Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial
Journal article, 2023
Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61–0.99); 0.67 (0.51–0.86) and 0.75 (0.59–0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14–1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine.
case-cohort
metabolomics
amino acids
peripheral artery disease
PREDIMED
Author
Cristina Razquin
University of Navarra
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Miguel Ruiz-Canela
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
University of Navarra
Estefania Toledo
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
University of Navarra
Clary B. Clish
Broad Institute
Marta Guasch-Ferré
University of Copenhagen
Harvard School of Public Health
Jesús F. García-Gavilán
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Institut d'Investigació Sanitària Pere Virgili
Clemens Wittenbecher
Harvard School of Public Health
Chalmers, Life Sciences, Food and Nutrition Science
Angel Alonso-Gómez
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Hospital Universitario Araba
Montse Fitó
Hospital del Mar Medical Research Institute
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Liming Liang
Harvard School of Public Health
Dolores Corella
Universitat de Valencia
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Enrique Gómez-Gracia
University of Malaga
Ramon Estruch
University of Barcelona
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Miquel Fiol
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Hospital Universitario Son Espases
Jose M. Santos-Lozano
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Research Unit
Luis Serra-Majem
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Universidad de Las Palmas de Gran Canaria
Emilio Ros
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
University of Barcelona
Fernando Aros
Hospital Universitario Araba
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Jordi Salas-Salvadó
Institut d'Investigació Sanitària Pere Virgili
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Frank B. Hu
Channing Division of Network Medicine
Harvard School of Public Health
Miguel A. Martínez-González
Harvard School of Public Health
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
University of Navarra
International Journal of Molecular Sciences
16616596 (ISSN) 14220067 (eISSN)
Vol. 24 1 270Subject Categories (SSIF 2011)
Endocrinology and Diabetes
Cardiac and Cardiovascular Systems
Nutrition and Dietetics
DOI
10.3390/ijms24010270
PubMed
36613713