Systematic reviewindependent cross-checkabstract checked I-FAT-109 standard review
In older people, higher LDL was not linked to earlier death in cohort studies
Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.
Overview
Ravnskov U et al.. BMJ Open 2016 · PMID 27292972 · DOI 10.1136/bmjopen-2015-010401
Inverse association in 16 of 28 cohorts.
Does the study support the specific claim? Partly · Methodological quality: low
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Check LDL and death in the elderly.
- How was the study done?
Systematic review, vote counting.
- How many people, animals or samples were studied?
68,094 people.
- What was actually found?
Higher LDL not linked to more deaths.
- How large was the observed effect?
No pooled estimate.
- What do the results mean in everyday life?
Low cholesterol in old age often reflects illness.
- What are the study's limitations?
Reverse causation; weak methods.
- What does it say about Elawady's specific claim?
Weak support for the claim.
- Do the results apply to Germany and Europe?
n/a
- What can explicitly not be concluded from this study?
Cannot show LDL is harmless.
Scientific in-depth review
1. Full reference
- Authors
- Ravnskov U et al.
- Journal
- BMJ Open
- Year
- 2016
- Identifier
- PMID 27292972 DOI 10.1136/bmjopen-2015-010401
- Verification
- verified – PubMed efetch 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Is LDL-C associated with mortality in people >=60 y?
3. Study design and population
- Study design
- Systematic review – Systematic review of cohort studies (PubMed only), no meta-analysis
- Population
Elderly in general-population cohorts
- Country
Multinational
- Period
to 2015
- Sample size
19 studies, 30 cohorts, 68,094 people
- Inclusion and exclusion criteria
Cohorts reporting LDL-C and mortality in >=60 y
4. Methods and endpoints
- Exposure / intervention
LDL-C
- Comparator
Lower LDL-C
- Endpoints
All-cause and CV mortality
- Statistical methods
Vote counting
5. Actual results
- Results
Inverse association between LDL-C and all-cause mortality in 16 cohorts (14 significant; 92% of participants); none in the rest; CV mortality highest in lowest LDL-C quartile in 2 cohorts, no association in 7.
- Absolute risks
not reported
- Authors' conclusion
High LDL-C is inversely associated with mortality in most people over 60; this questions the cholesterol hypothesis.
6. Strengths
- Addresses older adults
7. Weaknesses
- Single database
- Vote counting
- Reverse causation (illness and frailty lower cholesterol)
- Mortality, not atherosclerosis
- Contradicted by randomised evidence in older people
8. Risk of bias
- Orienting tool
- ROBIS
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- high
- Rationale
Reverse causation not addressed; selective framework.
9. Assessment of the statistical interpretation
Observational associations in the elderly are confounded by frailty; cannot test causality.
10. Relevance to the specific claim
The most-cited published support for 'cholesterol is not the enemy'; weak because of reverse causation and contradicted by RCTs of LDL lowering in older people (I-FAT-110).
11. Independent contrary findings
I-FAT-110 (CTT older people), I-FAT-02, I-INTB-18.
12. Transferability to Germany and Europe
n/a
13. Overall methodological judgement
Very low certainty; does not overturn causal evidence.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | low |
| Risk of bias | high |
| Precision of results | not applicable |
| Directness | indirect |
| Reproducibility | unknown |
| Consistency with the overall evidence | inconsistent |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
n/a