Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial.

BACKGROUND: Choline is a dietary precursor to the gut microbial generation of the prothrombotic and proatherogenic metabolite trimethylamine-N-oxide (TMAO). Eggs are rich in choline, yet the impact of habitual egg consumption on TMAO levels and platelet function in human subjects remains unclear. METHODS: Healthy volunteers (41% male, 81% Caucasian, median age 28 years) with normal renal function (estimated glomerular filtration rate >60) were recruited and assigned to 1 of 5 daily interventions for 4 weeks: 1) hardboiled eggs (n = 18); 2) choline bitartrate supplements (n = 20); 3) hardboiled eggs + choline bitartrate supplements (n = 16); 4) egg whites + choline bitartrate supplements (n = 18); 5) phosphatidylcholine supplements (n = 10). Fasting blood and urine samples were collected for quantification of TMAO, its precursors, and platelet aggregometry. RESULTS: Participants' plasma TMAO levels increased significantly in all 3 intervention arms containing choline bitartrate (all P < .0001), but daily ingestion of 4 large eggs (P = .28) or phosphatidylcholine supplements (P = .27) failed to increase plasma TMAO levels. Platelet reactivity also significantly increased in the 3 intervention arms containing choline bitartrate (all P < .01), but not with eggs (P = .10) or phosphatidylcholine supplements (P = .79). CONCLUSIONS: Despite high choline content in egg yolks, healthy participants consuming 4 eggs daily showed no significant increase in TMAO or platelet reactivity. However, choline bitartrate supplements providing comparable total choline raised both TMAO and platelet reactivity, demonstrating that the form and source of dietary choline differentially contributes to systemic TMAO levels and platelet responsiveness.

Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension.

BACKGROUND: Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. METHODS: We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. RESULTS: In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ±â€¯3 versus 36.6 ±â€¯3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). CONCLUSION: While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

Lamin A/C Cardiomyopathies: Current Understanding and Novel Treatment Strategies.

OPINION STATEMENT: Dilated cardiomyopathy (DCM) is the third leading cause of heart failure in the USA. A major gene associated with DCM with cardiac conduction system disease is lamin A/C (LMNA) gene. Lamins are type V filaments that serve a variety of roles, including nuclear structure support, DNA repair, cell signaling pathway mediation, and chromatin organization. In 1999, LMNA was found responsible for Emery-Dreifuss muscular dystrophy (EDMD) and, since then, has been found in association with a wide spectrum of diseases termed laminopathies, including LMNA cardiomyopathy. Patients with LMNA mutations have a poor prognosis and a higher risk for sudden cardiac death, along with other cardiac effects like dysrhythmias, development of congestive heart failure, and potential need of a pacemaker or ICD. As of now, there is no specific treatment for laminopathies, including LMNA cardiomyopathy, because the mechanism of LMNA mutations in humans is still unclear. This review discusses LMNA mutations and how they relate to DCM, the necessity for further investigation to better understand LMNA mutations, and potential treatment options ranging from clinical and therapeutic to cellular and molecular techniques.

Targeting the Microbiome in Heart Failure.

OPINION STATEMENT: Heart failure is the leading cause of mortality and morbidity in the world today. While there have been major advances in our understanding of the pathophysiology of heart failure over the past decades, disease progression remains inevitable in the majority of patients and effective therapies to prevent heart failure are still lacking. Research has turned to better understand the gut microbiome because alterations in their ecosystems have been associated with various downstream chronic conditions including cardiovascular diseases. The gut microbiome is complex and diverse in nature, making it difficult to generalize to specific populations or individual patients. Nevertheless, current evidence has found links between heart failure and alterations in microbial composition and function, since heart failure has long been associated with impaired intestinal barrier function and bacterial translocation leading to inflammatory and immune responses. Recent studies have also shed light on the contributions of gut microbiota-derived metabolites from dietary nutrients that can promote adverse effects in the setting of cardiorenal diseases. In this review, we will discuss the role of gut microbiome in the setting of heart failure and potential interventional approaches that may potentially lower the risk of disease progression in heart failure.