Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial

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  • Cristina Razquin
  • Miguel Ruiz-Canela
  • Estefania Toledo
  • Clary B. Clish
  • Jesús F. García-Gavilán
  • Clemens Wittenbecher
  • Angel Alonso-Gómez
  • Montse Fitó
  • Liming Liang
  • Dolores Corella
  • Enrique Gómez-Gracia
  • Ramon Estruch
  • Miquel Fiol
  • Jose M. Santos-Lozano
  • Luis Serra-Majem
  • Emilio Ros
  • Fernando Aros
  • Jordi Salas-Salvadó
  • Frank B. Hu
  • Miguel A. Martínez-González

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.

OriginalsprogEngelsk
Artikelnummer270
TidsskriftInternational Journal of Molecular Sciences
Vol/bind24
Antal sider12
ISSN1661-6596
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the National Institutes of Health research grant R01HL118264 (1R01HL118264-01/2R01HL118264-05/2R01HL118264-09). The PREDIMED trial was supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140 to Ramón Estruch during 2003–2005; RTIC RD 06/0045 to Miguel A. Martínez-González during 2006–2013 and through the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición [CIBEROBN]), and by grants from the Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), the Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, PI13/00462 and JR17/00022), the Ministerio de Ciencia e Innovación (AGL-2009–13906-C02, AGL2010–22319-C03 and SAF2016–80532-R), the Fundación Mapfre 2010 (no role in the design, implementation, analysis or interpretation of the data), the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, PROMETEO 17/2017 and CS2011-AP-042), the Fundació La Marató-TV3 (grants 294/C/2015 and 538/U/2016 (no role in the design, implementation, analysis or interpretation of the data)) and the Regional Government of Navarra (P27/2011). Marta Guasch-Ferré was supported by the American Diabetes Association, grant #1-18-PMF-029. Jordi Salas-Salvadó was partially supported by ICREA under the ICREA Academia programme. Wittenbecher was supported by the SciLifeLab & Wallenberg Data Driven Life Science Program (grant: KAW 2020.0239). Marta Guasch-Ferré was supported by NNF18CC0034900.

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