High tierGuideline Or ConsensusCitation verified
Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel
Brian A Ference, Henry N Ginsberg, Ian Graham, Kausik K Ray, Chris J Packard, M John Chapman, Alberico L Catapano, EAS Consensus Panel - European Heart Journal, 2017
The European Atherosclerosis Society consensus panel appraised genetic, epidemiologic, and clinical evidence against formal criteria for causality and concluded that LDL causes ASCVD, citing a consistent dose-dependent, log-linear relationship between cumulative LDL exposure and risk.
Key findings
- The panel concludes the totality of evidence unequivocally establishes that LDL causes ASCVD.
- A remarkably consistent dose-dependent, log-linear association between cumulative LDL-C exposure and ASCVD risk, increasing with duration of exposure.
- Genetic variants raising or lowering LDL dose-dependently raise or lower ASCVD risk, concordant with randomized trial evidence.
Why this evidence tier (High)
- Risk of bias:
- Consensus synthesis by domain experts of high-quality study types (MR, RCTs, large cohorts); panel composition is mainstream lipidology.
- Precision:
- Extremely large pooled base (>2M participants, >150k events) gives high precision to the dose-response.
- Directness:
- Directly addresses the causal question using triangulated evidence types.
- Consistency:
- Emphasises consistency across genetic, epidemiologic, and trial evidence.
- Publication bias:
- A consensus statement curated by proponents; selection of supporting evidence is a consideration, though the underlying MR/RCT base is broad.
- Funding / COI:
- Panel members include authors with extensive pharmaceutical ties (disclosed in the source); a reason for caution, not downgrade by itself.
High certainty for the causal claim it makes; readers should note it is an advocacy-of-consensus document, and skeptics contest its framing.
- Population:
- Synthesis across separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials: more than 2 million participants, over 20 million person-years, and more than 150,000 cardiovascular events.
- Conflicts of interest:
- Multiple panel members report pharmaceutical industry relationships (consultancy/honoraria); see the full disclosure in the source.
- Funding:
- See source disclosures (European Atherosclerosis Society panel).
Limitations
- A consensus statement, not itself a primary experiment; reflects the mainstream interpretation.
- Does not specifically address metabolically-healthy very-high-LDL phenotypes (e.g. LMHR).