Meta-Analysis

. 2020 Aug 18;142(7):621-642.

doi: 10.1161/CIRCULATIONAHA.120.046361. Epub 2020 Jun 17.

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

Peter Willeit^#¹, Lena Tschiderer^#¹, Elias Allara², Kathrin Reuber³, Lisa Seekircher¹, Lu Gao⁴, Ximing Liao³, Eva Lonn⁵, Hertzel C Gerstein⁶, Salim Yusuf⁶, Frank P Brouwers⁷, Folkert W Asselbergs⁸, Wiek van Gilst⁹, Sigmund A Anderssen¹⁰, Diederick E Grobbee¹¹, John J P Kastelein¹², Frank L J Visseren¹³, George Ntaios¹⁴, Apostolos I Hatzitolios¹⁵, Christos Savopoulos¹⁵, Pythia T Nieuwkerk¹, Erik Stroes¹², Matthew Walters¹⁶, Peter Higgins¹⁷, Jesse Dawson¹⁷, Paolo Gresele¹⁸, Giuseppe Guglielmini¹⁸, Rino Migliacci¹⁹, Marat Ezhov²⁰, Maya Safarova²¹, Tatyana Balakhonova²², Eiichi Sato²³, Mayuko Amaha²³, Tsukasa Nakamura²³, Kostas Kapellas²⁴, Lisa M Jamieson²⁴, Michael Skilton²⁵, James A Blumenthal²⁶, Alan Hinderliter²⁷, Andrew Sherwood¹, Patrick J Smith²⁶, Michiel A van Agtmael²⁸, Peter Reiss²⁹, Marit G A van Vonderen³⁰, Stefan Kiechl³¹, Gerhard Klingenschmid¹, Matthias Sitzer³², Coen D A Stehouwer³³, Heiko Uthoff³⁴, Zhi-Yong Zou³⁵, Ana R Cunha³⁶, Mario F Neves³⁶, Miles D Witham³⁷, Hyun-Woong Park³⁸, Moo-Sik Lee³⁹, Jang-Ho Bae⁴⁰, Enrique Bernal⁴¹, Kristian Wachtell⁴², Sverre E Kjeldsen⁴², Michael H Olsen⁴³, David Preiss⁴⁴, Naveed Sattar⁴⁵, Edith Beishuizen⁴¹, Menno V Huisman⁴⁶, Mark A Espeland⁴⁷, Caroline Schmidt⁴⁸, Stefan Agewall⁴⁹, Ercan Ok⁵⁰, Gülay Aşçi⁵⁰, Eric de Groot⁵¹, Muriel P C Grooteman⁵², Peter J Blankestijn⁵³, Michiel L Bots¹¹, Michael J Sweeting^#⁵⁴, Simon G Thompson^#², Matthias W Lorenz^#³; PROG-IMT and the Proof-ATHERO Study Groups

