Metabolomic Profiles, Ideal Cardiovascular Health, and Risk of Heart Failure and Atrial Fibrillation: Insights From the Framingham Heart Study

Abstract

Background The American Heart Association's framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). Methods and Results We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole‐3‐proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable‐adjusted models. Conclusions Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.

The Association of Metabolomic Profiles of a Healthy Lifestyle with Heart Failure Risk in a Prospective Study

“…Metabolomics provides a new insight into risk factors and CVD development. There has been research based on the Framingham Heart Study showing that glycerolipid metabolism mediated the association of the cardiovascular health (CVH) score with HF [35]. To our knowledge, we are the first to explain the association of the incident of heart failure with healthy lifestyle-related metabolic profiling.…”

The incidence and impact of atrial fibrillation on hospitalized Coronavirus disease‐2019 patients

“… 19 DM and hyperlipidemia contribute to atrial remodeling and pro‐inflammatory changes in the atrial tissue, fostering the development and persistence of AF. 20 , 21 Additionally, CKD has also been found related to a higher incidence of AF due to fluid‐electrolyte imbalances, inflammation, and oxidative stress. 22 CKD is an independent predictor of severe outcomes in COVID‐19 patients, contributing to the higher rate of mortality and complications in COVID‐AF group.…”

Beat-to-beat alterations of acoustic intensity and frequency at the maximum power of heart sounds are associated with NT-proBNP levels

“…HF and AF also frequently coexist. AF precedes and follows HF with both preserved and reduced EF ( 40 ). A previous study also reported that AF is highly predictive of underlying HFpEF ( 41 ).…”