Evidence map›Paper›PMID 32546049›Full record

SynthesisCirculation2020

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

Peter Willeit, Lena Tschiderer, Elias Allara, Kathrin Reuber, Lisa Seekircher, Lu Gao, Ximing Liao, Eva Lonn, Hertzel C Gerstein, Salim Yusuf and 67 more

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
267citing papers in PubMed, 15 pooled it
–field-weighted citation impact
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.

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

3 · Its place in the literature

Who cites it

267 citing papers in PubMed, 15 syntheses or guidelines pooled it.

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

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

77 authors.

Peter Willeit *Department of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Lena Tschiderer *Department of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Elias AllaraDepartment of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., E.A., M.J.S., S.G.T.).
Kathrin ReuberDepartment of Neurology, Goethe University, Frankfurt am Main, Germany (K.R., X.L., M. Sitzer., M.W.L.).
Lisa SeekircherDepartment of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Lu GaoMRC Biostatistics Unit, University of Cambridge, United Kingdom (L.G.).
Ximing LiaoDepartment of Neurology, Goethe University, Frankfurt am Main, Germany (K.R., X.L., M. Sitzer., M.W.L.).
Eva LonnDepartment of Medicine and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., H.C.G., S.Y.).
Hertzel C GersteinHamilton General Hospital, Ontario, Canada (E.L., H.C.G., S.Y.).
Salim YusufHamilton General Hospital, Ontario, Canada (E.L., H.C.G., S.Y.).
Frank P BrouwersDepartment of Cardiology, Haga Teaching Hospital, The Hague, The Netherlands (F.P.B.).
Folkert W AsselbergsDepartment of Cardiology (F.W.A.), University Medical Center Utrecht, The Netherlands.
Wiek van GilstDepartment of Experimental Cardiology, University Medical Center Groningen, The Netherlands (W.v.G.).
Sigmund A AnderssenDepartment of Sports Medicine, Norwegian School of Sports Sciences, Oslo, Norway (S.A.A.).
Diederick E GrobbeeJulius Center for Health Sciences and Primary Care (D.E.G., M.L.B.), University Medical Center Utrecht, The Netherlands.
John J P KasteleinDepartment of Vascular Medicine (J.J.P.K., E.S.), Academic Medical Centre, University of Amsterdam, The Netherlands.
Frank L J VisserenDepartment of Vascular Medicine (F.L.J.V.), University Medical Center Utrecht, The Netherlands.
George NtaiosDepartment of Medicine, University of Thessaly, Larissa, Greece (G.N.).
Apostolos I Hatzitolios1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Greece (A.I.H., C.S.).
Christos Savopoulos1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Greece (A.I.H., C.S.).
Pythia T NieuwkerkDepartment of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Erik StroesDepartment of Vascular Medicine (J.J.P.K., E.S.), Academic Medical Centre, University of Amsterdam, The Netherlands.
Matthew WaltersSchool of Medicine, Dentistry and Nursing (M.W.), University of Glasgow, United Kingdom.
Peter HigginsInstitute of Cardiovascular and Medical Sciences (P.H., J.D.), University of Glasgow, United Kingdom.
Jesse DawsonInstitute of Cardiovascular and Medical Sciences (P.H., J.D.), University of Glasgow, United Kingdom.
Paolo GreseleDivision of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy (P.G., G.G.).
Giuseppe GuglielminiDivision of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy (P.G., G.G.).
Rino MigliacciDivision of Internal Medicine, Cortona Hospital, Italy (R.M.).
Marat EzhovLaboratory of Lipid Disorders, National Medical Research Center of Cardiology, Moscow, Russia (M.E.), National Medical Research Center of Cardiology, Moscow, Russia.
Maya SafarovaAtherosclerosis Department (M. Safarova), National Medical Research Center of Cardiology, Moscow, Russia.
Tatyana BalakhonovaUltrasound Vascular Laboratory (T.B.), National Medical Research Center of Cardiology, Moscow, Russia.
Eiichi SatoDivision of Nephrology, Shinmatsudo Central General Hospital, Chiba, Japan (E.S., M.A., T.N.).
Mayuko AmahaDivision of Nephrology, Shinmatsudo Central General Hospital, Chiba, Japan (E.S., M.A., T.N.).
Tsukasa NakamuraDivision of Nephrology, Shinmatsudo Central General Hospital, Chiba, Japan (E.S., M.A., T.N.).
Kostas KapellasAustralian Research Centre for Population Oral Health, University of Adelaide, SA, Australia (K.K., L.M.J.).
Lisa M JamiesonAustralian Research Centre for Population Oral Health, University of Adelaide, SA, Australia (K.K., L.M.J.).
Michael SkiltonBoden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, NSW, Australia (M.Skilton).