Affiliations

¹ Department of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
² Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., E.A., M.J.S., S.G.T.).
³ Department of Neurology, Goethe University, Frankfurt am Main, Germany (K.R., X.L., M. Sitzer., M.W.L.).
⁴ MRC Biostatistics Unit, University of Cambridge, United Kingdom (L.G.).
⁵ Department of Medicine and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., H.C.G., S.Y.).
⁶ Hamilton General Hospital, Ontario, Canada (E.L., H.C.G., S.Y.).
⁷ Department of Cardiology, Haga Teaching Hospital, The Hague, The Netherlands (F.P.B.).
⁸ Department of Cardiology (F.W.A.), University Medical Center Utrecht, The Netherlands.
⁹ Department of Experimental Cardiology, University Medical Center Groningen, The Netherlands (W.v.G.).
¹⁰ Department of Sports Medicine, Norwegian School of Sports Sciences, Oslo, Norway (S.A.A.).
¹¹ Julius Center for Health Sciences and Primary Care (D.E.G., M.L.B.), University Medical Center Utrecht, The Netherlands.
¹² Department of Vascular Medicine (J.J.P.K., E.S.), Academic Medical Centre, University of Amsterdam, The Netherlands.
¹³ Department of Vascular Medicine (F.L.J.V.), University Medical Center Utrecht, The Netherlands.
¹⁴ Department of Medicine, University of Thessaly, Larissa, Greece (G.N.).
¹⁵ 1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Greece (A.I.H., C.S.).
¹⁶ School of Medicine, Dentistry and Nursing (M.W.), University of Glasgow, United Kingdom.
¹⁷ Institute of Cardiovascular and Medical Sciences (P.H., J.D.), University of Glasgow, United Kingdom.
¹⁸ Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy (P.G., G.G.).
¹⁹ Division of Internal Medicine, Cortona Hospital, Italy (R.M.).
²⁰ Laboratory of Lipid Disorders, National Medical Research Center of Cardiology, Moscow, Russia (M.E.), National Medical Research Center of Cardiology, Moscow, Russia.
²¹ Atherosclerosis Department (M. Safarova), National Medical Research Center of Cardiology, Moscow, Russia.
²² Ultrasound Vascular Laboratory (T.B.), National Medical Research Center of Cardiology, Moscow, Russia.
²³ Division of Nephrology, Shinmatsudo Central General Hospital, Chiba, Japan (E.S., M.A., T.N.).
²⁴ Australian Research Centre for Population Oral Health, University of Adelaide, SA, Australia (K.K., L.M.J.).
²⁵ Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, NSW, Australia (M.Skilton).
²⁶ Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, (J.A.B., A.S., P.J.S.).
²⁷ Department of Medicine, University of North Carolina, Chapel Hill (A.H.).
²⁸ Department of Internal Medicine (M.A.v.A.) Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
²⁹ Amsterdam Institute for Global Health and Development, University of Amsterdam, The Netherlands (P.R.).
³⁰ Department of Internal Medicine, Medical Center Leeuwarden, The Netherlands (M.G.A.v.V.).
³¹ VASCage GmbH, Research Centre on Vascular Ageing and Stroke, Innsbruck, Austria (S.K.).
³² Department of Neurology, Klinikum Herford, Herford, Germany (M. Sitzer).
³³ Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, The Netherlands (C.D.A.S.).
³⁴ Department of Angiology, University Hospital Basel, Switzerland (H.U.).
³⁵ Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China (Z.-Y.Z.).
³⁶ Department of Clinical Medicine, State University of Rio de Janeiro, Brazil (A.R.C., M.F.N.).
³⁷ AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle-upon-Tyne Hospitals Trust, United Kingdom (M.D.W.).
³⁸ Department of Internal Medicine, Gyeongsang National University Hospital, Daejeon, South Korea (H.-W.P., M.-S.L.).
³⁹ Department of Preventive Medicine, Konyang University, Jinju, South Korea (M.-S.L.).
⁴⁰ Heart Center, Konyang University Hospital, Daejeon, South Korea (J.-H.B.).
⁴¹ Infectious Diseases Unit, Reina Sofia Hospital, Murcia, Spain (E.B.).
⁴² Department of Cardiology, Oslo University Hospital, Norway (K.W., S.E.K.).
⁴³ Department of Internal Medicine, Holbaek Hospital, University of Southern Denmark, Odense (M.H.O.).
⁴⁴ MRC Population Health Research Unit, Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom (D.P.).
⁴⁵ BHF Glasgow Cardiovascular Research Centre (N.S.), University of Glasgow, United Kingdom.
⁴⁶ Department of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands (M.V.H.).
⁴⁷ Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.).
⁴⁸ Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden (C.S.).
⁴⁹ Oslo University Hospital Ullevål and Institute of Clinical Sciences, University of Oslo, Norway (S.A.).
⁵⁰ Nephrology Department, Ege University School of Medicine, Bornova-Izmir, Turkey (E.O, G.A.).
⁵¹ Imagelabonline & Cardiovascular, Eindhoven and Lunteren, the Netherlands (E.d.G.).
⁵² Department of Nephrology (M.P.C.G.), Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
⁵³ Department of Nephrology (P.J.B.), University Medical Center Utrecht, The Netherlands.
⁵⁴ Department of Health Sciences, University of Leicester, United Kingdom (M.J.S.).

^# Contributed equally.

PMID: 32546049
PMCID: PMC7115957
DOI: 10.1161/CIRCULATIONAHA.120.046361

Meta-Analysis

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

Peter Willeit et al. Circulation. 2020.

. 2020 Aug 18;142(7):621-642.

doi: 10.1161/CIRCULATIONAHA.120.046361. Epub 2020 Jun 17.

