I (intermediate) corresponds to LDL particle sizes predominately in between pattern A and B. Pattern B LDL increase cardiovascular risk above pattern A LDL, even if the latter has more total particles.
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