Letter From Egom Regarding Article, “High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy”
To the Editor:
In their recent article, Mora et al1 reported that the on-treatment number of high-density lipoprotein (HDL) particles (HDL-P) may be a better marker of residual risk than HDL cholesterol or apolipoprotein A-I.
Although this observation makes a valuable contribution to this field, it is important to emphasize that HDL-P may only give us a small part of the overall HDL picture. Furthermore, some of Mora et al.’s findings must be interpreted with caution because of the potential effect of rosuvastatin on HDL functionality.
In fact, emerging evidence suggests that the overall HDL-P is not as important, as a determinant of residual risk among statin-treated individuals, as the number of HDL-P which contain the lysosphingolipid sphingosine-1-phosphate (S1P).2 This is supported by the evidence that it is the S1P content of HDL, as opposed to the HDL particle itself, which is responsible for the beneficial antiatherothrombotic, anti-inflammatory, antioxidant, antiglycation, and profibrinolytic activities of these lipoproteins.2 Furthermore, an inverse relationship between the level of S1P-bound HDL and the presence and development of CAD exists.2 This suggests that the number of S1P-bound HDL particles may thus provide additional information in residual risk among statin-treated individuals.2
Although limited, emerging data also suggest that rosuvastatin may increase plasma levels of S1P.3 This may result in a higher bioavailability of the substrate for HDL, thus contributing to the S1P content of the HDL particles.2,4 Whether the elevation of the serum S1P after rosuvastatin administration is a class effect or a drug-specific effect remains unknown.5 However, it is important to remember that such an association does not necessarily infer a causal relationship.
Mora et al1 reported that, in the rosuvastatin-treated patients, there was a statistically significant and stronger inverse association of cardiovascular disease (CVD) with HDL-P as compared with the inverse association of CVD with HDL cholesterol or apolipoprotein A-I. However, in patients given placebo, a similar inverse association (similar magnitude) of all 3 parameters with CVD was seen.1 These observations raise the intriguing possibility that the difference in the degree of association with CVD between the 2 groups of population (rosuvastatin versus placebo) may, at least partially, be attributable to the potential effect of rosuvastatin on S1P bioavailability and HDL function.
Emmanuel E. Egom, MSc, MD, PhD, MRCP
EGOM Clinical and Translational
Research Services (ECTRS) Ltd
Halifax, Nova Scotia, Canada
Dr Egom is a recipient of a Heart and Stroke Foundation of Canada Postdoctoral Fellowship.
- © 2014 American Heart Association, Inc.
- Mora S,
- Glynn RJ,
- Ridker PM
- Sugiura T,
- Dohi Y,
- Yamashita S,
- Ohte N,
- Ito S,
- Iwaki S,
- Hirowatari Y,
- Ohkawa R,
- Mishima Y,
- Yatomi Y,
- Kimura G,
- Fujii S