Among the 14,430 participants in this study, the median intake of choline was 302 mg/day in men, 271 mg/day in women, 286 mg/day in whites and 274 mg/day in blacks. For betaine the median intakes were 101 mg/day in men, 89 mg/day in women, 95 mg/day in whites and 91 mg/day in blacks. The distribution of the main baseline characteristics of the study population according to gender is presented in Table . The correlations between the interrelated nutrients choline, folate and methionine were as follows: 0.35 for choline-folate, 0.45 for choline-methionine and 0.55 for folate-methionine. In our population, the top five contributors of choline intake were red meat – side dish (11.4%), eggs (11.1%), red meat – main dish (10.4%), low fat milk (8.3%) and chicken without skin (8.3%). The top five contributors of betaine were dark bread (24.9%), white bread (18.1%), spinach (10.4%), cold breakfast cereals (8.2%) and pasta (4.7%). The top ten food items (and the quantity per serving) on the FFQ that contribute to the intake of these two micronutrients in the ARIC population are presented in Table .
Distribution of baseline characteristics of the ARIC Study population (N = 14,430) according to gender.
Top ten food items on the FFQ that contribute to the intake of choline and betaine among 14,430 participants in the ARIC Study.
Over an average of 14 years of follow-up (1987–2002), 1072 validated incident CHD events occurred. Neither higher intakes of dietary choline nor betaine were significantly associated with incident CHD. Compared with the lowest quartile of intake, incident CHD risk was 22% higher [HR = 1.22 (0.91, 1.64)] and 14% higher [HR = 1.14 (0.85, 1.53)] in the highest quartile of choline and choline plus betaine respectively, controlling for age, sex, education, total energy intake, and dietary intakes of folate, methionine and vitamin B6 (Table ). Further adjustment for race, diabetes status, ARIC field center and dietary cholesterol, vitamins B12 and B2, as well as for other CHD risk factors, such as obesity (defined as a body mass index, BMI, higher than 30), hypertension, smoking status and estimated family history of CHD, produced similar risk estimates.
Hazard rate ratios (and 95% CI) for CHD across quartiles of dietary intakes among 14,430 participants in the ARIC Study.
Because eggs, milk and green vegetables are important contributors to choline and betaine intake, we performed sensitivity-type analyses to further adjust for intake of saturated fatty acids, animal fat, dietary fiber and animal protein. The hazard ratios across the quartiles of choline and total choline intakes (considering the same lowest quartile as referent, and adjusting for all confounders considered in models #2, Table , namely age, sex, education, total energy intake, dietary intakes of folate, methionine, vitamin B6, race, diabetes status, ARIC field center, menopausal status and dietary cholesterol) remained practically unchanged, suggesting that the higher risk associated with the highest intake is not due to confounding from uncontrolled dietary factors (Table ).
No effect measure modification was detected by sex, menopausal status, race, ARIC center, education or folate intake analyzed as a continuous variable. Correction for measurement error in the dietary intake of choline and related nutrients, using models containing continuous nutrient variables, provided similar results. For choline, the hazard ratio for those in the highest quartile, compared with those in the lowest, was 1.34 (0.98, 1.85). When using the bootstrapping procedure and obtained the 95% confidence interval for the corrected choline regression coefficient, the risk estimate remained non-significant.
To examine the effect of folate fortification that was mandated after January 1998 we conducted a supplemental analysis with exclusion of events that occurred prior to that date. For choline and for choline plus betaine the risk estimates were weakened and still not significant. Specifically, compared with the lowest quartile, the hazard ratios for choline were 0.80 (0.62, 1.04), 1.01 (0.76, 1.36) and 0.97 (0.64, 1.47) for the second, the third and the fourth quartile of the dietary intake, respectively. For choline plus betaine, the risks of incident CHD by quartiles were 0.86 (0.67, 1.11), 0.98 (0.73, 1.30) and 0.90 (0.61, 1.35), respectively.
In order to use the repeated measurement of dietary intake completed during visit 3 (1993–1995) in all ARIC participants, we did an additional analysis in which we investigated the risk of incident CHD among participants which did not develop this outcome before this visit. For both choline and for choline plus betaine the risk estimates remained similar. Specifically, compared with the lowest quartile, the hazard ratios for choline were 1.05 (0.81, 1.37), 0.94 (0.70, 1.30) and 1.09 (0.74, 1.59) for the second, the third and the fourth quartile of the dietary intake, respectively. For choline plus betaine, the risks of incident CHD by quartiles were 1.23 (0.94, 1.61), 1.22 (0.89, 1.66) and 1.50 (1.00, 2.26), respectively. We adjusted for all the variables included in the models #3 (table ).