LDL

LDL is causal to atherosclerosis, John M. Chapman, Paris, France.

• EAS Snapshots
• Τρίτη 21 Νοεμβρίου 2017

Author finds strong evidence for the causality of LDL for CVD

Professor John M. Chapman from Paris, France is a leading scientist in the field of lipoproteins and atherosclerosis. In a presentation given by Professor Chapman entitled: LDL is causal to Atherosclerosis , available on EAS Academy, Professor Chapman summarizes the very large amount of evidence that has accumulated over the years showing, convincingly, that LDL is the major factor causing atherosclerosis.
His lecture is based on a consensus document published by the European Atherosclerosis Society (EAS) summarising current evidence on the causality of LDL for atherosclerotic vascular disease.¹ This publication analyses and summarises more than 200 publications including 20 million patients and 150 000 cases of CardioVascular Disease (CVD). The evidence comes from a variety of different fields of science. A large number of animal models have shown that making animals hypercholesterolaemic, increases the presence of atherosclerosis. A lot of data have accumulated in human epidemiology. Meta-analyses show the consistent relationship between LDL and vascular disease in all ages, in both sexes and in subpopulations.
More recently data from molecular genetics have strongly supported the role of LDL. In Mendelian randomization studies, the association between genetic variations associated with low LDL have shown to be associated with lower risk for CVD. Furthermore, this association is dose dependent; degree of LDL reduction is correlated with degree of CVD reduction. The genetic variation is caused by variation in different genes, coding for proteins in the cholesterol metabolism such as: LDL receptor, HMG-CoA reductase, PCSK9, NPC1L and apoB.
Some of the most convincing evidence comes from the genetic disease familial hypercholesterolaemia, a genetic disorder associated with very high level of LDL and a very high risk for CVD. Other convincing evidence results from a large number of randomized controlled studies showing how reduction of LDL prevents CVD. Many of the studies are using statins for LDL reduction. However, importantly, results from interventions with other drugs, such as ezetimibe or PCSK9 inhibitors, are very consistent with the statin trials.
In his conclusion Professor Chapman refers to the Bradford-Hill criteria for causality.  These criteria look at causality in terms of:  Plausibility, Strength, Biological gradient, Temporal sequence, Specificity, Consistence, Coherence, and/or reduction in risk with intervention. In all these aspects Professor Chapman finds that evidence is strong and the causality of LDL for CVD can be regarded as finally proven.
TO THE PRESENTATATION ONLINE: https://academy.eas-society.org/eas/2017/85th/175505

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