Using urinary metabolomics to identify metabolic pathways linked to cardiac structural alterations in young adults: The African-PREDICT study

Background and aims: Risk factor exposure from young ages was shown to contribute to cardiovascular events -cardiac hypertrophy, which may be accompanied by an altered meta-bolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors.Methods and results: We included healthy adults (N = 1202), aged 20-30 years, stratified based on risk factors, i.e., obesity, physical inactivity, elevated blood pressure (BP), hyperglycemia, dys-lipidemia, low socio-economic status, smoking and excessive alcohol use -forming the CVD risk group (N = 1036) and the control group (N = 166). Relative wall thickness (RWT) and left ven-tricular mass index (LVMi) were measured using echocardiography. Targeted metabolomics data were obtained using a liquid chromatography-tandem mass spectrometry method. Clinic systolic BP, 24 h BP and RWT were higher in the CVD risk group compared to the control group (all P & LE; 0.031). Exclusively in the CVD risk group, RWT associated with creatine and dodecanoylcar-nitine; while LVMi associated with glycine, serine, glutamine, threonine, alanine, citrulline, cre-atine, proline, pyroglutamic acid and glutamic acid (all P & LE; 0.040). Exclusively in the control group, LVMi associated with propionylcarnitine and butyrylcarnitine (all P & LE; 0.009).Conclusion: In young adults without CVD, but with CVD risk factors, LVMi and RWT associated with metabolites linked energy metabolism (shifting from solely fatty acid oxidation to glycol-ysis, with impaired creatine kinase activity) and oxidative stress. Our findings support early onset metabolic changes accompanying cardiac structural alterations due to lifestyle and behavioural risk factors.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).