Introduction Trimethylamine-N-oxide (TMAO) is a circulating biomarker associated with cardiovascular disease (CVD). Production of TMAO is facilitated by gut microbiota and dependent on micronutrients such as choline, betaine, and L-carnitine, present in foods such as red meat and eggs. Hypothesis We sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD using clinical data via an ordinal logistic model. Methods Data from participants (n = 127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were tested (with serum TMAO quartiles as the dependent variable), and only variables with P < 0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with P < 0.10. Results Eight candidate variables were included in the final model, with only transferrin, high-density lipoprotein cholesterol (HDL-C) and race (white vs. non-white) showing significant associations with TMAO. Participants had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) odds of being in a higher TMAO quartile compared with participants in the lowest transferrin quartile. Non-white participants had 2.92 times higher odds of being in the highest TMAO quartile compared to white individuals. Participants in the second quartile of HDL-C had 2.68 times higher odds of being in a higher TMAO quartile compared with participants in the lowest HDL-C quartile. Conclusions Transferrin demonstrated a significant predictive association with TMAO and may represent a novel potential biomarker of increased CVD risk worthy of further study. These results warrant further examination of iron, metabolism, homeostasis, and gut microbiome to better understand and mitigate known increased CVD risk.

Introduction: Trimethylamine-N-oxide (TMAO) is a circulating biomarker associated with cardiovascular disease (CVD). Production of TMAO is facilitated by gut microbiota and dependent on micronutrients such as choline, betaine, and L-carnitine, present in foods such as red meat and eggs.Hypothesis: We sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD using clinical data via an ordinal logistic model.Methods: Data from participants (n=127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were tested (with serum TMAO quartiles as the dependent variable), and only variables with P < 0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with P < 0.10.Results: Eight candidate variables were included in the final model, with only transferrin, high-density lipoprotein cholesterol (HDL-C) and race (White vs non-white) showing significant associations with TMAO. Participants had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) odds of being in a higher TMAO quartile compared with participants in the lowest transferrin quartile. Non-white participants had 2.92 times higher odds of being in the highest TMAO quartile compared to white individuals. Participants in the second quartile of HDL-C had 2.68 times higher odds of being in a higher TMAO quartile compared with participants in the lowest HDL-C quartile.Conclusions: Transferrin demonstrated a significant predictive association with TMAO and may represent a novel potential biomarker of increased CVD risk worthy of further study. These results warrant further examination of iron, metabolism, homeostasis, and gut microbiome to better understand and mitigate known increased CVD risk.

Introduction: Trimethlamine-N-oxide (TMAO) is a circulating biomarker associated with atherosclerotic cardiovascular disease (CVD) risk and results from metabolism of micronutrients choline and L-carnitine, present in foods such as red meat and eggs. Hypothesis: The investigators sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD, using clinical and dietary consumption data via an ordinal logistic model. Methods: Data from patients (n=127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were run (with serum TMAO quartiles as the dependent variable), and only variables with p <0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with p <0.10. Results: Eight candidate variables were included in the final model, with only transferrin and HDL cholesterol with significant associations with TMAO (Table) . Patients had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) times the odds to be in a higher TMAO quartile compared with patients in the lowest transferrin quartile. Patients in the second quartile of HDL had 2.68 times higher odds to be in a higher TMAO quartile compared with patients in the lowest HDL quartile. Non-Whites had 2.92 times higher odds of being in the highest TMAO quartile as compared to whites in this cohort. Conclusions: Transferrin showed the strongest association with TMAO; thus, transferrin may represent a novel potential biomarker of increased CVD risk worthy of further study.