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55/100

✓ Peer-reviewed alzhub usefulness score 55 out of 100. Treatments

Topic: Brain proteins, microglia and lab models

Importance The balance between the potential long-term clinical benefits and harms associated with genetic cholesteryl ester transfer protein (CETP) deficiency, mimicking pharmacologic CETP inhibition, is unknown. Objective To assess the relative benefits and harms associated with genetic CETP deficiency. The study first tested whether a CETP allele score was associated with morbidity and mortality, when scaled to genetically lower levels of non-high-density lipoprotein (HDL) cholesterol (ie, 17 mg/dL), corresponding to the reduction observed for anacetrapib vs placebo in the Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial. Second, the study assessed how much of the change in morbidity and mortality was associated with genetically lower levels of non-HDL cholesterol. Finally, the balance between the potential long-term clinical benefits and harms associated with genetic CETP deficiency was quantified. For AMD, the analyses also included higher levels of HDL cholesterol associated with genetic CETP deficiency. Results Of 102 607 individuals in the study, 56 559 (55%) were women (median age, 58 years [IQR, 47-67 years]). Multivariable adjusted hazard ratios showed that a genetically lower level of non-HDL cholesterol (ie, 17 mg/dL) was associated with a lower risk of cardiovascular mortality (hazard ratio [HR], 0.77 [95% CI, 0.62-0.95]), ischemic heart disease (HR, 0.80 [95% CI, 0.68-0.95]), myocardial infarction (HR, 0.72 [95% CI, 0.55-0.93]), peripheral arterial disease (HR, 0.80 [95% CI, 0.63-1.02]), and vascular dementia (HR, 0.38 [95% CI, 0.18-0.80]) and an increased risk of AMD (HR, 2.33 [95% CI, 1.63-3.30]) but was not associated with all-cause mortality (HR, 0.91 [95% CI, 0.81-1.02]), ischemic stroke (HR, 1.05 [95% CI, 0.81-1.36]), or Alzheimer disease (HR, 1.25 [95% CI, 0.89-1.76]). When scaled to a higher level of HDL cholesterol, the increased risk of AMD was even larger. A considerable fraction of the lower risk of cardiovascular end points was associated with genetically lower levels of non-HDL cholesterol, while the higher risk of AMD was associated with genetically higher levels of HDL cholesterol. Per 1 million person-years, the projected 1916 more AMD events associated with genetically higher levels of HDL cholesterol was similar to the 1962 fewer events of cardiovascular mortality and myocardial infarction combined associated with genetically lower levels of non-HDL cholesterol. Conclusions and

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Nordestgaard, L. T., Christoffersen, M., Lauridsen, B. K., Afzal, S., Nordestgaard, B. G., Frikke-Schmidt, R., et al. (2022). Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population. JAMA cardiology. https://doi.org/10.1001/jamacardio.2021.3728

Vancouver

Nordestgaard LT, Christoffersen M, Lauridsen BK, Afzal S, Nordestgaard BG, Frikke-Schmidt R, et al. Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population. JAMA cardiology. 2022. doi:10.1001/jamacardio.2021.3728. PMID: 34613338.

BibTeX

@article{nordestgaard2022-34613338,
  author  = {Nordestgaard, L. T. and Christoffersen, M. and Lauridsen, B. K. and Afzal, S. and Nordestgaard, B. G. and Frikke-Schmidt, R. and Tybjærg-Hansen, A.},
  title   = {{Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population}},
  journal = {JAMA cardiology},
  year    = {2022},
  doi     = {10.1001/jamacardio.2021.3728},
  pmid    = {34613338},
  url     = {https://doi.org/10.1001/jamacardio.2021.3728}
}

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Key findings

Importance The balance between the potential long-term clinical benefits and harms associated with genetic cholesteryl ester transfer protein (CETP) deficiency, mimicking pharmacologic CETP inhibition, is unknown.
Objective To assess the relative benefits and harms associated with genetic CETP deficiency.
The study first tested whether a CETP allele score was associated with morbidity and mortality, when scaled to genetically lower levels of non-high-density lipoprotein (HDL) cholesterol (ie, 17 mg/dL), corresponding to the reduction observed for anacetrapib vs placebo in the Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial.
Second, the study assessed how much of the change in morbidity and mortality was associated with genetically lower levels of non-HDL cholesterol.
Finally, the balance between the potential long-term clinical benefits and harms associated with genetic CETP deficiency was quantified.

Why it matters

This study examined genetic cholesteryl ester transfer protein deficiency and its balance of long-term benefits and harms, including a genetically lower level of non-HDL cholesterol associated with lower cardiovascular mortality. It is about cholesterol genetics and cardiovascular outcomes, not about treating, curing, or preventing Alzheimer's disease.

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Study details

Participants607
Evidence strengthHigh

How this study scored 55/100

Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (JAMA cardiology)
Journal's citation record	2 / 4	JAMA Cardiology: journal h-index 169 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	5 / 5	Rated “high” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	3 / 5	2022 — within 6 year(s) of the newest study here
Sample size	2 / 4	607 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 61 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	10.2 citations a year over 6 year(s) since 2022
Impact for its field and year	4 / 6	Cited 9.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	2 / 4	Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Anne Tybjærg‐Hansen: h-index 115 (OpenAlex, whole career)
Institution's track record	1 / 3	University of Copenhagen: institution h-index 1,378 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 7 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 34613338)
Free to read	0 / 2	Behind a paywall — scores zero
Total	55 / 100	—

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