Trial reportCirculation2015

High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy.

Brendan M Everett, Tanja Zeller, Robert J Glynn, Paul M Ridker, Stefan Blankenberg

Registry-linked trialOpen access · hybridAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Circulation, 2015. The graph read 2 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports 2 associations that do not count as treatment evidence, such as HR 1.45 (1.03 to 2.04) for all-cause mortality. It is linked to trial NCT00239681 (A Randomized, Double-Blind, Placebo Controlled, Multicenter, Phase 3 Study of Rosuvastatin), which is not on this map. Cited by 59 papers, 3 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 3 pooled it
14.3field-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.

Read, but not usablea number the graph found but could not read as for or against

All-cause mortalityhighest tertile of BNP vs lowest tertile of BNPan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 1.451.03 to 2.04
The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02).
All-cause mortalityhighest tertile of hsTnI vs lowest tertile of hsTnIan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 2.611.81 to 3.78
The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Statins×all-cause mortality

No readable resultOpen on the map →What to test next →

14 readable studies in this cell: 3 favour the treatment, 9 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT023442907,769 enrolled · 2015
HR 0.880.70 to 1.12
HR 1.010.91 to 1.11
NCT03944512102 enrolled · 2019
RR 0.670.37 to 1.19
RR 0.990.89 to 1.11

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

NCT00239681 phase3terminatednot on this map

A Randomized, Double-Blind, Placebo Controlled, Multicenter, Phase 3 Study of Rosuvastatin (CRESTOR®) 20 mg in the Prevention of Cardiovascular Events Among Subjects With Low Levels of Low Density Lipoprotein(LDL) Cholesterol & Elevated Levels of C-Reactive Protein

TypeinterventionalSponsorAstraZenecaRan2003 to 2008Enrolled17,802ConditionsElevated High-sensitivity C-Reactive Protein (hsCRP)ArmsRosuvastatin, Placebo
5 · Its place in the literature

Who cites it

59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 127 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Brendan M EverettFrom Divisions of Cardiovascular (B.M.E., P.M.R.) and Preventive Medicine (B.M.E., R.J.G., P.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Germany (T.Z., S.B.); and German Centre for Cardiovascular Research Partner Site Hamburg/Lübeck/Kiel, Germany (T.Z., S.B.). beverett@partners.org.
Tanja ZellerFrom Divisions of Cardiovascular (B.M.E., P.M.R.) and Preventive Medicine (B.M.E., R.J.G., P.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Germany (T.Z., S.B.); and German Centre for Cardiovascular Research Partner Site Hamburg/Lübeck/Kiel, Germany (T.Z., S.B.).
Robert J GlynnFrom Divisions of Cardiovascular (B.M.E., P.M.R.) and Preventive Medicine (B.M.E., R.J.G., P.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Germany (T.Z., S.B.); and German Centre for Cardiovascular Research Partner Site Hamburg/Lübeck/Kiel, Germany (T.Z., S.B.).
Paul M RidkerFrom Divisions of Cardiovascular (B.M.E., P.M.R.) and Preventive Medicine (B.M.E., R.J.G., P.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Germany (T.Z., S.B.); and German Centre for Cardiovascular Research Partner Site Hamburg/Lübeck/Kiel, Germany (T.Z., S.B.).
Stefan BlankenbergFrom Divisions of Cardiovascular (B.M.E., P.M.R.) and Preventive Medicine (B.M.E., R.J.G., P.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University Heart Centre Hamburg, Clinic for General and Interventional Cardiology, Germany (T.Z., S.B.); and German Centre for Cardiovascular Research Partner Site Hamburg/Lübeck/Kiel, Germany (T.Z., S.B.).
Universität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundCardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood. METHODS AND

resultsWe measured high-sensitivity cardiac troponin I (hsTnI) in 12 956 and BNP in 11 076 participants without cardiovascular disease in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial before randomization to rosuvastatin 20 mg/d or placebo. Nearly 92% of participants had detectable circulating hsTnI, and 2.9% of men and 4.1% of women had levels above proposed sex-specific reference limits of 36 and 15 ng/L, respectively. hsTnI concentrations in the highest tertile were associated with a first major cardiovascular event (adjusted hazard ratio [aHR], 2.19; 95% confidence interval, 1.56-3.06; P for trend <0.001). BNP levels in the highest tertile were also associated a first cardiovascular event (aHR, 1.94; 95% confidence interval, 1.41-2.68; P for trend <0.001). The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02). Rosuvastatin was equally effective in preventing a first cardiovascular event across categories of hsTnI (aHR range, 0.50-0.60) and BNP (aHR range, 0.42-0.67) with no statistically significant evidence of interaction (P for interaction=0.53 and 0.20, respectively).

conclusionsIn a contemporary primary prevention population, baseline cardiac troponin I and BNP were associated with the risk of vascular events and all-cause mortality. The benefits of rosuvastatin were substantial and consistent regardless of baseline hsTnI or BNP concentrations. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Indexed as

AgedAngina, UnstableBiomarkersCholesterol, HDLComorbidityCoronary DiseaseDouble-Blind MethodFemaleFluorobenzenesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypertensionIncidenceMaleMiddle AgedNatriuretic Peptide, BrainBiomarkersCholesterol, HDLFluorobenzenesHydroxymethylglutaryl-CoA Reductase InhibitorsNatriuretic Peptide, BrainPyrimidinesRosuvastatin CalciumSulfonamidesTNNT3 protein, humanTroponin Thydroxymethylglutaryl-CoA reductase inhibitorsnatriuretic peptide, brainprimary preventiontroponin

Identifiers

PMID25825410
PMCPMC4444427
OpenAlexW2075952435

What Socratic holds

Texttitle and abstract
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.