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30-04-2012 | Cardiometabolic | Article

Particle-based LDL predictors for CV events not better than LDL cholesterol


Free abstract

MedWire News: Measuring plasma apolipoprotein level and low-density lipoprotein (LDL) particle number is of no additional value beyond measuring LDL cholesterol for predicting major occlusive coronary events in high-risk patients, report researchers.

"There was no clear evidence in this large study of a difference in the strengths of the associations of any of the particle or cholesterol-based LDL related measures with major occlusive coronary events or revascularization," say Sarah Parish (University of Oxford, UK) and colleagues.

Although LDL and high-density lipoprotein (HDL) are traditionally quantified by measuring the cholesterol they contain, inter-individual variations in the cholesterol content of LDL and HDL particle could mean that alternative analytic measures are more informative, explain the authors. However, previous research does not consistently support the additional value of such measures when added to standard lipid profiling.

The team therefore assessed data from the Medical Research Council/British Heart Foundation Heart Protection Study, in which a total of 20,536 individuals were randomly assigned to receive either 40 mg simvastatin daily or matching placebo for approximately 5 years and were followed up for incidence of coronary events.

All participants had a baseline non-fasting blood total cholesterol concentration of at least 3.5 mmol/L and either a previous diagnosis of coronary heart disease, cerebrovascular disease, other occlusive disease of non-coronary arteries, diabetes Type 1 or 2, or were men aged older than 65 years undergoing treatment for hypertension.

The researchers evaluated the association of baseline cholesterol fractions, apolipoprotein (apo) B and A1, and lipoprotein particle number (LDL-P) with coronary events among the participants over a mean follow-up period of 5.3 years.

As reported in Circulation, 1796 participants suffered a major occlusive coronary event, 2187 had a revascularization, 1043 had another cardiac event, and 995 had a presumed ischemic stroke.

The researchers found that major occlusive coronary event and revascularization showed equally strong associations with all four LDL-related measures. For each 1 standard deviation increase in LDL-cholesterol, non-HDL cholesterol, apolipoprotein B, and LDL-P, the adjusted hazard ratios for major occlusive coronary events were 1.25, 1.22, 1.23, and 1.25, respectively.

Findings were similar for revascularization and for the combined outcome of major occlusive coronary event or revascularization.

Furthermore, an analysis of LDL-P by particle size, (LDL-Psmall =18-21.2 nm and LDL-Plarge = 21.2-23 nm) showed that the strength of the association between major occlusive events with the three LDL subclasses combined was the same as that for LDL-P alone, indicating that the LDL subclasses did not contribute any additional predictive value over LDL-P.

In an accompanying editorial, Ira Ockene (University of Massachusetts, Worcester, USA) says the evidence "does not support measurement of apolipoproteins and particle subclasses as adding meaningfully to our ability to predict risk of atherosclerosis disease."

"The tools we have available to define cardiovascular risk are quite adequate; we now need to improve their utilization so as to further reduce the population burden of cardiovascular disease," he adds.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Sally Robertson