Bidirectional associations between biological aging, cardiovascular health, and cardiovascular risk: findings from the INSPIRE-T lifespan cohort

Chronological age is a common and non-modifiable factor for chronic disease, but does not fully explain age-related changes. Biological clocks have been developed to explore biological aging mechanisms. They could help identify protective factors against accelerated aging and associated diseases. We aim to assess the association between reduced epigenetic or inflammatory aging and ideal cardiovascular health or cardiovascular risk. We conducted a cross-sectional analysis of participants from the INSPIRE-T cohort. Cardiovascular health (CVH) was assessed using the Life's Essential 8 score. Cardiovascular risk was assessed using the American Framingham risk score (FRS) and the European Systematic Coronary Risk Evaluation (SCORE2) score. Epigenetic and inflammatory aging was calculated from the residuals from linear regression of biological age (based on five epigenetic clocks and one inflammatory clock) and chronological age. Linear and logistic regression models were used. Better CVH has been associated with slower epigenetic aging, particularly in younger subjects and men. Accelerated epigenetic aging measured by GrimAge was associated with an increase cardiovascular risk (for SCORE2: OR = 1.10 95%CI [1.04; 1.16]). No persistent association was found with the inflammatory clock. Our study reported an association between ideal global CVH with reduced epigenetic aging after adjustment for chronological age and gender. This suggests that epigenetic aging may be modifiable through healthy lifestyle and cardiovascular risk management, although a potential underlying causal relationship remains to be established. Moreover, accelerated epigenetic aging is linked to worsening cardiovascular risk, and could be a new risk factor alongside chronological age.

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Journal
GeroScience
Published
2026-04-14
DOI
https://doi.org/10.1007/s11357-026-02251-6
Primary Topic
Cardiovascular Health and Risk Factors
Type
article
Field-Weighted Citation Impact
0.00

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article

Bidirectional associations between biological aging, cardiovascular health, and cardiovascular risk: findings from the INSPIRE-T lifespan cohort

Nicolas Gaudenzio, Bernard Teysseyre, Lauréane Brigitte, Vanina Bongard et al.
GeroScience
Cardiovascular Health and Risk Factors
article

Bidirectional associations between biological aging, cardiovascular health, and cardiovascular risk: findings from the INSPIRE-T lifespan cohort

Nicolas Gaudenzio, Bernard Teysseyre, Lauréane Brigitte, Vanina Bongard, L. Casteilla, Sophie Guyonnet, Néda Tavassoli, Hicham El Costa, Chrystelle Bonnart, Pierre‐Jean Ousset, Philippe Cestac, Brigitte Sallerin, Noélie Davezac, Emeline Müller, Laurent O. Martinez, Nathalie Vergnolle, Fabien Pillard, Jean‐Paul Motta, Isabelle Ader, Laure Rouch, Dominique Langin, Mathilde Strumia, Camille Champigny, Cédric Dray, Céline Deraison, Nicola Coley, Pauline Floch, Pierre Payoux, Pierre Gourdy, Jean-Marc Lemaı̂tre, Claire Rampon, Bruno Guiard, Angelo Parini, Yohan Santin, Mélanie Comté, Patrice Péran, Samuel Thuriot, Tony Macaron, Agathe Milhet, Yves Rolland, Zara Steinmeyer, Antoine Piau, Philippe Valet, Nicolas Fazilleau, Christelle Cantet, Catherine Takeda, Nathalie Daniaud, Fanny Boissou-Parachaud, Marie Dorard, Nabila Jabrane Ferrat, Jean-Philippe Pradere, Marie Faruch, Cyrille Delpierre, Roland Liblau, David Furman, Elodie Paez, Sabine Le Floch, Davide Angioni, Catherine Faisant, Gabor Abellan Van Kan, for the I. H. U. HealthAge INSPIRE/Open Science group, Bénédicte Razat, Luciana Bostan, Sara Djebali, Philipe de Souto Barreto, Anne Bouloumié, Jessica Pontary, Jean-Emmanuel Sarry, Valérie Planat, Jean-Charles Guéry, Françoise Lala, Sandrine Andrieu, Michel Simon, Bruno Vellas
article en

Abstract

Chronological age is a common and non-modifiable factor for chronic disease, but does not fully explain age-related changes. Biological clocks have been developed to explore biological aging mechanisms. They could help identify protective factors against accelerated aging and associated diseases. We aim to assess the association between reduced epigenetic or inflammatory aging and ideal cardiovascular health or cardiovascular risk. We conducted a cross-sectional analysis of participants from the INSPIRE-T cohort. Cardiovascular health (CVH) was assessed using the Life's Essential 8 score. Cardiovascular risk was assessed using the American Framingham risk score (FRS) and the European Systematic Coronary Risk Evaluation (SCORE2) score. Epigenetic and inflammatory aging was calculated from the residuals from linear regression of biological age (based on five epigenetic clocks and one inflammatory clock) and chronological age. Linear and logistic regression models were used. Better CVH has been associated with slower epigenetic aging, particularly in younger subjects and men. Accelerated epigenetic aging measured by GrimAge was associated with an increase cardiovascular risk (for SCORE2: OR = 1.10 95%CI [1.04; 1.16]). No persistent association was found with the inflammatory clock. Our study reported an association between ideal global CVH with reduced epigenetic aging after adjustment for chronological age and gender. This suggests that epigenetic aging may be modifiable through healthy lifestyle and cardiovascular risk management, although a potential underlying causal relationship remains to be established. Moreover, accelerated epigenetic aging is linked to worsening cardiovascular risk, and could be a new risk factor alongside chronological age.

GeroScience
Centre National de la Recherche Scientifique (FR), Buck Institute for Research on Aging (US), Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Centre Hospitalier Universitaire de Toulouse (FR), Hôpital Saint Eloi (FR), Stanford University (US)
Agence Nationale de la Recherche, Université de Toulouse, Région Occitanie Pyrénées-Méditerranée, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 25%
Cardiovascular Health and Risk Factors
DOIOpen Access PDFOpenAlex
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