|Roe, Annie - UNIVERSITY OF IDAHO|
|Zhang, Shucha - UNIVERSITY OF NORTH CAROLINA|
|Bhadelia, Rafeeque - BETH ISRAEL DEACONESS MEDICAL CENTER|
|Johnson, Elizabeth - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
|Lichtenstein, Alice - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
|Rogers, Gail - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
|Rosenberg, Irwin - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
|Smith, Caren - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
|Zeisel, Steven - UNIVERSITY OF NORTH CAROLINA|
|Scott, Tammy - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY|
Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2017
Publication Date: 3/29/2017
Citation: Roe, A.J., Zhang, S., Bhadelia, R.A., Johnson, E.J., Lichtenstein, A.H., Rogers, G.T., Rosenberg, I.H., Smith, C.E., Zeisel, S.E., Scott, T. 2017. Choline and its metabolites are differently associated with cardiometabolic risk factors, cardiovascular history and MRI documented cerebrovascular disease in older adults. American Journal of Clinical Nutrition. 105:1283-1290. https://doi.org/10.3945/ajcn.116.137158.
Interpretive Summary: Choline is an essential nutrient necessary for neurodevelopment and the health and integrity of cells. It is also necessary as a precursor to acetylcholine, a neurotransmitter important for memory. There is a potential role of choline in cardiovascular and cerebrovascular disease, however, because of choline's possible link to plaque buildup in arteries and the role of some choline-related compounds in the production of cholesterol, including the "bad" cholesterol LDL. In this study, we evaluated the associations of choline and choline-related compounds in the blood with cardiovascular risk factors, history of cardiovascular disease, and cerebrovascular pathology in approximately 300 people over 60 years old who had undergone magnetic resonance imaging (MRI) of the brain. We found that choline and its metabolites (the compounds into which it is broken down) had different associations with cardio and cerebrovascular risk factors (such as LDL and HDL cholesterol and triglycerides) and with subtypes of vascular disease. People with higher concentrations of choline were more likely to have a history of cardiovascular disease and stroke but were less likely to have small blood-vessel disease in the brain. Future research will need to evaluate these relationships over time and to examine potential interactions between an individual's diet and genetic makeup in order to better understand these associations.
Technical Abstract: Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology. Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n=296; mean +/- SD age: 73 +/- 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilution-multiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small- and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology. Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower highdensity lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile (higher LDL cholesterol and triglycerides). Conclusion: Choline and its metabolites have differential associations with cardiometabolic risk factors and subtypes of vascular disease, thereby suggesting differing roles in the pathogenesis of cardiovascular and cerebral large-vessel disease compared with that of small-vessel disease.