Editorial Does Measurement of Apolipoprotein B Have a Place in Cholesterol Management?

In the accompanying editorial, Sniderman and Silberberg raise the question, "Is It Time To Measure Apolipoprotein B"? If this question means whether it is time to measure apolipoprotein B-100 (apo B) clinically to estimate the risk for coronary heart disease (CHD) or to guide in lipid-lowering therapy, our answer is an unqualified "No." Whether measurement of apo B will prove valuable in the future is another question; the answer is "Maybe." Sniderman and associates made an important contribution with the recognition that some patients have high concentrations of apo B in the presence of "normal" serum cholesterol levels. Without question, low density lipoprotein (LDL) apo B levels can be disproportionately high compared to cholesterol levels. The condition of elevated LDL apo B and normal LDL cholesterol they called "hyperapobetalipoproteinemia." In their initial definition, "elevated" apo B was confined to the LDL fraction. More recently, their definition seemingly has been expanded to include serum total apo B, and a simple term for high total apo B is "hyperapo B." Total apo B includes apo B in LDL, intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL). For each of these classes, there is one molecule of apo B per lipoprotein particle; hence, measurement of total apo B concentration yields the total number of apo B-containing lipoproteins in a volume of plasma. The critical question raised by the research of Sniderman et al . 3 is whether total apo B levels better predict CHD than does the total cholesterol level or another cholesterol parameter. What are the data related to this question? The evidence is based on small, retrospective studies and not on large, prospective studies. The latter are required before apo B determination can be considered superior to cholesterol measurement. Retrospective surveys are notorious for giving suggestive evidence that is not confirmed by large prospective studies. At this time, therefore, we cannot assume that total apo B is better than total cholesterol for detection of high-risk individuals. Moreover, the predictive power of total cholesterol measurement is enhanced by adding triglycerides, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, and cholesterol ratios. To justify introducing complex and expensive new methodology for apolipoproteins, it must be demonstrated that the total apo B level is definitely superior to total lipids and lipoprotein cholesterols for predicting CHD risk or for monitoring therapy. In recommending total apo B measurements, Sniderman and Silberberg seemingly postulate that all apo Bcontaining lipoproteins are similarly atherogenic. Accordingly, one VLDL particle would have the same atherogenecity as one LDL particle, or within the LDL density class, small LDL particles would have similar atherogenecity as large LDL particles. Although this is an intriguing hypothesis, it is not universally accepted. Apo B-containing lipoproteins vary in size, types of apolipoproteins, and contents of apolipoproteins, triglycerides, and cholesterol. It, therefore, would be surprising if all lipoprotein species are equally atherogenic. This conceptual stumbling block probably stands in the way of universal acceptance of total apo B level as a predictor of CHD risk.