Evidence mapPaperPMID 16554528Full record

ArticleThe New England journal of medicine2006

Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.

Jonathan C Cohen, Eric Boerwinkle, Thomas H Mosley, Helen H Hobbs

5 registry-linked trialsOpen access · bronzeAbstract readComparative Study
PubMed Publisher
In one paragraph

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 1,324 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,324citing papers in PubMed, 7 pooled it
93.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03696940 phase3unknown statusstarted 2018, after this paper: background citation

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

Ran2018Enrolled120Registered outcomes6Posted comparisons0ConditionsCardiovascular Risk Factor, DyslipidemiasArmsAtorvastatin 10mg, L-Carnitine 500Mg Oral Tablet + Atorvastatin 10 mg
Open the trial in the graph
NCT06675994 not yet recruitingstarted 2024, after this paper: background citation

Evaluation of PCSK9 Enzyme in Non-Cholesterol Biological Pathways: In Vitro Demonstration of Direct Platelet-Related Effects of PCSK9 Enzyme

Ran2024Enrolled80Registered outcomes4Posted comparisons0ConditionsDiabetes, Family History of Cerebrovascular Disease, Family History of Coronary Artery Disease, Family History of Peripheral Artery DiseaseArmsPCSK9 Antibody, PCSK9 Enzyme
Open the trial in the graph
NCT00990834 nawithdrawnnot on this mapstarted 2009, after this paper: background citation

Muscle Characteristics Associated With Statin Therapy

TypeinterventionalSponsorScripps HealthRan2009 to 2011Enrolled0ConditionsHydroxymethylglutaryl-CoA Reductase Inhibitors, MyopathyArmssimvastatin
NCT02597127 phase2completednot on this mapstarted 2016, after this paper: background citation

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

TypeinterventionalSponsorThe Medicines CompanyRan2016 to 2017Enrolled501ConditionsAtherosclerotic Cardiovascular Disease, Familial Hypercholesterolemia, DiabetesArmsALN-PCSSC, Normal Saline
NCT02674659 nacompletednot on this mapstarted 2016, after this paper: background citation

The Effect of Resistance Training on Proprotein Subtilisin Convertase Kexin 9 (PCSK-9) Level in Patients After Coronary Bypass Surgery

TypeinterventionalSponsorNational Cardiovascular Center Harapan Kita Hospital IndonesiaRan2016 to 2016Enrolled87ConditionsCoronary Artery DiseaseArmsresistance training, aerobic training
3 · Its place in the literature

Who cites it

1,324 citing papers in PubMed, 7 syntheses or guidelines pooled it, 3,154 citations in OpenAlex.

  1. Pooled it
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  17. Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026
    Review
  18. Article
  19. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  20. Review

1,264 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Jonathan C CohenDonald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Eric Boerwinkle
Thomas H Mosley
Helen H Hobbs
Cardiovascular Research Center · BRSouthwestern Medical Center · USThe University of Texas Health Science Center at Houston · US

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · 1985 to 2005
$28.1M
COMMUNITY AND COHORT SURVEILLANCE PROGRAMS-N01HC55015N01HC055015 · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · 1985 to 2005
$1.1M
COMMUNITY AND COHORT SURVEILLANCE PROGRAMN01HC055016 · BAYLOR COLLEGE OF MEDICINE · 1985 to 2000
$785k
FIELD CENTER FOR CCSPN01HC055019 · UNIVERSITY OF MINNESOTA TWIN CITIES · 1985 to 2000
$748k
FIELD CENTERN01HC055021 · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · 1985 to 2000
$617k
CCSP-FIELD CENTERN01HC055020 · JOHNS HOPKINS UNIVERSITY · 1985 to 2000
$334k
CENTRAL HEMOSTATIS LABORATORY FOR CCSPN01HC055022 · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 1985 to 2000
$264k
CCSP--FIELD CENTER AND ULTRASOUND READING CENTERN01HC055018 · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · 1985 to 2000
$104k
NHLBI NIH HHS HL 20948NHLBI NIH HHS N01-HC-55015NHLBI NIH HHS N01-HC-55016NHLBI NIH HHS N01-HC-55018NHLBI NIH HHS N01-HC-55019NHLBI NIH HHS N01-HC-55020NHLBI NIH HHS N01-HC-55021NHLBI NIH HHS N01-HC-55022
6 · The paper itself

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.

Indexed as

Codon, NonsenseGenetic VariationBlack or African AmericanBlack PeopleCarotid ArteriesCholesterol, LDLCohort StudiesCoronary DiseaseFemaleGene FrequencyGenotypeHumansHypolipoproteinemiasIncidenceMaleMiddle AgedCholesterol, LDLCodon, NonsensePCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesSerine Endopeptidases

Identifiers

PMID16554528
OpenAlexW2067539811

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.