Authors

Affiliations

¹ Department of Neurology, Medical University of Innsbruck, Austria (P.W., L.T., L.S., S.K., G.K.).
² Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., E.A., M.J.S., S.G.T.).
³ Department of Neurology, Goethe University, Frankfurt am Main, Germany (K.R., X.L., M. Sitzer., M.W.L.).
⁴ MRC Biostatistics Unit, University of Cambridge, United Kingdom (L.G.).
⁵ Department of Medicine and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (E.L., H.C.G., S.Y.).
⁶ Hamilton General Hospital, Ontario, Canada (E.L., H.C.G., S.Y.).
⁷ Department of Cardiology, Haga Teaching Hospital, The Hague, The Netherlands (F.P.B.).
⁸ Department of Cardiology (F.W.A.), University Medical Center Utrecht, The Netherlands.
⁹ Department of Experimental Cardiology, University Medical Center Groningen, The Netherlands (W.v.G.).
¹⁰ Department of Sports Medicine, Norwegian School of Sports Sciences, Oslo, Norway (S.A.A.).
¹¹ Julius Center for Health Sciences and Primary Care (D.E.G., M.L.B.), University Medical Center Utrecht, The Netherlands.
¹² Department of Vascular Medicine (J.J.P.K., E.S.), Academic Medical Centre, University of Amsterdam, The Netherlands.
¹³ Department of Vascular Medicine (F.L.J.V.), University Medical Center Utrecht, The Netherlands.
¹⁴ Department of Medicine, University of Thessaly, Larissa, Greece (G.N.).
¹⁵ 1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Greece (A.I.H., C.S.).
¹⁶ School of Medicine, Dentistry and Nursing (M.W.), University of Glasgow, United Kingdom.
¹⁷ Institute of Cardiovascular and Medical Sciences (P.H., J.D.), University of Glasgow, United Kingdom.
¹⁸ Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy (P.G., G.G.).
¹⁹ Division of Internal Medicine, Cortona Hospital, Italy (R.M.).
²⁰ Laboratory of Lipid Disorders, National Medical Research Center of Cardiology, Moscow, Russia (M.E.), National Medical Research Center of Cardiology, Moscow, Russia.
²¹ Atherosclerosis Department (M. Safarova), National Medical Research Center of Cardiology, Moscow, Russia.
²² Ultrasound Vascular Laboratory (T.B.), National Medical Research Center of Cardiology, Moscow, Russia.
²³ Division of Nephrology, Shinmatsudo Central General Hospital, Chiba, Japan (E.S., M.A., T.N.).
²⁴ Australian Research Centre for Population Oral Health, University of Adelaide, SA, Australia (K.K., L.M.J.).
²⁵ Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, NSW, Australia (M.Skilton).
²⁶ Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, (J.A.B., A.S., P.J.S.).
²⁷ Department of Medicine, University of North Carolina, Chapel Hill (A.H.).
²⁸ Department of Internal Medicine (M.A.v.A.) Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
²⁹ Amsterdam Institute for Global Health and Development, University of Amsterdam, The Netherlands (P.R.).
³⁰ Department of Internal Medicine, Medical Center Leeuwarden, The Netherlands (M.G.A.v.V.).
³¹ VASCage GmbH, Research Centre on Vascular Ageing and Stroke, Innsbruck, Austria (S.K.).
³² Department of Neurology, Klinikum Herford, Herford, Germany (M. Sitzer).
³³ Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, The Netherlands (C.D.A.S.).
³⁴ Department of Angiology, University Hospital Basel, Switzerland (H.U.).
³⁵ Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China (Z.-Y.Z.).
³⁶ Department of Clinical Medicine, State University of Rio de Janeiro, Brazil (A.R.C., M.F.N.).
³⁷ AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle-upon-Tyne Hospitals Trust, United Kingdom (M.D.W.).
³⁸ Department of Internal Medicine, Gyeongsang National University Hospital, Daejeon, South Korea (H.-W.P., M.-S.L.).
³⁹ Department of Preventive Medicine, Konyang University, Jinju, South Korea (M.-S.L.).
⁴⁰ Heart Center, Konyang University Hospital, Daejeon, South Korea (J.-H.B.).
⁴¹ Infectious Diseases Unit, Reina Sofia Hospital, Murcia, Spain (E.B.).
⁴² Department of Cardiology, Oslo University Hospital, Norway (K.W., S.E.K.).
⁴³ Department of Internal Medicine, Holbaek Hospital, University of Southern Denmark, Odense (M.H.O.).
⁴⁴ MRC Population Health Research Unit, Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom (D.P.).
⁴⁵ BHF Glasgow Cardiovascular Research Centre (N.S.), University of Glasgow, United Kingdom.
⁴⁶ Department of Thrombosis and Hemostasis, Leiden University Medical Center, The Netherlands (M.V.H.).
⁴⁷ Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (M.A.E.).
⁴⁸ Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden (C.S.).
⁴⁹ Oslo University Hospital Ullevål and Institute of Clinical Sciences, University of Oslo, Norway (S.A.).
⁵⁰ Nephrology Department, Ege University School of Medicine, Bornova-Izmir, Turkey (E.O, G.A.).
⁵¹ Imagelabonline & Cardiovascular, Eindhoven and Lunteren, the Netherlands (E.d.G.).
⁵² Department of Nephrology (M.P.C.G.), Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
⁵³ Department of Nephrology (P.J.B.), University Medical Center Utrecht, The Netherlands.
⁵⁴ Department of Health Sciences, University of Leicester, United Kingdom (M.J.S.).

