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Statin treatment and the risk of recurrent pulmonary embolism

Kausik K. Ray
DOI: http://dx.doi.org/10.1093/eurheartj/eht124 1775-1777 First published online: 13 April 2013

This editorial refers to ‘Statin treatment and the risk of recurrent pulmonary embolism’, by S. Biere-Rafi et al., on page 1800

Statin treatment is well established for the primary and secondary prevention of atherothrombotic disease in the coronary and cerebral arterial circulation.1 Cholesterol and in particular LDL-cholesterol (LDL-C) is log linearly associated with risk of fatal and non-fatal myocardial infarction; therefore, not unsurprisingly, the benefit of statins on coronary heart disease (CHD) risk appears to be log-linear, with about a one-fifth to one-quarter lowering of CHD risk per 1 mmol/L lowering of LDL-C.1 Whilst the relationship between the effect of cholesterol and LDL-C on incident stroke is less clear, there is clear evidence that statins reduce stroke by about one-fifth, raising the possibility that the clinical benefit may be unrelated to lowering of LDL-C. Statins block hydroxymethylglutaryl (HMG)-CoA reductase, which is a rate-limiting enzyme not only for the production of cholesterol via the squalene pathway but also for the generation of several isoprenoids such as geranyl geranyl pyrophosphate and farnesyl pyrophosphate which prenylate small molecules such as Rho and Ras involved in particular with inflammatory cell signalling, thus leading to activation of various transcription factors.2 These non-LDL- C-dependent but HMG-CoA-related effects have often been referred to as pleiotropic effects and, whilst readily demonstrated in vitro, the clinical relevance of these effects have never been conclusive. Several observational studies and post-hoc data from randomized controlled trials have suggested a range of benefits on cardiovascular disease and the vascular system, from favourable effects on renal function, to favourable effects on heart failure among those with CHD,3 which appear unrelated to effects on LDL-C. It is not surprising, therefore, that interest has focused on venous thrombo-embolic disease