Low-density lipoprotein lowering and atherosclerosis progression: does more mean less?

Abstract

Statins (hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) have been shown to significantly reduce cardiovascular clinical events in a variety of patient categories, ranging from patients with established cardiovascular disease to those at risk for cardiovascular disease.1–6⇓⇓⇓⇓⇓ Clinical benefits of statin therapy have also been shown across a wide range of pretreatment cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, warranting recent recommendations that statin therapy should be considered in all high-risk subjects, regardless of baseline cholesterol levels.6 While it is generally agreed that most of the clinical benefits of statins are related to cholesterol/LDL-C 2lowering, other biological effects of statins that do not depend on LDL-C lowering, the so-called pleiotropic effects, including effects on non-LDL lipid fractions, have also been implicated, mostly based on indirect data and preclinical findings.7,8⇓ Two important questions with respect to the statins are 1) is the magnitude of clinical benefit from statins related to the magnitude of LDL-C lowering or, in other words, does a lower LDL-C mean greater benefit, and if so, what is the lowest LDL-C level below which no further benefit can be expected? and 2) do statins differ from each other in terms of clinical benefit, and if so, is that related to unique properties of a statin or simply due to differing potencies in LDL-C lowering? See p 2055 In this issue of Circulation , Taylor and colleagues9 attempted to address the issue of magnitude of LDL-C lowering and its effect on changes in carotid-intima media thickness (IMT) in a cohort of patients with …