^# Contributed equally.

PMID: 32546049
PMCID: PMC7115957
DOI: 10.1161/CIRCULATIONAHA.120.046361

Abstract

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

Methods: We 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.

Results: We 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.

Conclusions: The 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.

Keywords: cardiovascular disease; carotid intima-media thickness; clinical trials as topic; meta-analysis; surrogate marker.

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Conflict of interest statement

Conflict of Interest Disclosures

P. Willeit reports grants from the German Research Foundation DFG, the Austrian Science Fund FWF, the Austrian Research Promotion Agency FFG and the Dr.-Johannes-and-Hertha-Tuba Foundation during the conduct of the study. L. Tschiderer reports grants from the Dr.-Johannes-and-Hertha-Tuba Foundation during the conduct of the study and non-financial support from Sanofi outside the submitted work. E. Allara was supported by a National Institute for Health Research PhD studentship (NIHR BTRU-2014-10024) during the conduction of this study and reports support from EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart grant n° 116074 outside the submitted work. L. Seekircher reports non-financial support from Sanofi outside the submitted work. H.C. Gerstein reports grants from Sanofi, Eli Lilly, Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Merck, and Abbott, and personal fees from Sanofi, Eli Lilly, Astra Zeneca, Boehringer Ingelheim, Abbott, Novo Nordisk, Merck, Jannsen, Kowa Research Institute, and Cirius outside the submitted work. E. Stroes reports Lecturing/ad-boards fees paid to institution by Amgen, Sanofi-Regeneron, Novartis, Athera, Mylan unrelated to the present work. K. Kapellas reports grants from the National Health and Medical Research Council during the conduct of the study. M. Skilton reports grants from the National Health and Medical Research Council of Australia during the conduct of the study. M.G.A. van Vonderen reports grants from Abbott International and Boehringer Ingelheim during the conduct of the study. S. Kiechl reports grants from the Austrian Promotion Agency FFG outside the submitted work. G. Klingenschmid reports non-financial support from Sanofi and Pfizer outside the submitted work. S.E. Kjeldsen reports personal fees from Bayer, Merck KGaA, MSD, Sanofi, and Takeda outside the submitted work. M.H. Olsen reports grants from the Novo Nordic Foundation outside the submitted work. N. Sattar reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, NAPP Pharmaceuticals, Novo Nordisk, and Sanofi, and grants from Boehringer Ingelheim outside the submitted work. M.P.C. Grooteman reports grants from the Dutch Kidney Foundation, Fresenius Medical Care Netherlands BV, Gambro Sweden, the Twiss Fund, and ZON MW during the conduct of the study. P.J. Blankestijn reports grants from the European Commission and other financial activities from Medtronic, Baxter, and Braun outside the submitted work. M.L. Bots reports grants from AstraZeneca outside the submitted work. M.J. Sweeting reports grants from the German Research Foundation during the conduct of the study. S.G. Thompson reports grants from the UK Medical Research Council, the British Heart Foundation, and the German Research Foundation DFG during the conduct of the study. M.W. Lorenz reports grants from the German Research Foundation DFG during the conduct of the study. Other authors have no conflicts of interests.

