Association of Intima‐Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta‐Analysis of 20 Prospective Studies Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Abstract Background The association between common carotid artery intima‐media thickness (CCA‐IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA‐IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta‐analysis of 20 prospective studies from the Proof‐ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA‐IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA‐IMT was 0.71 mm (SD, 0.17 mm). Over a median follow‐up of 5.9 years (5th–95th percentile, 1.9–19.0 years), 8278 individuals developed first‐ever carotid plaque. We combined study‐specific odds ratios (ORs) for incident carotid plaque using random‐effects meta‐analysis. Baseline CCA‐IMT was approximately log‐linearly associated with the odds of developing carotid plaque. The age‐, sex‐, and trial arm–adjusted OR for carotid plaque per SD higher baseline CCA‐IMT was 1.40 (95% CI, 1.31–1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low‐ and high‐density lipoprotein cholesterol, and lipid‐lowering and antihypertensive medication was 1.34 (95% CI, 1.24–1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29–1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large‐scale individual participant data meta‐analysis demonstrated that CCA‐IMT is associated with the long‐term risk of developing first‐ever carotid plaque, independent of traditional cardiovascular risk factors. Keywords: carotid intima‐media thickness, carotid plaque, individual participant data meta‐analysis, prospective studies Subject Categories: Epidemiology, Cardiovascular Disease, Ultrasound
SHOW FULL ABSTRACT Lena Tschiderer, Lisa Seekircher, Raffaele Izzo, Costantino Mancusi, Maria V Manzi, Damiano Baldassarre, Mauro Amato, Elena Tremoli, Fabrizio Veglia, Tomi‐Pekka Tuomainen, Jussi Kauhanen, Ari Voutilainen, Bernhard Iglseder, Lars Lind, Tatjana Rundek, Moise Desvarieux, Akihiko Kato, Eric de Groot, Gülay Aşçi, Ercan Ok, Stefan Agewall, Joline W J Beulens, Christopher D Byrne, Philip C Calder, Hertzel C Gerstein, Paolo Gresele, Gerhard Klingenschmid, Michiaki Nagai, Michael H Olsen, Grace Parraga, Maya S Safarova, Naveed Sattar, Michael Skilton, Coen D A Stehouwer, Heiko Uthoff, Michiel A van Agtmael, Amber A van der Heijden, Dorota A Zozulińska‐Ziółkiewicz, Hyun‐Woong Park, Moo‐Sik Lee, Jang‐Ho Bae, Oscar Beloqui, Manuel F Landecho, Matthieu Plichart, Pierre Ducimetiere, Jean Philippe Empana, Lena Bokemark, Göran Bergström, Caroline Schmidt, Samuela Castelnuovo, Laura Calabresi, Giuseppe D Norata, Liliana Grigore, Alberico Catapano, Dong Zhao, Miao Wang, Jing Liu, M Arfan Ikram, Maryam Kavousi, Michiel L Bots, Michael J Sweeting, Matthias W Lorenz, Peter Willeit
1
Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria 2
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy 3
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy 4
Centro Cardiologico Monzino Stituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy 5
Maria Cecilia Hospital, Cotignola (Ravenna), Italy 6
Klinik für Neurologie, Krankenhaus Nordwest, Frankfurt am Main, Germany 7
Department of Clinical Sciences, Danderyd Hospital Division of Cardiology, Karolinska Institutet, Stockholm, Sweden 8
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland 9
Department of Geriatric Medicine, Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft GmbH Christian‐Doppler‐Klinik, Salzburg, Austria 10
Department of Geriatric Medicine, Paracelsus Medical University, Salzburg, Austria 11
Department of Medicine, Uppsala University, Uppsala, Sweden 12
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 13
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 14
METHODS Core, Centre de Recherche Epidémiologie et Statistique Paris Sorbonne Cité, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1153, Paris, France 15
Blood Purification Unit, Hamamatsu University Hospital, Hamamatsu, Japan 16
Imagelabonline and Cardiovascular, Erichem, the Netherlands 17
Department of Gastroenterology and Hepatology, Amsterdam University Medical Center–Academic Medical Centre, Amsterdam, the Netherlands 18
Nephrology Department, Ege University School of Medicine, Bornova‐Izmir, Turkey 19
Institute of Clinical Sciences, University of Oslo, Oslo, Norway 20
Department of Epidemiology and Data Science, Amsterdam University Medical Center–Location Vrije Universiteit Medical Center, Amsterdam, the Netherlands 21
School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK 22
Southampton National Institute for Health and Care Research, Biomedical Research Centre, University Hospital Southampton, Southampton, UK 23
Department of Medicine and Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada 24
Hamilton General Hospital, Hamilton, Ontario, Canada 25
Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy 26
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria 27
Department of Internal Medicine, General Medicine and Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan 28
Department of Internal Medicine, Holbaek Hospital, University of Southern Denmark, Odense, Denmark 29
Department of Medical Biophysics, Robarts Research Institute, Western University, London, ON, Canada 30
Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, KS 31
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK 32
Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia 33
Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands 34
Department of Angiology, University Hospital Basel, Basel, Switzerland 35
Department of Internal Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands 36
Department of General Practice, Amsterdam University Medical Center–Location Vrije Universiteit Medical Center, Amsterdam, the Netherlands 37
Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland 38
Division of Cardiology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong‐si, South Korea 39
Department of Preventive Medicine, College of Medicine, Konyang University, Daejeon, South Korea 40
Department of Occupational and Environmental Medicine, Konyang University Hospital, Daejeon, South Korea 41
Heart Center, Konyang University Hospital, Daejeon, South Korea 42
Department of Cardiology, Konyang University College of Medicine, Daejeon, South Korea 43
Department of Internal Medicine, University Clinic of Navarra, Navarra, Spain 44
Paris Cardiovascular Research Centre, University Paris Descartes, Paris, France 45
Fondation Santé Service, Hospital at Home, Levallois‐Perret, France 46
Faculty of Medicine, University Paris Descartes, Paris, France 47
Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden 48
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 49
Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västragötaland, Gothenburg, Sweden 50
Centro Dislipidemie, Aziende Socio Sanitarie Territoriali Grande Ospedale Metropolitano Niguarda, Milan, Italy 51
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy 52
Società Italiana per lo Studio dell'Aterosclerosi Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy 53
Stituto di Ricovero e Cura a Carattere Scientifico Multimedica, Milan, Italy 54
Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 55
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands 56
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands 57
Department of Health Sciences, University of Leicester, Leicester, UK 58
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 59
Department of Neurology, Goethe University, Frankfurt am Main, Germany 