SynthesisPharmacogenetics and genomics2013
Robust association of the LPA locus with low-density lipoprotein cholesterol lowering response to statin treatment in a meta-analysis of 30 467 individuals from both randomized control trials and observational studies and association with coronary artery disease outcome during statin treatment.
Synthesis in Pharmacogenetics and genomics, 2013. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It is linked to trial NCT02783469 (Genetics of Diabetes Audit and Research in Tayside Scotland), which is not on this map. Cited by 10 papers, 2 of them syntheses that pooled it.
What it found
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RESULTS: We replicated the findings of the RCTs, with the G allele of rs10455872 being associated with a 0.10 mmol/l per allele poorer reduction in LDLc in response to statin treatment, and conducted a meta-analysis with previously published RCTs (P = 1.46 × 10, n = 30 467).
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Investigational compounds×lipids
No readable resultOpen on the map →What to test next →9 readable studies in this cell: 4 favour the treatment, 3 find no difference, 2 favour the comparator.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetics of Diabetes Audit and Research in Tayside Scotland (DOLORisk Dundee)
Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.Circulation · 2018 · on this mapPooled it
- Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.Journal of medical genetics · 2016Pooled it
- Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics.Cardiovascular research · 2022Review
- Genomic Influence in the Prevention of Cardiovascular Diseases with a Sterol-Based Treatment.Diseases (Basel, Switzerland) · 2018Article
- Cohort Profile: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS).International journal of epidemiology · 2018Article
- Involvement of inflammatory responses in the early development of calcific aortic valve disease: lessons from statin therapy.Animal cells and systems · 2018Review
- Lipoprotein(a) and oxidized phospholipids in calcific aortic valve stenosis.Current opinion in cardiology · 2016Review
- The genetics of drug efficacy: opportunities and challenges.Nature reviews. Genetics · 2016Review
- Phenotype standardization for statin-induced myotoxicity.Clinical pharmacology and therapeutics · 2014Article
- Modulation of plasma triglycerides concentration by sterol-based treatment in children carrying different genes.Annals of pediatric cardiologyArticle
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
objectivesThe LPA single-nucleotide polymorphism rs10455872 has been associated with low-density lipoprotein cholesterol (LDLc) lowering response to statins in several randomized control trials (RCTs) and is a known coronary artery disease (CAD) marker. However, it is unclear what residual risk of CAD this marker may have during statin treatment.
methodsUsing electronic medical records linked to the GoDARTS genotyped population, we identified over 8000 patients on statins in Tayside, Scotland.
resultsWe replicated the findings of the RCTs, with the G allele of rs10455872 being associated with a 0.10 mmol/l per allele poorer reduction in LDLc in response to statin treatment, and conducted a meta-analysis with previously published RCTs (P = 1.46 × 10, n = 30 467). We showed an association between rs10455872 and CAD in statin-treated individuals and have replicated this finding in the Utrecht Cardiovascular Pharmacogenetics study (combined odds ratio 1.41, 95% confidence interval 1.17-1.68, P = 4.5 × 10, n = 8822) suggesting that statin treatment does not abrogate this well-established genetic risk for CAD. Furthermore, in a Cox proportional hazards model with LDLc measured time dependently, we demonstrated that the relationship between CAD and rs10455872 was independent of LDLc during statin treatment.
conclusionIndividuals with the G allele of rs10455872, which represents approximately one in seven patients, have a higher risk of CAD than the majority of the population even after treatment with statins; and therefore represent a vulnerable group requiring an alternative medication in addition to statin treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.