ArticleThe New England journal of medicine2006
Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.
Article in The New England journal of medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 1,352 papers, 7 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Estudio clínico Fase III Para Evaluar la Eficacia terapéutica en Pacientes Mexicanos Con Dislipidemia Mediante el Uso vía Oral de L-Carnitina + Atorvastatina Comparado Con Atorvastatina
Evaluation of PCSK9 Enzyme in Non-Cholesterol Biological Pathways: In Vitro Demonstration of Direct Platelet-Related Effects of PCSK9 Enzyme
Muscle Characteristics Associated With Statin Therapy
A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Different Doses of ALN-PCSSC Given as Single or Multiple Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C
The Effect of Resistance Training on Proprotein Subtilisin Convertase Kexin 9 (PCSK-9) Level in Patients After Coronary Bypass Surgery
Who cites it
1,352 citing papers in PubMed, 7 syntheses or guidelines pooled it, 3,154 citations in OpenAlex.
- Sources of Heterogeneity in the Efficacy of Statins for Primary Prevention of Cardiovascular Diseases: A Systematic Review with Meta-Regression and Meta-Analysis of Within-Study Subgroup Differences.Cardiovascular drugs and therapy · 2026Pooled it
- Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.Genome biology · 2025Pooled it
- Prognostic value of lipid parameters among patients with heart failure: A systematic review and meta-analysis.ESC heart failure · 2025Pooled it
- Pooled it
- Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.Nature communications · 2025Pooled it
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- Efficacy and Safety of Evolocumab and Alirocumab as PCSK9 Inhibitors in Pediatric Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Trial
- Associations Between Gene Variants of Lipid-Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke.Journal of the American Heart Association · 2024Trial
- Effects of icosapent ethyl according to baseline residual risk in patients with atherosclerotic cardiovascular disease: results from REDUCE-IT.European heart journal. Cardiovascular pharmacotherapy · 2024Trial
- Effects of PCSK9 inhibitors on coronary atheroma morphology in patients with coronary artery disease treated with statins: a meta-analysis and systematic review.American journal of preventive cardiology · 2026Article
- Circulating PCSK9 as a sex-stratified predictor in primary prevention of cardiovascular disease: Insights from a prospective cohort study in Chinese adults.American journal of preventive cardiology · 2026Article
- Hypocholesterolemia in liver and cardiovascular disease: Friend or foe?Journal of internal medicine · 2026Review
- Population-Stratified Human Genetic Studies Are Not Eugenics: A Response to Donohue and Myles.Bioethics · 2026Article
- Betting on Biology: Rethinking Probability as the Currency of Risk in Biotechnology Portfolios.The AAPS journal · 2026Article
- Design of optimized epigenetic regulators for durable gene silencing with application to PCSK9 in nonhuman primates.Nature biotechnology · 2026Article
- Article
- Proteome-wide Mendelian randomization identifies APOM and TNXB as actionable mediators of steroid-sensitive nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- Putative protective role ofAtherosclerosis plus · 2026Article
- Article
1,292 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundA low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population.
methodsWe compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol.
resultsOf the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003).
conclusionsThese data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non-lipid-related cardiovascular risk factors.
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Registered trials
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.