Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

Guasch Ferré, Marta; Hu, Frank B.; Ruiz-Canela, Miguel; Bulló, Mònica; Toledo, Estefania; Wang, Dong D.; Corella, Dolores; Gómez Gracia, Enrique; Fiol, Miquel; Estruch, Ramón; Lapetra, José; Fitó Colomer, Montserrat; Arós, Fernando; Serra-Majem, Luis; Ros, Emilio; Dennis, Courtney; Liang, Liming; Clish, Clary B.; Martínez-González, Miguel Ángel, 1957-; Salas-Salvadó, Jordi

Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study

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dc.contributor.author Guasch Ferré, Martaca
dc.contributor.author Hu, Frank B.ca
dc.contributor.author Ruiz-Canela, Miguelca
dc.contributor.author Bulló, Mònicaca
dc.contributor.author Toledo, Estefaniaca
dc.contributor.author Wang, Dong D.ca
dc.contributor.author Corella, Doloresca
dc.contributor.author Gómez Gracia, Enriqueca
dc.contributor.author Fiol, Miquelca
dc.contributor.author Estruch, Ramónca
dc.contributor.author Lapetra, Joséca
dc.contributor.author Fitó Colomer, Montserratca
dc.contributor.author Arós, Fernandoca
dc.contributor.author Serra-Majem, Luisca
dc.contributor.author Ros, Emilioca
dc.contributor.author Dennis, Courtneyca
dc.contributor.author Liang, Limingca
dc.contributor.author Clish, Clary B.ca
dc.contributor.author Martínez-González, Miguel Ángel, 1957-ca
dc.contributor.author Salas-Salvadó, Jordica
dc.date.accessioned 2018-06-20T07:13:30Z
dc.date.available 2018-06-20T07:13:30Z
dc.date.issued 2017
dc.description.abstract BACKGROUND: The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. METHODS AND RESULTS: We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P<0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD. CONCLUSIONS: A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk.
dc.description.sponsorship This work was supported by NIH research grant HL118264. The PREDIMED trial was supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial (RTIC G03/140 to Estruch; RTIC RD 06/0045 to Martínez‐González) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición; and by grants from Centro Nacional de Investigaciones Cardiovasculares (06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, and PI13/00462), Ministerio de Ciencia e Innovación (AGL‐2009–13906‐C02 and AGL2010–22319‐C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), 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, and CS2011‐AP‐042), and Regional Government of Navarra (P27/2011). Guasch‐Ferré was supported by a postdoctoral fellowship granted by the Agency for Administration of University and Research Grants of the Autonomous Government of Catalonia (2014‐BP‐A 00017).
dc.format.mimetype application/pdf
dc.identifier.citation Guasch-Ferré M3, Hu FB, Ruiz-Canela M7, Bulló M, Toledo E7, Wang DD et al. Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study. J Am Heart Assoc. 2017 Oct 28;6(11). pii: e006524. DOI: 10.1161/JAHA.117.006524
dc.identifier.doi http://dx.doi.org/10.1161/JAHA.117.006524
dc.identifier.issn 2047-9980
dc.identifier.uri http://hdl.handle.net/10230/34934
dc.language.iso eng
dc.publisher Wileyca
dc.relation.ispartof Journal of the American Heart Association. 2017 Oct 28;6(11):e006524
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL‐2009–13906‐C02
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL-2010–22319‐C03
dc.rights Copyright © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.subject.keyword Mediterranean diet
dc.subject.keyword Cardiovascular disease
dc.subject.keyword Choline
dc.subject.keyword Gut microbiota
dc.subject.keyword Metabolomics
dc.subject.other Dieta -- Mediterrània, Regió de la
dc.subject.other Plasma sanguini
dc.subject.other Sistema cardiovascular -- Malalties
dc.title Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Studyca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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