Author + information
- Emmanuel E. Egom, MSc, MD, PhD∗ ()
- ↵∗EGOM Clinical and Translational Research Services (ECTRS) Ltd., 5991 Spring Garden Road, Halifax, Nova Scotia, Canada B3H 4R7
In a recent issue of the Journal, Qi et al. (1) demonstrated that high-density lipoprotein cholesterol (HDL-C)/high-density lipoprotein particles (HDL-P) ratio might predict atherosclerotic risk and might explain why high plasma HDL-C levels have failed to avoid ischemic events in some clinical trials. Although the HDL-C/HDL-P ratio may provide a poor and indirect metric for reverse cholesterol transport (RCT), it is important to emphasize that it does not reflect HDL functionality.
HDL-C/HDL-P ratio is a dynamic parameter, which is determined primarily by the HDL-P turnover, especially in a cardiovascular disease–free population. High plasma HDL-P may thus be the major factor predicting atherosclerotic risk, irrespective of plasma HDL-C. High levels of plasma HDL-P may be achieved either by increasing the synthesis rate of HDL-P or by decreasing HDL-P catabolism. Under steady-state conditions, the synthesis rate of a given protein (such as apoprotein A-I) is equal to its turnover. Therefore, an increase in HDL-P synthesis would be more favorable for the overall process of RCT than would the inhibition of HDL-P catabolism, because in the latter mechanism, the HDL-P turnover may be unaffected. Niacin, for instance, may increase plasma HDL-C, at least in part, by preventing HDL-C from being removed by the liver and therefore by blocking HDL-P catabolism (2). This might explain, although only in part, why the recent niacin trials did not provide any cardiovascular benefit.
However, any obstruction or limitation of HDL-P turnover, either as a result of a reduced synthesis or increased catabolism, may negatively affect RCT, and thus lead to more tissue cholesterol deposition. This affirmation is supported by the data of Qi et al. (1) showing no inverse relationship between HDL-C levels and the risk of atherosclerosis progression except for those in the lowest HDL-P subgroups (low synthesis or high catabolism) (1).
Finally, recent evidence also suggests that the overall HDL-P is not as important as a determinant of residual cardiovascular risk as the number of HDL-P, which contain the lysosphingolipid sphingosine-1-phosphate (S1P) (3). Pharmacological agents that increase HDL-P levels by increasing its production in the liver or that improve the functionality of existing serum HDL-P, by increasing S1P uptake, for instance, may be more beneficial.
Please note: Dr. Egom has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Qi Y.,
- Fan J.,
- Liu J.,
- et al.
- Zhang L.H.,
- Kamanna V.S.,
- Zhang M.C.,
- et al.
- Egom E.E.