Carotid Stiffness Is Associated with Incident Stroke A Systematic Review and Individual Participant Data Meta-Analysis

Thomas T. Van Sloten, Sanaz Sedaghat, Stéphane Laurent, Gérard M. London, Bruno Pannier, M. Arfan Ikram, Maryam Kavousi, Francesco Mattace-Raso, Oscar H. Franco, Pierre Boutouyrie, Coen D.A. Stehouwer

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Background Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent. Objectives This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV. Methods This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual-level data of all cohort studies with available data on carotid stiffness and cfPWV. Results Ten studies (n = 22,472) were included in the aggregate data meta-analysis and 4 (n = 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]). Conclusions Carotid stiffness is associated with incident stroke independently of CV factors and aortic stiffness. In addition, carotid stiffness improves stroke risk prediction beyond Framingham and aortic stiffness.

Original languageEnglish (US)
Pages (from-to)2116-2125
Number of pages10
JournalJournal of the American College of Cardiology
Issue number19
StatePublished - 2015
Externally publishedYes

Bibliographical note

Funding Information:
The Hoorn Study was supported by grants from the Netherlands Organization for Health Research and Development; the Netherlands Heart Foundation; and the Dutch Diabetes Foundation. The Nephrotest Study was supported by grants from Programme Hospitalier de Recherche Clinique; French Ministry of Health; and National Institute for Health and Medical Research (INSERM). The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organisation for Scientific Research; the Netherlands Organisation for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Drs. van Sloten and Stehouwer are supported by the European Regional Development Fund as part of OP-ZUID, the province of Limburg, the Department of Economic Affairs of the Netherlands (grant 31O.041), Stichting the Weijerhorst, the Pearl String Initiative Diabetes, the Cardiovascular Centre Maastricht, Cardiovascular Research Institute Maastricht, School for Nutrition, Toxicology and Metabolism, Stichting Annadal, and Health Foundation Limburg. Drs. Laurent, London, Pannier, and Boutouyrie are supported by Assistance Piblique Hopitaux de Paris, Paris Descartes University, and INSERM. Dr. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. The funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. van Sloten and Sedaghat contributed equally to this work.

Publisher Copyright:
© 2015 American College of Cardiology Foundation.


  • arterial stiffness
  • cardiovascular disease
  • risk classification


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