The Consensus Statement from the European
Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that
low-density lipoprotein (
LDL) causes atherosclerotic
cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting
LDL receptor function were found to cause higher or lower
LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of
statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of
LDL-C exposure and ASCVD risk. The EAS Statement proposes that any mechanism of lowering plasma
LDL concentration should reduce the risk of ASCVD events proportional to the absolute reduction in
LDL-C and the cumulative duration of exposure to lower
LDL-C. However, as we explain, we do not find this conclusion acceptable.
SUMMARY: Our review points out that different interpretations are possible for the results of Mendelian randomization studies. As for prospective cohort studies, many inconsistent reports on the association of
LDL-C and ASCVD were disregarded when drafting the Statement, reports with and without genetic factors related to
LDL receptor function should be analyzed separately, and the term ASCVD in the Statement is used inappropriately because
myocardial infarction and
cerebral infarction differ in their association with
LDL-C. As for RCTs, clinical reports on
statins published before and after the implementation of new regulations affecting clinical trials (2004/2005) should not both be included in meta-analyses because the evaluated efficacy of
statins changed markedly, and the irreversible adverse effects of
statins need to be evaluated more rigorously now that their mechanisms have been elucidated. Key Messages: Apart from the EAS hypothesis that
LDL causes ASCVD, recent pharmacological/biochemical studies, as summarized in this review and elsewhere, have revealed that
atherosclerosis is caused by
statins taken to lower
LDL-C, as well as by
warfarin and some types of vegetable
fats and
oils, in the absence of significantly elevated
LDL-C levels. Thus, the promotion of
statin treatment by the Statement is rather risky and we do not feel that the conclusions are justified for the prevention of ASCVD.