Pleiotropic effects and cholesterol-lowering therapy.

Abstract:

:HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors, or 'statins', have revolutionized the management of patients with atherosclerotic vascular disease. Following 2 large acute coronary syndrome trials, additional clinical benefit outside their effect of low-density lipoprotein (LDL) lowering was proposed. This concept was introduced following the observation of cardiovascular event rate reduction, only weeks after initiation of treatment and supposedly before the effect of LDL lowering could have influenced atheroma volume burden. Furthermore, there has been a substantial compilation of experimental data demonstrating beneficial effects of statins on inflammation, thrombosis, platelet aggregation, immunomodulation and endothelial function. These are hypothesized to occur via the interruption of the mevalonate pathway. However, the absolute benefit of these non-lipid-lowering effects, often referred to as 'pleiotropic effects', has been challenged by meta-analysis data. Anti-inflammatory actions have also been proposed to occur by the process of LDL lowering alone rather than due to a unique property of statins. Furthermore, some experimental data reports have shown evidence of pleiotropic effects in non-statin lipid-modifying agents. In this review article, we consolidate what is known so far and critically analyse the literature in order to highlight the outstanding issues.

journal_name

Cardiology

journal_title

Cardiology

authors

Shaw SM,Fildes JE,Yonan N,Williams SG

doi

10.1159/000137692

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

4-12

issue

1

eissn

0008-6312

issn

1421-9751

pii

000137692

journal_volume

112

pub_type

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