Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

Abstract

The predictive value of traditional cardiovascular risk estimators is limited, and young and elderly populations are particularly underrepresented. We aimed to investigate the urine metabolome and its association with cardiovascular risk to identify novel markers that might complement current estimators based on age. Urine samples were collected from 234 subjects categorized into three age-grouped cohorts: 30–50 years (cohort I, young), 50–70 years (cohort II, middle-aged), and > 70 years (cohort III, elderly). Each cohort was further classified into three groups: (a) control, (b) individuals with cardiovascular risk factors, and (c) those who had a previous cardiovascular event. Novel urinary metabolites linked to cardiovascular risk were identified by nuclear magnetic resonance in cohort I and then evaluated by target mass spectrometry quantification in all cohorts. A previously identified metabolic fingerprint associated with atherosclerosis was also analyzed and its potential risk estimation investigated in the three aged cohorts. Three different metabolic signatures were identified according to age: 2-hydroxybutyrate, gamma-aminobutyric acid, hypoxanthine, guanidoacetate, oxaloacetate, and serine in young adults; citrate, cyclohexanol, glutamine, lysine, pantothenate, pipecolate, threonine, and tyramine shared by middle-aged and elderly adults; and trimethylamine N-oxide and glucuronate associated with cardiovascular risk in all three cohorts. The urinary metabolome contains a metabolic signature of cardiovascular risk that differs across age groups. These signatures might serve to complement existing algorithms and improve the accuracy of cardiovascular risk prediction for personalized prevention. Key messages • Cardiovascular risk in the young and elderly is underestimated. • The urinary metabolome reflects cardiovascular risk across all age groups. • Six metabolites constitute a metabolic signature of cardiovascular risk in young adults. • Middle-aged and elderly adults share a cardiovascular risk metabolic signature. • TMAO and glucuronate levels reflect cardiovascular risk across all age groups.

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

“…Glutamine was here found decreased in both biological fluids from cardiovascular risk patients, and also in the secretome of VSMCs pointing to a deleterious protective effect against atherosclerosis development. These data are in consonance with our previously reported diminished levels in urine from middle age (50-70 years) and elderly (>70 years) subjects with cardiovascular risk factors [22].…”

“…In our study, secreted TMAO levels increase in response to a pro-inflammatory stimulus in what can be seen as a contribution to observed higher levels in plasma and urine from cardiovascular risk subjects with moderately preserved renal function. Urinary TMAO was found increased in young (30-50 years), middle age (50-70 years) and elderly (>70 years) population with cardiovascular risk factors in our previous study [22], in agreement with data shown here and pointing to a strong association with CV risk independently of age.…”

“…Choline is a structural component of cell membranes; it participates in the transport and metabolism of cholesterol and helps maintaining circulating homocysteine levels. Increased plasma homocysteine is an independent risk factor for atherosclerosis development which can be caused by decreased methylation of homocysteine to form methionine, being choline the methyl donor [ 22 ]. Our data support a role for choline in the increased cardiovascular risk associated with circulating homocysteine.…”

Contribution of Multiplex Immunoassays to Rheumatoid Arthritis Management: From Biomarker Discovery to Personalized Medicine

“…The advancement of proteomic techniques in the last two decades has allowed the identification of a large number of candidate proteins that can act as potential biomarkers for several diseases [101][102][103][104][105][106]. This development in particular shows promise for the treatment of highly prevalent disorders, such as cardiovascular disease or cancer, in which early diagnosis is currently impeded by the absence of adequate diagnostic biomarkers.…”

Urinary Spermidine Predicts and Associates with In-Hospital Acute Kidney Injury after Cardiac Surgery

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