SynthesisCirculation2013

Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis.

S Matthijs Boekholdt, Benoit J Arsenault, G Kees Hovingh, Samia Mora, Terje R Pedersen, John C Larosa, K M A Welch, Pierre Amarenco, David A Demicco, Andrew M Tonkin and 11 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in Circulation, 2013. The graph read 4 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It also reports 3 associations that do not count as treatment evidence, such as HR 0.83 (0.81 to 0.86) for cardiovascular events. Cited by 89 papers, 5 of them syntheses that pooled it.

4numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 5 pooled it
19.8field-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

Cardiovascular eventsan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 0.830.81 to 0.86
HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82).
Cardiovascular eventsan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 0.790.72 to 0.82
HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82).
Lipidsan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 0.980.94 to 1.01
An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).
Lipidsan association or prognostic statement, not a treatment comparison · ascvd, dyslipidemiafeeds one cell of the map
HR 0.930.90 to 0.97
An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).

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.

Other lipid agents×cardiovascular events

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

10 readable studies in this cell: 5 favour the treatment, 5 find no difference, 0 favour the comparator.

Belief with this paper
0.80established · 4 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0020287818,144 enrolled · 2005
HR 0.940.89 to 0.99
NCT0061899526 enrolled · 2007
Geometric least-squares mean ratio 0.940.77 to 1.14

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

Other lipid agents×lipids

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

28 readable studies in this cell: 17 favour the treatment, 2 find no difference, 9 favour the comparator.

Belief with this paper
0.50contested · 17 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT004793881,216 enrolled · 2007
Δ -4.50-7.70 to -1.30
NCT00862251808 enrolled · 2009
Percent change in least-square means -14.8-19.6 to -9.91
NCT00485758796 enrolled · 2007
Δ -17.9-21.4 to -14.4
NCT00730132712 enrolled · 2008
Δ -5.75-9.43 to -2.07
NCT01763827615 enrolled · 2013
Δ -39.3-43.3 to -35.3
NCT01984424511 enrolled · 2013
Δ -37.8-42.3 to -33.3
NCT06005597407 enrolled · 2024
Least Squares (LS) Means -27.9-37.5 to -18.4
NCT03337308382 enrolled · 2017
Δ -38.0-46.5 to -29.6
NCT02227784366 enrolled · 2014
Δ -6.14-12.2 to -0.22
NCT01763905307 enrolled · 2013
Δ -38.1-43.7 to -33.0
NCT03001076269 enrolled · 2016
Δ -28.4-34.4 to -22.5

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

89 citing papers in PubMed, 5 syntheses or guidelines pooled it, 193 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Recent advances in precision nutrition and cardiometabolic diseases.Revista espanola de cardiologia (English ed.) · 2025
    Review

29 more citing papers are in PubMed but not listed here.

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

21 authors at 2 institutions in 2 countries.

S Matthijs BoekholdtDepartments of Cardiology (S.M.B.) and Vascular Medicine (B.J.A., G.K.H., J.J.P.K.), Academic Medical Center, Amsterdam, The Netherlands; Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (S.M., P.M.R.); Center of Preventive Medicine, Oslo University Hospital, Ulleval and University of Oslo, Norway (T.R.P.); State University of New York Health Science Center, Brooklyn, NY (J.C.L.); Rosalind Franklin University of Medicine and Science, North Chicago, IL (K.M.A.W.); Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France (P.A.); Global Pharmaceuticals Pfizer, New York, NY (D.A.D.); Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (A.M.T.); Department of Biochemistry and Lipid Clinic, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia (D.R.S.); NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia (A.K.); Medical Research Institute, University of Dundee, Dundee, United Kingdom (H.M.C.); Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (G.A.H.); Department of Medicine, Royal Free and University College Medical School, London, United Kingdom (D.J.B.); School of Biomedicine, University of Manchester, Manchester, United Kingdom (P.N.D.); Touro University, Mare Island, CA (M.B.C.); Department of Medicine, University of Texas Health Science Center, and VERDICT, South Texas Veterans Health Care System, San Antonio, TX (J.R.D.); and Weill Cornell Medical College, New York, NY (A.M.G.).
Benoit J Arsenault
G Kees Hovingh
Samia Mora
Terje R Pedersen
John C Larosa
K M A Welch
Pierre Amarenco
David A Demicco
Andrew M Tonkin
David R Sullivan
Adrienne Kirby
Helen M Colhoun
Graham A Hitman
D John Betteridge
Paul N Durrington
Michael B Clearfield
John R Downs
Antonio M Gotto
Paul M Ridker
John J P Kastelein
Australian Regenerative Medicine Institute · AUPfizer (United States) · US

Funding

NHLBI NIH HHS R01 HL117861NHLBI NIH HHS R01HL117861
8 · The paper itself

Abstract

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

backgroundIt is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. METHODS AND

resultsWe performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).

conclusionsAmong patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Indexed as

Angina, UnstableApolipoprotein A-ICardiovascular DiseasesCholesterol, HDLCholesterol, LDLClinical Trials as TopicFollow-Up StudiesHeart FailureHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMyocardial InfarctionPeripheral Arterial DiseaseProportional Hazards ModelsRisk FactorsRisk Reduction BehaviorStrokeApolipoprotein A-ICholesterol, HDLCholesterol, LDLHydroxymethylglutaryl-CoA Reductase InhibitorsTriglyceridesapolipoproteinscardiovascular diseaseshigh-density lipoprotein cholesterolmeta-analysis

Identifiers

PMID23965489
PMCPMC3807966
OpenAlexW2015450538

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.