Association of Intima‐Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta‐Analysis of 20 Prospective Studies
Authors: Tschiderer Lena , Seekircher Lisa , Izzo Raffaele , Mancusi Costantino , Manzi Maria V. , Baldassarre Damiano , Amato Mauro , Tremoli Elena , Veglia Fabrizio , Tuomainen Tomi‐Pekka , Kauhanen Jussi , Voutilainen Ari , Iglseder Bernhard , Lind Lars , Rundek Tatjana , Desvarieux Moise , Kato Akihiko , de Groot Eric , Aşçi Gülay , Ok Ercan , Agewall Stefan , Beulens Joline W. J. , Byrne Christopher D. , Calder Philip C. , Gerstein Hertzel C. , Gresele Paolo , Klingenschmid Gerhard , Nagai Michiaki , Olsen Michael H. , Parraga Grace , Safarova Maya S. , Sattar Naveed , Skilton Michael , Stehouwer Coen D. A. , Uthoff Heiko , van Agtmael Michiel A. , van der Heijden Amber A. , Zozulińska‐Ziółkiewicz Dorota A. , Park Hyun‐Woong , Lee Moo‐Sik , Bae Jang‐Ho , Beloqui Oscar , Landecho Manuel F. , Plichart Matthieu , Ducimetiere Pierre , Empana Jean Philippe , Bokemark Lena , Bergström Göran , Schmidt Caroline , Castelnuovo Samuela , Calabresi Laura , Norata Giuseppe D. , Grigore Liliana , Catapano Alberico , Zhao Dong , Wang Miao , Liu Jing , Ikram M. Arfan , Kavousi Maryam , Bots Michiel L. , Sweeting Michael J. , Lorenz Matthias W. , Willeit Peter ,   Proof‐ATHERO Study Group
Published: June 2023

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;
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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];
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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.