Small, dense low density lipoprotein (LDL) and the insulin resistance syndrome (IRS)

The preponderance of small, dense LDL particles has been termed a conditional cardiovascular risk factor, indicating that data derived from experimental, clinical and intervention studies suggest a strong relation of LDL size and cardiovascular (atherosclerotic) disease (77). However, the lack of randomized, controlled trials showing a beneficial effect of increasing LDL size on cardiovascular disease independent of other known risk factors (including hypertriglyceridemia) precludes the inclusion of small, dense LDL into the category of "causal" risk factors. Accordingly, as of today, LDL particle size can not (yet) be considered a primary target of risk factor intervention, and neither can its routine assessment for clinical purposes be recommended. Numerous studies have unanimously shown that components of the IRS, including insulin resistance itself, constitute major environmental determinants of LDL size. Therefore, therapies aiming at improving insulin resistance have the potential to modify small, dense LDL towards larger, more buoyant particles. Randomized controlled trials investigating the effect of these therapies not only on LDL size but also on clinical (cardiovascular) endpoints will be of particular interest.