Citation
Shea, Jonathan W.; Jacobs, David R., Jr.; Howard, Annie Green; Lulla, Anju; Lloyd-Jones, Donald M.; Murthy, Venkatesh L.; Shah, Ravi V.; Trujillo-Gonzalez, Isis; Gordon-Larsen, Penny; & Meyer, Katie A. (2024). Choline Metabolites and Incident Cardiovascular Disease in a Prospective Cohort of Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study. American Journal of Clinical Nutrition, 119(1), 29-38. PMCID: PMC10808833Abstract
BACKGROUND: The potential role for choline metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD) has garnered much attention, but there have been limited data from diverse population-based cohorts. Furthermore, few studies have included circulating choline and betaine, which can serve as precursors to TMAO, and may independently influence CVD.OBJECTIVE: We quantified prospective associations between three choline metabolites and 19-year incident CVD in a population-based cohort, and tested effect modification of metabolite-CVD associations by kidney function.
METHODS: Data were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort with recruitment from 4 U.S. urban centers (year 0: 1985-86; n=5,115; ages 18-30). The analytic sample included 3,444 White and Black males and females, aged 33-45, who attended the Year 15 follow-up exam and did not have prevalent CVD. TMAO, choline, and betaine were quantitated from stored plasma (-70° C) using liquid-chromatography mass-spectrometry. 19-year incident CVD events (n=221), including coronary heart disease and stroke, were identified through adjudicated hospitalization records and linkage with the National Death Register.
RESULTS: Plasma choline was positively associated with CVD in Cox proportional hazards regression analysis adjusted for demographics, health behaviors, CVD risk factors, and metabolites [hazard ratio (95% CI): 1.24 (1.09, 1.40) per SD-unit choline]. TMAO and betaine were not associated with CVD in identically adjusted analysis. There was statistical evidence for effect modification by kidney function with CVD positively associated with TMAO, and negatively associated with betaine at lower values of estimated glomerular filtration rate (interaction p-values: 0.0046 and 0.020, respectively).
CONCLUSIONS: Our findings are consistent with a positive association between plasma choline and incident CVD. Among participants with lower kidney function, TMAO was positively, and betaine negatively, associated with CVD. These results further our understanding of the potential role for choline metabolism on CVD risk.
URL
http://dx.doi.org/10.1016/j.ajcnut.2023.10.012Reference Type
Journal ArticleYear Published
2024Journal Title
American Journal of Clinical NutritionAuthor(s)
Shea, Jonathan W.Jacobs, David R., Jr.
Howard, Annie Green
Lulla, Anju
Lloyd-Jones, Donald M.
Murthy, Venkatesh L.
Shah, Ravi V.
Trujillo-Gonzalez, Isis
Gordon-Larsen, Penny
Meyer, Katie A.
Article Type
RegularPMCID
PMC10808833Data Set/Study
Coronary Artery Risk Development in Young Adults (CARDIA) StudyContinent/Country
United StatesState
NonspecificRace/Ethnicity
BlackWhite