Association of Trimethylamine <i>N</i>-Oxide and Metabolites With Mortality in Older Adults

Fretts, Amanda M.; Hazen, Stanley L.; Jensen, Paul N.; Budoff, Matthew J.; Sitlani, Colleen M.; Wang, Meng; Otto, Marcia C. de Oliveira; DiDonato, Joseph A.; Lee, Yujin; Psaty, Bruce M.; Siscovick, David S.; Sotoodehnia, Nona; Tang, W.H. Wilson; Lai, Heidi; Lemaître, Rozenn N.; Mozaffarian, Dariush

doi:10.1001/jamanetworkopen.2022.13242

Cited by 27 publications

(12 citation statements)

References 40 publications

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“…Similarly, also in CHS, Fretts et al. [ 50 ] reported significant interaction by eGFR in analysis of TMAO with respect to all-cause mortality, with positive associations limited to individuals with lower eGFR (45 mL/min/1.73 m 2 ). CHS participants were aged ≥65 y at baseline, which may account for the lower eGFR ranges available for analysis.…”

Section: Discussionmentioning

confidence: 86%

“…Fretts et al. [ 50 ] included choline in their analysis of total mortality in CHS, finding a positive association between choline and all-cause mortality restricted to lower eGFR. In CARDIA, we observed a similar interaction between choline and eGFR with CVD risk, with choline positively associated at lower eGFR, but this finding was not statistically significant in analysis that additionally adjusted for TMAO and betaine.…”

Section: Discussionmentioning

confidence: 99%

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Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Shea,

Jacobs,

Howard

et al. 2024

The American Journal of Clinical Nutrition

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Shea,

Jacobs,

Howard

et al. 2024

The American Journal of Clinical Nutrition

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“…TMAO production is primarily metabolized by the intestinal microbiota, 11 and the plasma concentration of TMAO varies depending on the type of intestinal microbiota 12 . Moreover, TMAO enhances platelet activation, 13 and elevated levels are associated with an increased risk of death, myocardial infarction, and stroke 11,12,14 . However, the characteristics of the intestinal microbiota of patients with constipation and/or atherosclerotic disease have varied considerably in different studies.…”

Section: Discussionmentioning

confidence: 99%

“… 12 Moreover, TMAO enhances platelet activation, 13 and elevated levels are associated with an increased risk of death, myocardial infarction, and stroke. 11 , 12 , 14 However, the characteristics of the intestinal microbiota of patients with constipation and/or atherosclerotic disease have varied considerably in different studies. Therefore, the relationship between constipation and atherosclerosis via intestinal microbiota has not been clearly established.…”

Section: Discussionmentioning

confidence: 99%

Effect of constipation on readmission for heart failure in patients with acute heart failure

Namiuchi,

Tanita,

Sunamura

et al. 2023

ESC Heart Failure

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AimsConstipation is a common gastrointestinal disorder that is associated with a high cardiovascular event rate in the general population. Although constipation is common in patients with cardiovascular diseases, only a few studies have examined the relationship between constipation and the prognosis of patients with heart failure. This study aimed to evaluate the effects of constipation on the prognosis of patients with acute heart failure.Methods and resultsWe investigated 397 patients admitted to our hospital from December 2020 to December 2022 with acute heart failure (mean age, 81 ± 13 years; 54% men). Patients with constipation were defined as those either taking laxatives regularly or diagnosed with constipation according to the International Statistical Classification of Diseases and Related Health Problems. During the follow‐up periods (median, 173 days), 35 patients died, and 74 experienced readmission due to heart failure. Kaplan–Meier analysis before and after propensity score matching using 14 variables revealed that the risk of readmission due to heart failure was significantly higher in patients with constipation than in those without (before: log‐rank P = 0.014, after: log‐rank P = 0.0027). The adjusted Cox proportional hazards analysis revealed that the hazard ratio for readmission due to heart failure was 2.61 (95% confidence interval, 1.38–4.94, P = 0.0032). The risk of all‐cause death was not significantly different between the two groups (hazard ratio, 1.76; 95% confidence interval, 0.61–5.06; P = 0.30).ConclusionsConstipation status was strongly associated with a higher risk of readmission for heart failure in patients with acute heart failure.

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“…Nonetheless, there are contradictory results concerning colorectal cancer, with some studies revealing negative [ 11 ] or no significant relationships [ 12 ]. Elevated levels of plasma choline have been positively correlated with increased mortality risk among older adults in the United States [ 13 ] and among Chinese adults with hypertension [ 14 ]. Moreover, differences in all-cause mortality linked to total choline consumption have been detected among various racial and ethnic groups, including black and white Americans as well as Chinese adults [ 15 ].…”

Section: Introduction/backgroundmentioning

confidence: 99%

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality

Jieru,

Zhang,

Cai

et al. 2024

J Health Popul Nutr

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Background Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. Methods This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. Results In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60–0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. Conclusion Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

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Association of Trimethylamine N-Oxide and Metabolites With Mortality in Older Adults

Cited by 27 publications

References 40 publications

Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Effect of constipation on readmission for heart failure in patients with acute heart failure

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality

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