Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings

Abstract

Metabolomics, the comprehensive measurement of low-molecular-weight molecules in biological fluids used for metabolic phenotyping, has emerged as a promising tool to better understand pathways underlying cardiovascular disease (CVD) and to improve cardiovascular risk stratification. Here, we present the main methodologies for metabolic phenotyping, the methodological steps to analyse these data in epidemiological settings and the associated challenges. We discuss evidence from epidemiological studies linking metabolites to coronary heart disease and stroke. These studies indicate the systemic nature of CVD and identify associated metabolic pathways such as gut microbial cometabolism, branched-chain amino acids, glycerophospholipid and cholesterol metabolism, as well as activation of inflammatory processes. Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation. The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established. As sample sizes with high-dimensional molecular data increase in epidemiological settings, integration of metabolomic data across studies and platforms with other molecular data will lead to new understanding of the metabolic processes underlying CVD and contribute to identification of potentially novel preventive and pharmacological targets. Metabolic phenotyping offers a powerful tool in the characterisation of the molecular signatures of CVD, paving the way to new mechanistic understanding and therapies, as well as improving risk prediction of CVD patients. However, there are still challenges to face in order to contribute to clinically important improvements in CVD.

Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

“…Moreover, some of the metabolites have potential to be biomarkers (i.e., screening, diagnostic, or prognostic biomarkers). Metabolomics have been comprehensively applied in studying CVD in the general population and CVD cohorts [ 119 , 120 ]. Table 4 summarizes metabolomics studies in CVD in people with diabetes [ 95 , 107 , 112 , 121 , 122 , 123 , 124 , 125 , 126 , 127 ].…”

Exploring functional metabolites in preterm infants

“…Urine is a downstream sample in comparison and includes more water soluble and metabolic by products 28 . Because urine contains concentrated waste products of many metabolic processes that give insight into the underlying metabolic activity, it is possible to analyse a large number of compounds 25,30 …”

“…28 Because urine contains concentrated waste products of many metabolic processes that give insight into the underlying metabolic activity, it is possible to analyse a large number of compounds. 25,30 For neonatal practice, non-invasive techniques are used to collect the urine samples, where a sterile ball of cotton is placed into the nappy/diaper and absorbed urine is transferred with a sterile syringe into a sterile cryovial. 10,25 Stool sample collection in neonatal practice uses sterile sampling spoons to directly transfer the sample from the infants nappy/diaper into sterile sample containers.…”

Metabolic and Metabolomics Insights into Dilated Cardiomyopathy

“…Over the last decade, many metabolomics reviews have focused on the broader cardiovascular disease (CVD) [19, 23, 24] rather than specific CVDs such as DCM. This review sought to examine the literature to present evidence of metabolic changes in DCM and possible mechanisms behind these alterations.…”