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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e006524 |
| Tidsskrift | Journal of the American Heart Association |
| Vol/bind | 6 |
| Udgave nummer | 11 |
| ISSN | 2047-9980 |
| DOI | |
| Status | Udgivet - 2017 |
| Udgivet eksternt | Ja |
Bibliografisk note
Funding Information:2009–13906-C02 and AGL2010–22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalućıa (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Gener-alitat Valenciana (ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and Regional Government of Navarra (P27/2011). Guasch-Ferréwas 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). None of the funding sources played a role in the design, collection, analysis, or interpretation of the data or in the decision to submit the article for publication.
Funding Information:
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 Cardiovas-culares (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-
Funding Information:
Hu and Ros received grants from the California Walnut Commission. Martínez-González and Salas-Salvadó received grants from the International Nut Council. None of the other authors has a relevant conflict of interest to report related to this research.
Publisher Copyright:
© 2017 The Authors.