Figures

**Figure 1. Intervention effects on cIMT progression plotted against intervention effects on risk for the primary CVD endpoint.**
The intercept of the primary model was 0.92 (95% CI 0.87-0.97). Each bubble represents a trial. Trials with point estimates outside of this area are indicated with the symbol x. The areas of the bubbles are proportional to the inverse variance of the log relative risk for the primary CVD endpoint. The shaded areas around lines-of-fit are 95% prediction intervals. For purpose of presentation, the graph area was limited to -80 to 80 μm/year on the horizontal axis and 0.25 to 4 on the vertical axis. Abbreviations: CI=credible interval. cIMT=carotid intima-media thickness. CVD=cardiovascular disease. RR=relative risk.

**Figure 2. Intervention effects on risk for individual CVD endpoints and all-cause mortality per 10 µm/year slower cIMT progression.**
*The RRs for intercepts are the effects achieved independent of cIMT progression. Abbreviations: CI=credible interval. cIMT=carotid intima-media thickness. CVD=cardiovascular disease. RR=relative risk.

**Figure 3. Intervention effects on cIMT progression plotted against intervention effects on risk for the primary CVD endpoint, according to type of intervention.**
The RRs for intercepts as well as P values for heterogeneity of intercept and slope are provided in Figure 4. The areas of the bubbles are proportional to the inverse variance of the log relative risk for the primary CVD endpoint. For purpose of presentation, the graph area was limited to -80 to 80 μm/year on the horizontal axis and 0.25 to 4 on the vertical axis. Trials with point estimates outside of this area are indicated with the symbol x. Abbreviations: cIMT=carotid intima-media thickness. CVD=cardiovascular disease. RR=relative risk.

**Figure 4. Intervention effects on risk for the primary CVD endpoint per 10 µm/year slower cIMT progression, according to trial characteristics.**
Abbreviations: CCA-IMT=intima-media thickness of the common-carotid-artery. CI=credible interval. cIMT=carotid intima-media thickness. IPD=individual-participant data. RR=relative risk. *P values for heterogeneity. §The RRs for intercepts are the effects achieved independent of cIMT progression.^||Numbers of trials across some subgroups do not sum up to 119 because of missing information or contribution of trials to multiple subgroups.

**Figure 5. Summary of key findings of our study.**
Abbreviations: CI=credible interval. cIMT=carotid intima-media thickness. CVD=cardiovascular disease. RCTs= randomized controlled trials.

See this image and copyright information in PMC

Comment in

Does Reduced Carotid Intima Media Thickness Progression Predict Cardiovascular Risk Reduction?
Shah PK. Shah PK. Circulation. 2020 Aug 18;142(7):643-644. doi: 10.1161/CIRCULATIONAHA.120.048890. Epub 2020 Aug 17. Circulation. 2020. PMID: 32804564 No abstract available.

References

1. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–325. doi: 10.1038/nature10146. - DOI - PubMed
1. Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Völzke H, Tuomainen T-P, Sander D, Plichart M, Catapano AL, Robertson CM, et al. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012;379:2053–2062. doi: 10.1016/S0140-6736(12)60441-3. - DOI - PMC - PubMed
1. Willeit P, Thompson SG, Agewall S, Bergström G, Bickel H, Catapano AL, Chien K-L, de Groot E, Empana J-P, Etgen T, et al. Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Cardiovasc Prev Rehabil. 2016;23:194–205. doi: 10.1177/2047487314560664. - DOI - PMC - PubMed
1. Espeland MA, O'Leary DH, Terry JG, Morgan T, Evans G, Mudra H. Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors. Curr Control Trials Cardiovasc Med. 2005;6:3. doi: 10.1186/1468-6708-6-3. - DOI - PMC - PubMed
1. Peters SAE, den Ruijter HM, Grobbee DE, Bots ML. Results from a carotid intima-media thickness trial as a decision tool for launching a large-scale morbidity and mortality trial. Circ Cardiovasc Imaging. 2013;6:20–25. doi: 10.1161/CIRCIMAGING.112.978114. - DOI - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

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Medical