Lipids in health and disease

The evidence linking cholesterol levels in the blood to vascular risk is now incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has now revolutionized the management of lipid disorders and silenced at a stroke the critics of cholesterol control as a means to vascular disease prevention. Statins were the first lipid-lowering agents, which, within a framework of a clinical trial, actually extended life by mechanisms that probably go beyond cholesterol alone. Their benefits are so impressive that some enthusiasts have been emboldened to write that they ‘are to atherosclerosis what penicillin was to infectious disease’. But is Nature as easily tamed as we might imagine? Some individuals show a modest or even poor response to statin therapy. The recent discovery of ezetimibe, a highly efficient and precise cholesterol absorption inhibitor, has proven to be a very effective cholesterol lowering alternative for them and combining statins with ezetimibe, thereby inhibiting cholesterol absorption and endogenous synthesis, takes us to realms of cholesterol lowering capability that could not have been dreamt of a decade ago.