Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort
Background Growth differentiation factor 15 (GDF‐15) levels are emerging as a candidate biomarker of aging. The present study aimed to: (1) characterize the association of GDF‐15 with the continuum of arterial stiffening, assessed as carotid‐femoral pulse wave velocity, as age increases; (2) determi...
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Wiley
2025-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036253 |
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| author | Richard Oppong Valeria Orru Michele Marongiu Yong Qian Carlo Sidore Alessandro Delitala Marco Orru Antonella Mulas Maria Grazia Piras Christopher H. Morrell Sandra Lai David Schlessinger Myriam Gorospe Francesco Cucca Edoardo Fiorillo Jun Ding Edward G. Lakatta Angelo Scuteri |
| author_facet | Richard Oppong Valeria Orru Michele Marongiu Yong Qian Carlo Sidore Alessandro Delitala Marco Orru Antonella Mulas Maria Grazia Piras Christopher H. Morrell Sandra Lai David Schlessinger Myriam Gorospe Francesco Cucca Edoardo Fiorillo Jun Ding Edward G. Lakatta Angelo Scuteri |
| author_sort | Richard Oppong |
| collection | DOAJ |
| description | Background Growth differentiation factor 15 (GDF‐15) levels are emerging as a candidate biomarker of aging. The present study aimed to: (1) characterize the association of GDF‐15 with the continuum of arterial stiffening, assessed as carotid‐femoral pulse wave velocity, as age increases; (2) determine the predictive role of serum GDF‐15 levels on mortality; and (3) identify genetic determinants of serum GDF‐15 levels. Methods and Results Serum levels of GDF‐15 and established cardiovascular risk factors, including pulse wave velocity, were assessed in a large (4736 individual) Sardinian population. Serum levels of GDF‐15, which can be reliably measured repeatedly over time, increase with age; are associated with a stiffer aorta; “mediate” a large proportion of the age‐associated increase in arterial stiffness; pose risks because of their association with greater mortality; and are significantly associated with the variant rs11549407, which causes thalassemia major in homozygosity. Conclusions Because of its consistent ability to predict functional and clinical outcomes, including all‐cause mortality, we conclude that GDF‐15 serum levels serve as a robust biomarker for the continuum from health to the emergence of clinical disease during aging and, subsequently, to the likelihood of mortality. |
| format | Article |
| id | doaj-art-e59076103cac4b59a2ecf8b2d37e3129 |
| institution | DOAJ |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-e59076103cac4b59a2ecf8b2d37e31292025-08-20T03:07:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-05-01141010.1161/JAHA.124.036253Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population CohortRichard Oppong0Valeria Orru1Michele Marongiu2Yong Qian3Carlo Sidore4Alessandro Delitala5Marco Orru6Antonella Mulas7Maria Grazia Piras8Christopher H. Morrell9Sandra Lai10David Schlessinger11Myriam Gorospe12Francesco Cucca13Edoardo Fiorillo14Jun Ding15Edward G. Lakatta16Angelo Scuteri17National Institute on Aging – Intramural Research Program NIH Baltimore MDIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyNational Institute on Aging – Intramural Research Program NIH Baltimore MDIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyDepartment Surgical, and Experimental Sciences University of Sassari Sassari ItalyIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyNational Institute on Aging – Intramural Research Program NIH Baltimore MDIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyNational Institute on Aging – Intramural Research Program NIH Baltimore MDNational Institute on Aging – Intramural Research Program NIH Baltimore MDIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyIstituto di Ricerca Genetica e Biomedica (IRGB) Consiglio Nazionale delle Ricerche (CNR) Lanusei (NU) ItalyNational Institute on Aging – Intramural Research Program NIH Baltimore MDNational Institute on Aging – Intramural Research Program NIH Baltimore MDInternal Medicine Unit Policlinico Universitario Monserrato – Azienda Ospedaliera Universitaria (AOU) Cagliari Cagliari ItalyBackground Growth differentiation factor 15 (GDF‐15) levels are emerging as a candidate biomarker of aging. The present study aimed to: (1) characterize the association of GDF‐15 with the continuum of arterial stiffening, assessed as carotid‐femoral pulse wave velocity, as age increases; (2) determine the predictive role of serum GDF‐15 levels on mortality; and (3) identify genetic determinants of serum GDF‐15 levels. Methods and Results Serum levels of GDF‐15 and established cardiovascular risk factors, including pulse wave velocity, were assessed in a large (4736 individual) Sardinian population. Serum levels of GDF‐15, which can be reliably measured repeatedly over time, increase with age; are associated with a stiffer aorta; “mediate” a large proportion of the age‐associated increase in arterial stiffness; pose risks because of their association with greater mortality; and are significantly associated with the variant rs11549407, which causes thalassemia major in homozygosity. Conclusions Because of its consistent ability to predict functional and clinical outcomes, including all‐cause mortality, we conclude that GDF‐15 serum levels serve as a robust biomarker for the continuum from health to the emergence of clinical disease during aging and, subsequently, to the likelihood of mortality.https://www.ahajournals.org/doi/10.1161/JAHA.124.036253agingcentral arterial stiffnessGDF‐15genetic markerspulse wave velocity |
| spellingShingle | Richard Oppong Valeria Orru Michele Marongiu Yong Qian Carlo Sidore Alessandro Delitala Marco Orru Antonella Mulas Maria Grazia Piras Christopher H. Morrell Sandra Lai David Schlessinger Myriam Gorospe Francesco Cucca Edoardo Fiorillo Jun Ding Edward G. Lakatta Angelo Scuteri Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aging central arterial stiffness GDF‐15 genetic markers pulse wave velocity |
| title | Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort |
| title_full | Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort |
| title_fullStr | Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort |
| title_full_unstemmed | Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort |
| title_short | Age‐Associated Increase in Growth Differentiation Factor 15 Levels Correlates With Central Arterial Stiffness and Predicts All‐Cause Mortality in a Sardinian Population Cohort |
| title_sort | age associated increase in growth differentiation factor 15 levels correlates with central arterial stiffness and predicts all cause mortality in a sardinian population cohort |
| topic | aging central arterial stiffness GDF‐15 genetic markers pulse wave velocity |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036253 |
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