Atherosclerosis development: lipoproteins and beyond
Even the most sceptical cardiovascular scientists can now rest assured: LDL demonstrates a causal relationship to atherosclerotic cardiovascular disease (CVD) [1▪▪]. A combined dataset of meta-analyses of over 200 cohort-based, mendelian randomization, and randomized trials covering 2 million subjects, followed for more than 20 million person years with more than 150 000 major adverse cardiovascular events (MACEs) showed 1) a dose-dependent linear relationship between LDL-c levels and MACE, and 2) if LDL plasma particles are reduced without off-target effects, the risk of MACE is reduced. This is timely news in light of recent clinical outcomes concerning a new type of LDL-lowering compound, proprotein convertase subtilisin/kexin type 9 (PCKS9) antibody inhibitors, such as evolocumab, bococizumab, and alirocumab [2–4]. These antibodies prevent degradation of the LDL receptor, lower plasma LDL by ∼60% on top of statin treatment, and associated MACE by 15% (reviewed in ). Although this represents one of the most effective and fastest developments in recent years, it remains that 74 patients need to be treated with evolocumab to prevent one major event. This leaves considerable room for new therapeutic approaches. This could possibly be provided by anti-inflammatory treatment, such as IL1-β inhibitor canakinumab, clinical results of which are eagerly awaited at ESC 2017 [6,7]. Nevertheless, more insight in the pathogenesis of atherosclerosis is still warranted and a welcome recommendation on the design, execution, and reporting of murine atherosclerosis studies will ensure reproducibility of animal pathogenesis studies and, hopefully, improve translation of mechanisms to human disease [8,9▪▪].