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.
Level 5 - mechanism / opinion, no new human data
Expert consensus statement and narrative synthesis of existing meta-analyses, trials, and genetic studies
PubMed 28444290 · doi:10.1093/eurheartj/ehx144
What was done
The European Atherosclerosis Society Consensus Panel evaluated the clinical and genetic evidence establishing causality between low-density lipoproteins (LDLs) and atherosclerotic cardiovascular disease (ASCVD). They synthesized evidence across rare genetic mutations, Mendelian randomization studies, prospective epidemiological cohorts, and randomized controlled trials of LDL-lowering interventions.
What was found
Rare mutations affecting LDL receptor function showed dose-dependent increases or decreases in ASCVD risk concordant with LDL cholesterol (LDL-C) levels. Meta-analyses across more than 200 prospective cohort studies, Mendelian randomization studies, and randomized trials (encompassing >2 million participants, >20 million person-years of follow-up, and >150,000 cardiovascular events) demonstrated a consistent, dose-dependent, log-linear relationship between absolute magnitude and duration of LDL-C exposure and ASCVD risk. Risk reduction from LDL lowering was proportional to absolute LDL-C reduction and duration of exposure across all mechanisms, provided particle reduction was concordant without off-target effects.
Why it matters
This consensus clarifies that LDL is a direct causal driver of atherosclerosis rather than merely a correlated biomarker, reinforcing the clinical rationale for lowering LDL-C to prevent cardiovascular events.
Limits
The abstract does not provide specific numerical effect sizes, odds ratios, or confidence intervals. As an expert consensus statement and narrative synthesis, it aggregates existing studies rather than executing a novel, preregistered systematic review protocol.
Cited by
- supports Mendelian randomization studies demonstrate a direct linear relationship between lifetime exposure to LDL cholesterol and the risk of heart disease.