I think the article by Ference et al in JAMA Jan 29, 2019 is extremely interesting because it helps explain the role of TGs in coronary heart disease. Here are my comments on the article.
Getting a B (as in Apolipoprotein B) Is Good Enough
Clinicians and researchers have debated the role of triglycerides (TGs) in atherosclerosis and coronary heart disease (CHD) since Steven Hulley argued argument against their role in 1980.1 Ference and colleagues have now, in my opinion, settled the issue.
These authors used lipid, genetic, and outcome data from 654,783 participants from multiple sources to examine the relationship between genes encoding for the LDL receptor (LDLR) and those encoding for the enzyme lipoprotein lipase (LPL). LPL is a critical enzyme in triglyceride metabolism because it removes TGs from the VLDL particle, thereby transforming these particles into LDL and enabling their clearance by the LDL receptor.
The authors created an LPL and LDLR genetic score for each of the genes encoding for lower TGs or lower LDL values. As expected, the LPL genetic score was associated with lower TGs and slightly higher LDL cholesterol values, whereas the LDLR genetic score was associated with lower LDL and slightly lower TGs. When both the LPL and LDLR scores were matched for the magnitude of their apolipoprotein B (Apo B) reduction, there was no difference on their effect on CHD outcomes. In other words, after adjusting for these genes’ effects on ApoB, neither the LDL nor TG were related to CHD outcomes. Because each “bad” cholesterol particle, whether it’s a VLDL or LDL particle, has one ApoB, this suggests that the real culprit is the number of lipid particles. So, TGs are a risk marker for CHD because they indicate increased atherogenic ApoB-containing particles.
The key clinical implications of these findings are that TGs are a risk marker for CHD and that ApoB levels are a more accurate measurement of that risk than TGs alone because ApoB indicates the number of atherogenic particles. Consequently, ApoB measurement is the key measurement of atherosclerotic risk. Also, because the amount of TGs associated with each ApoB is large, large reductions in TGs are required to reduce ApoB levels and to approximate the magnitude of benefit achieved by lowering LDL. This helps to explain why the relatively small reductions in TGs in prior studies failed to reduce CHD events. These results explain the role of TGs and also why there has been such a debate on the issue.
Bottom line? In contrast to what your parents told you, getting a B, as in apolipoprotein B, is probably good enough.
References
- Hulley SB, Rosenman RH, Bawol RD, Brand RJ. Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. N Engl J Med. 1980;302(25):1383–1389. https://www.nejm.org/doi/full/10.1056/NEJM198006193022503
