Does LDL Particle Size Matter?
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: El Harchaoui K, et al. Value of Low-Density Lipoprotein Particle Number and Size as Predictors of Coronary Artery Disease in Apparently Health Men and Women. J Am Coll Cardiol. 2007;49:547-553.
Small dense low-density lipoprotein cholesterol (LDL-C) particles are believed to be more atherogenic than large ones. Nuclear magnetic resonance spectroscopy (NMRS) is a new method that can measure low-density lipoprotein particle number (LDL-P) and size. Thus, these investigators used the prospective Norfolk, England, population study to perform a nested case-control analysis of the association between LDL-P and size with LDL-C and the risk of future coronary events. The Norfolk study consisted of 25,663 people between ages 45 and 79 years who attended a clinic visit. The main objective of the study was to investigate the relationship between diet and cancer, but additional data were collected to look at other diseases. Death and hospitalization data were available through the National Heath Service database. Patients with known coronary artery disease (CAD) on the first visit were excluded, and no one was on a statin at baseline. For each case that developed fatal or nonfatal CAD, one or 2 controls were matched for age and sex. Follow-up was for 6 years. Results: CAD developed in 1,003 who were matched with 1,885 controls. Cases were more likely to be smokers, diabetic, and hypertensive or obese as compared to controls. Also, LDL-C triglycerides and non-high-density lipoproteins (HDL) levels were higher in cases and HDL-C was lower as compared to the controls. LDL-P was higher in cases and the cases had more intermediate and small-sized particles. Since the level of large-sized particles was not different between the 2 groups, the increase in LDL-C in the cases was due more to smaller particles. All 5 lipid/lipoprotein measures (LDL-C, LDL-P, HDL-C, triglycerides and non--HDL-C) were correlated with future CAD events in an univariate analysis. LDL-P and HDL-C were the most potent predictors. A multivariate analysis that corrected for the other lipid parameters showed that the additional value of LDL-P was lost after adjustment for HDL-C and triglycerides and the value of particle size was abolished after adjustment for LDL particle number. In a model that adjusts for the Framingham risk score, LDL-P and HDL-C retain their ability to predict CAD, but LDL-C does not. The authors concluded that NMR determined LDL-P predicts CAD after adjustment for Framingham risk score and LDL cholesterol levels, but its value was abolished after adjusting for HDL-C and triglycerides.
Commentary
Clinicians have been frustrated because LDL cholesterol does not explain all of the lipoprotein associated risk for CAD and there has been considerable debate over what is the best secondary treatment target after LDL is optimized. In fact, in patients withelevated triglycerides, diabetes or the metabolic syndrome, increased particle number is not reflected in LDL levels. These are patients where secondary goals may be most useful. In this study LDL-P and HDL-C improved the risk prediction for CAD over LDL-C. LDL particle size did as well, but when corrected for LDL-P the predictive value of particle size was abolished. When HDL-C and triglyceride levels are considered, the predictive value of LDL-P size is lost. Thus, HDL-C may be the best secondary target of therapy.
Other studies have suggested that apolipoprotein B (apoB) or non-HDL-C may be a better secondary predictor of CAD. ApoB was not assessed in this study, but non-HDL-C did improve upon the risk prediction of the Framingham score and was highly predictive of events in the multivariate model. Thus, at this point measuring LDL particle size does not seem to add much to standard clinical and lipid/lipoprotein measures and cannot be recommended as a routine test. There are some limitations to this study. The patients were older and had higher LDL-C levels than expected for a general population. So the results may not apply to young subjects with lower LDL-C. Control subjects could have had sub-clinical CAD since no exclusionary testing was done. Also, CAD events could have been underestimated using death reports and hospital records. Regardless, this study provides no compelling evidence that LDL particle size or number should be routinely assessed. If available, this testing may be of value as a secondary target in high-risk patients who have had their LDL-C lowered. However, other measures may be equally valuable in this regard, such as HDL-C, non-HDL-C, and triglycerides.
Small dense low-density lipoprotein cholesterol (LDL-C) particles are believed to be more atherogenic than large ones.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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