Abstract
Vascular aging is the accumulation of functional and structural changes of vessels throughout life. While earlier studies have shown that single manifestation of vascular aging is associated with an increased risk of cardiovascular disease (CVD), it is unknown how the different manifestations of vascular aging cluster at the individual level, and whether individuals with different vascular aging patterns have different risk of progression to overt CVD. Here, we identify three patterns of vascular aging including healthy vascular aging (HVA), arteriosclerosis and atherosclerosis. Vascular aging manifestations were evaluated non-invasively by carotid ultrasound methods. The main and the validation analysis were conducted on 8360 and 2086 participants in two separate prospective cohorts. We find that arteriosclerosis and atherosclerosis compared to HVA clusters are independent predictors of CVD, and improve risk stratification for stroke among those at intermediate risk. Vascular aging evaluation may help identify those at increased risk of CVD.
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Data availability
The data from the Paris Prospective Study III study, including the raw data supporting the present findings, cannot be shared publicly due to the privacy of individuals who participated in the study. However, pseudo-anonymized data can be made available from the corresponding author (*jean-philippe.empana@inserm.fr) upon reasonable request, pending evaluation by the Paris Prospective Study III scientific committee of the research application. The expected timeframe for response to access requests is generally three months. Source data supporting the figures and main analyses and code to reproduce them are provided within this manuscript. Data from the Rotterdam study cannot be made freely available in a public repository because of restrictions based on privacy regulations and informed consent of the participants. The data can be obtained upon request. Requests should be directed towards the management team of the Rotterdam Study (secretariat.epi@erasmusmc.nl), which has a protocol for approving data requests. The expected timeframe for response to access requests is generally three months. Source data are provided with this paper.
Code availability
The statistical code that supports the study findings are provided in the data source file.
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Acknowledgements
We thank the assistant research team who has performed the study recruitment of PPS3 study participants, the medical and technical staff of the IPC Center, and the Platform for Biological Resources (PRB) of the Hôpital Européen Georges Pompidou for the management of the biobank. We thank the assistant research team of PPS3, who performed the follow-up of the participants. PPS3 is organized under an agreement between INSERM and the IPC Center and between INSERM and the Resources Biologiques de l’Hôpital European Georges Pompidou, Paris, France. We also thank the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés (CNAM-TS, France) and the Caisse Primaire d’Assurance Maladie de Paris (CPAM-P, France) for helping make this study possible. The PPS3 Study was supported by grants from the National Research Agency (ANR, JPE), the Research Foundation for Hypertension (FR-HTA, PB), the Research Institute in Public Health (IRESP, JPE), the Region Ile de France (Domaine d’Intérêt Majeur, xj), the INSERM International Research Project grant (JPE), and a European Horizon H2020 grant (XJ). The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; The Netherlands Organisation for Scientific Research (NWO); The Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); The Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The contribution of inhabitants, general practitioners, and pharmacists of the Ommoord district to the Rotterdam Study is gratefully acknowledged. R.E.C. is supported by the National Health and Medical Research Council of Australia (reference: 2009005) and by a National Heart Foundation Future Leader Fellowship (reference: 105636).
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X.J., P.B., and J.P.E. conceived and/or designed the project. X.J., P.B., J.P.E., F.M.R., and M.K. contributed to the acquisition of data. M.A. and J.P.E. contributed to data analysis. T.V.S., M.A., P.B., R.M.B., and J.P.E. contributed to interpretation of data. T.V.S. and J.P.E. drafted the initial manuscript. All authors provided substantive contributions to the revisions and approve the final version of the submitted manuscript.
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van Sloten, T., Boutouyrie, P., Abouqateb, M. et al. Clusters of vascular aging manifestations predict incident cardiovascular events in the community. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70137-4
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DOI: https://doi.org/10.1038/s41467-026-70137-4


