Triglyceride-rich lipoprotein cholesterol and cardiovascular risk

The triglyceride-rich apoB lipoprotein particles make up a minority of the apoB particles in plasma. They vary in size, in lipid, and in protein content. Most are small enough to enter the arterial wall and therefore most are atherogenic. But how important a contribution TRL particles make to the total risk created by the apoB lipoproteins remains controversial. A recent Mendelian randomization analysis determined that the cardiovascular risk related to the cholesterol within these apoB particles--the TRL cholesterol--was greater than--and independent of--the risk related to apoB. If correct, these observations have major clinical significance.

Accordingly, we have analyzed these results in detail. In our view, the independent strength of the association between TRL cholesterol and apoB with cardiovascular risk seems inconsistent with the biological connections between apoB and cholesterol as integral and highly correlated constituents of apoB particles. These results are also inconsistent with other lines of evidence such as the results of the fibrate randomized clinical trials. Moreover, we are also concerned with other aspects of the analysis.

We do not regard the issue as settled. However, this enquiry has led us to a fuller understanding of the determinants of the cholesterol content of the TRL apoB particles and the complex processing of cholesterol amongst the plasma lipoproteins.