James A BlumenthalDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, (J.A.B., A.S., P.J.S.).
Alan HinderliterDepartment of Medicine, University of North Carolina, Chapel Hill (A.H.).
Andrew SherwoodDepartment of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Patrick J SmithDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, (J.A.B., A.S., P.J.S.).
Michiel A van AgtmaelDepartment of Internal Medicine (M.A.v.A.) Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Peter ReissAmsterdam Institute for Global Health and Development, University of Amsterdam, The Netherlands (P.R.).
Marit G A van VonderenDepartment of Internal Medicine, Medical Center Leeuwarden, The Netherlands (M.G.A.v.V.).
Stefan KiechlVASCage GmbH, Research Centre on Vascular Ageing and Stroke, Innsbruck, Austria (S.K.).
Gerhard KlingenschmidDepartment of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
Matthias SitzerDepartment of Neurology, Klinikum Herford, Herford, Germany (M. Sitzer).
Coen D A StehouwerDepartment of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, The Netherlands (C.D.A.S.).
Heiko UthoffDepartment of Angiology, University Hospital Basel, Switzerland (H.U.).
Zhi-Yong ZouInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China (Z.-Y.Z.).
Ana R CunhaDepartment of Clinical Medicine, State University of Rio de Janeiro, Brazil (A.R.C., M.F.N.).
Mario F NevesDepartment of Clinical Medicine, State University of Rio de Janeiro, Brazil (A.R.C., M.F.N.).
Miles D WithamAGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle-upon-Tyne Hospitals Trust, United Kingdom (M.D.W.).
Hyun-Woong ParkDepartment of Internal Medicine, Gyeongsang National University Hospital, Daejeon, South Korea (H.-W.P., M.-S.L.).
Moo-Sik LeeDepartment of Preventive Medicine, Konyang University, Jinju, South Korea (M.-S.L.).
Jang-Ho BaeHeart Center, Konyang University Hospital, Daejeon, South Korea (J.-H.B.).
Enrique BernalInfectious Diseases Unit, Reina Sofia Hospital, Murcia, Spain (E.B.).
Kristian WachtellDepartment of Cardiology, Oslo University Hospital, Norway (K.W., S.E.K.).
Sverre E KjeldsenDepartment of Cardiology, Oslo University Hospital, Norway (K.W., S.E.K.).
Michael H OlsenDepartment of Internal Medicine, Holbaek Hospital, University of Southern Denmark, Odense (M.H.O.).
David PreissMRC Population Health Research Unit, Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom (D.P.).
Naveed SattarBHF Glasgow Cardiovascular Research Centre (N.S.), University of Glasgow, United Kingdom.
Edith BeishuizenInfectious Diseases Unit, Reina Sofia Hospital, Murcia, Spain (E.B.).
Menno V HuismanDepartment of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands (M.V.H.).
Mark A EspelandDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.).
Caroline SchmidtWallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden (C.S.).
Stefan AgewallOslo University Hospital Ullevål and Institute of Clinical Sciences, University of Oslo, Norway (S.A.).
Ercan OkNephrology Department, Ege University School of Medicine, Bornova-Izmir, Turkey (E.O, G.A.).
Gülay AşçiNephrology Department, Ege University School of Medicine, Bornova-Izmir, Turkey (E.O, G.A.).
Eric de GrootImagelabonline & Cardiovascular, Eindhoven and Lunteren, the Netherlands (E.d.G.).
Muriel P C GrootemanDepartment of Nephrology (M.P.C.G.), Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Peter J BlankestijnDepartment of Nephrology (P.J.B.), University Medical Center Utrecht, The Netherlands.
Michiel L BotsJulius Center for Health Sciences and Primary Care (D.E.G., M.L.B.), University Medical Center Utrecht, The Netherlands.
Michael J Sweeting *Department of Health Sciences, University of Leicester, United Kingdom (M.J.S.).
Simon G Thompson *Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., E.A., M.J.S., S.G.T.).
Matthias W Lorenz *Department of Neurology, Goethe University, Frankfurt am Main, Germany (K.R., X.L., M. Sitzer., M.W.L.).
PROG-IMT and the Proof-ATHERO Study Groups

Funding

Austrian Science Fund FWF P 32488
6 · The paper itself

Abstract

backgroundTo quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.

methodsWe systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach.

resultsWe analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients.

conclusionsThe extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Indexed as

Carotid Intima-Media ThicknessHeart Disease Risk FactorsCarotid Artery, CommonFemaleHumansMaleMiddle AgedMyocardial InfarctionRandomized Controlled Trials as TopicStrokecardiovascular diseasecarotid intima-media thicknessclinical trials as topicmeta-analysissurrogate marker

Identifiers

PMID32546049
PMCPMC7115957

What Socratic holds

Textmetadata
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.