European Atherosclerosis Society (EAS) Consensus Panel - 2017
LDL causes ASCVD - EAS Consensus Statement (Part 1: genetic, epidemiologic, and clinical evidence)
Recommendation
LDL should be regarded as a cause of atherosclerotic cardiovascular disease, not merely a biomarker, and lowering LDL particle exposure (by amount and duration) is expected to reduce ASCVD risk proportionally.
What it is based on
The statement rests on triangulation across three evidence types appraised against causality criteria: Mendelian randomization (lifelong genetically lower LDL tracks lower ASCVD risk), randomized trials (lowering LDL by any mechanism reduces events proportional to the absolute reduction), and large prospective cohorts - more than 2 million participants and 150,000+ events showing a consistent dose-dependent, log-linear LDL-risk relationship.
- Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis
- Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials
How skeptics respond
Skeptics argue the consensus overstates certainty: that Mendelian randomization is confounded by pleiotropy and is not equivalent to mid-life drug therapy (canalization); that randomized-trial benefit is reported in relative rather than absolute terms; that the elderly cholesterol paradox is unexplained by a simple causal model; and that the panel's pharmaceutical ties bias the framing. It is also noted the statement does not address metabolically-healthy very-high-LDL phenotypes such as LMHR.
Conflicts of interest
Several panel members disclose relationships with manufacturers of lipid-lowering drugs (consultancy, honoraria, research funding). Disclosures are listed in the source document.